Online first articles (not assigned to a volume)
- L. Søfteland, M. Berntssen, J. Kirwan, T. Størseth, M. Viant, B. Torstensen, R. Waagbø, P. OlsvikCollection of Toxicology Reports (1970).
Abstract
Extended use of plant ingredients in Atlantic salmon farming has increased the need for knowledge on the effects of new nutrients and contaminants in plant based feeds on fish health and nutrient-contaminant interactions. Primary Atlantic salmon hepatocytes were exposed to a mixture of PAHs and pesticides alone or in combination with the nutrients ARA, EPA, α-tocopherol, and γ-tocopherol according to a factorial design. Cells were screened for effects using xCELLigence cytotoxicity screening, NMR spectroscopy metabolomics, mass spectrometry lipidomics and RT-qPCR transcriptomics. The cytotoxicity results suggest that adverse effects of the contaminants can be counteracted by the nutrients. The lipidomics suggested effects on cell membrane stability and vitamin D metabolism after contaminant and fatty acid exposure. Co-exposure of the contaminants with EPA or α-tocopherol contributed to an antagonistic effect in exposed cells, with reduced effects on the VTG and FABP4 transcripts. ARA and γ-tocopherol strengthened the contaminant-induced response, ARA by contributing to an additive and synergistic induction of CYP1A, CYP3A and CPT2, and γ-tocopherol by synergistically increasing ACOX1. Individually EPA and α-tocopherol seemed more beneficial than ARA and γ-tocopherol in preventing the adverse effects induced by the contaminant mixture, though a combination of all nutrients showed the greatest ameliorating effect.Abstract
Extended use of plant ingredients in Atlantic salmon farming has increased the need for knowledge on the effects of new nutrients and contaminants in plant based feeds on [...]
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- A. Sani, M. IdrisCollection of Toxicology Reports (2017).
Abstract
The constant discharge of agricultural waste into aquatic environment has led to accumulation of heavy chemicals and other variety of pollutants. Herbicides present in these wastes are washed down, carried by rains and flood to nearby aquatic environment. Glyphosate is one of the most popular herbicides used by farmers in Kano because of its active reaction on killing weeds without affecting the crops. A toxicity test of glyphosate was conducted using concentrations of 0, 0.004, 0.005, 0.006, 0.007 ml/l. The mortality rate of each concentration was determined and the physicochemical parameters (Dissolved oxygen and pH) were also determined. The result showed that high mortality occurs at 0.007 ml/l and less mortality was found at 0.004 ml/l. Hence, mortality is dose dependent. DO and pH decreases with increase in glyphosate concentration. Furthermore, the juveniles showed abnormal behaviour. The LC50 value at 96 h was 0.0072 ml/l. There was significant difference between the initial and final pH value (p < 0.05). On the other hand, the initial and final DO values showed no significant difference (p > 0.05). However, correlation between DO and pH showed no significant difference (p > 0.05). The findings of this study established that glyphosate has some level of toxicity on Clarias gariepinus juveniles. In addition, it was found that mortality, changes in behaviour, DO and pH are dose dependent. Therefore, it was suggested that an appropriate concentration that will not be detrimental to non-target organisms should be used by farmers. Alternatively, Biological method should be used as a substitute for chemical method of controlling weeds.Abstract
The constant discharge of agricultural waste into aquatic environment has led to accumulation of heavy chemicals and other variety of pollutants. Herbicides present in these [...]- 0
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- W. Klaren, S. Flor, K. Gibson-Corley, G. Ludewig, L. RobertsonCollection of Toxicology Reports (2017).
Abstract
Polychlorinated biphenyls (PCBs), industrial chemicals and persistent environmental pollutants, are found in rural and urban settings. Rodent studies have shown that exposure to PCB126, a dioxin-like PCB, causes a significant disruption of hepatic micronutrient homeostasis and an increase in metallothionein (MT), an antioxidant protein and metal carrier. A MT knockout mouse strain was used to assess metallothionein’s role in micronutrient disruption and overall hepatotoxicity. Twenty four 129S male mice (12 wild type (WT) and 12 MT knockout (MTKO)) were placed on a purified diet (AIN-93G) for 3 weeks to achieve hepatic metal equilibrium. Mice were then given a single IP injection of either vehicle or 150 μmol/kg PCB126 in vehicle. The animals were sacrificed 2 weeks later and organs processed for analysis. Liver histology, hepatic lipids, gene expression, micronutrient and ROS status were investigated. Liver weights, liver lipids, ROS, and hepatocyte vacuolation were increased with PCB126 exposure along with AhR responsive genes. The MTKO animals had more severe histological changes in the liver and elevated liver lipids than their wild type counterparts. Hepatic and renal metals levels (Cu, Zn, Se and Mn) were mostly reduced by PCB126 treatment. Renal micronutrients were more affected by PCB126 treatment in the MTKO animals. This research suggests that MT may not be the sole/primary cause of the metal disruption caused by PCB126 exposure in mice, but may provide protection against overall hepatotoxicity.Abstract
Polychlorinated biphenyls (PCBs), industrial chemicals and persistent environmental pollutants, are found in rural and urban settings. Rodent studies have shown that exposure [...]- 0
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- D. Karanewsky, A. Arthur, H. Liu, B. Chi, L. Ida, S. MarkisonCollection of Toxicology Reports (2017).
Abstract
A toxicological evaluation of a umami flavour compound, 2-(((3-(2, 3-dimethoxyphenyl)-1H -1, 2, 4-triazol-5-yl)thio)methyl)pyridine (S3643, CAS 902136-79-2), was completed for the purpose of assessing its safety for use in food and beverage applications. S3643 undergoes extensive oxidative metabolism in vitro with rat microsomes producing the S3643-sulfoxide and 4′-hydroxy-S3643 as the major metabolites. In incubations with human microsomes, the O -demethyl-S3643 and S3643-sulfoxide were produced as the major metabolites. In pharmacokinetic studies in rats, the S3643-sulfoxide represents the dominant biotransformation product. S3643 was not found to be mutagenic or clastogenic in vitro, and did not induce micronuclei in CHO-WBL cells. In subchronic oral toxicity studies in rats, the no-observed-adverse-effect-level (NOAEL) for S3643 was 100 mg/kg bw/day (highest dose tested) when administered in the diet for 90 consecutive days.Abstract
A toxicological evaluation of a umami flavour compound, 2-(((3-(2, 3-dimethoxyphenyl)-1H -1, 2, 4-triazol-5-yl)thio)methyl)pyridine (S3643, CAS 902136-79-2), was completed [...]- 0
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- C. Iwegbue, F. Bassey, G. Obi, G. Tesi, B. MartincighCollection of Toxicology Reports (2017).
Abstract
The concentrations of nine metals (Cd, Pb, Ni, Cr, Co, Cu, Fe, Mn and Zn) were determined in lip sticks, lip glosses, lip balms, eye pencils, eyeliners, eye shadows, blushes, mascaras and face powders. The study was aimed at providing information on the risk associated with human exposure to metals in these facial cosmetic products. The concentrations of metals in the samples were measured by atomic absorption spectrometry after digestion with a mixture of nitric acid, hydrochloric acid and hydrogen peroxide. The mean concentrations of metals in these facial cosmetics ranged from 3.1 to 8.4 μg g−1 Cd, 12–240 μg g−1 Pb, 9.1–44 μg g−1 Cr, 18–288 μg g−1 Ni, 1.6–80 μg g−1 Cu, 7.9–17 μg g−1 Co, 2.3–28 mg g−1 Fe, 12–230 μg g−1 Mn, and from 18 to 320 μg g−1 Zn. The concentrations of Ni, Cr and Co were above the suggested safe limit of 1 μg g−1 for skin protection, while Cd and Pb were above the Canadian specified limits. The systemic exposure dosage (SED) values for these metals obtained from the use of these facial cosmetic products were below their respective provisional tolerable daily intake (PTDI)/or recommended daily intake (RDI) values. The margin of safety values obtained were greater than 100 which indicated that the concentrations of the metals investigated in these facial cosmetics do not present considerable risk to the users except in the case of face powders.Abstract
The concentrations of nine metals (Cd, Pb, Ni, Cr, Co, Cu, Fe, Mn and Zn) were determined in lip sticks, lip glosses, lip balms, eye pencils, eyeliners, eye shadows, blushes, [...]- 0
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- S. Ivanović, B. Dimitrijević, V. Ćupić, M. Jezdimirović, S. Borozan, M. Savić, D. SavićCollection of Toxicology Reports (2017).
Abstract
Diazinon (DZN) is an organophosphate insecticide which exerts its effect through the inhibition of acetylcholinesterase enzyme (AChE). In this work, we studied the development of tolerance to subchronic p.o. administration of DZN in rats, under both in vivo and in vitro conditions. A group of 20 rats (2 groups, n = 10) was administered p.o. the 1/10 of established LD50 DZN (namely 55.87 mg/kg bw) for 28 days. On the 14th and 28th day of study with isolated diaphragm and ileum, we examined the downregulation of nicotinic and muscarinic receptor function through Electrical Field Stimulation (EFS). Maximum contractility of the diaphragm was recorded on the 14th day of the study (25% higher compared to the non-treated rats), while on the 28th day the contractions almost did not differ from the values found in non-treated rats. EFS of isolated ileum on the 14th day of study caused significantly higher contractions compared to the non-treated rats, but after 28 days, ileum contractions decreased approximately to the level of contractions in non-treated rats. On the 14th study day, we also recorded increased amplitude of spontaneous ileum contractions, compared to non-treated rats. The application of increasing ACh concentrations caused dose-dependent ileum contractions, without statistically significant differences of median effective concentration (EC50 ) values in non-treated and treated rats. Tolerance to subchronic DZN administration develops due to various adaptation mechanisms, including the most important one—downregulation of nicotinic and muscarinic receptor function.Abstract
Diazinon (DZN) is an organophosphate insecticide which exerts its effect through the inhibition of acetylcholinesterase enzyme (AChE). In this work, we studied the development [...]- 0
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- F. Solmaz, E. Gündoğdu, D. Akduman, M. Haksever, O. Dikici, F. ÜnalCollection of Toxicology Reports (2017).
Abstract
Aminoglycosides (AGs) have been widely used for potential life-threatening bacterial infections. Although AGs are well known for their ototoxic side effects, some AGs such as amikacin are considered less harmful to auditory functions, thus, auditory monitoring is mostly neglected during treatment with these drugs. To reflect the potential auditory hazards of repeated amikacin use on the patients with cystic fibrosis (CF). 32CF patients with prior exposure to at least 3 courses of amikacin (the CF group) and 35 non-CF patients visiting the outpatient clinic with any complaint other than hearing loss and no history of treatment with any AG(the control, or C group) were compared with pure-tone audiometry(PTA). The diagnosis of CF was made by Nanoduck sweat test. The average age of the participants were 8.25 ± 2.76 years in the CF group and 8.58 ± 2.00 years in the C group (ranging from 5 to 13 years). 29 (43.28%) of the cases were female and 38 (56.71%) were male. Clinical SNHL(sensorineural hearing loss) was detected in 4 of the 32 subjects in the CF group. None of the subjects in the C group exhibited clinical SNHL. There was no statistically significant difference between the groups with regard to presence or absence of clinical SNHL (p > 0.05). However, hearing levels of the CF group were around 20 dB(decibel) HL(hearing loss), whereas hearing levels of the C group were around 5 dB. This difference was statistically significant for the pure tone averages of both all frequencies and speech frequencies (p < 0.05). Repetitive exposure to AGs can cause permanent, although mild, sensorineural hearing loss. For prevention, hearing status of the patient should be closely monitored and treatment of choice should be precisely tailored according to the audiological evaluation. This is especially important in patients with CF who frequently experience medical conditions necessitating AGs use.Abstract
Aminoglycosides (AGs) have been widely used for potential life-threatening bacterial infections. Although AGs are well known for their ototoxic side effects, some AGs such [...]- 0
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- D. Monte, J. Tenório, I. Bastos, F. Mendonça, J. Neto, T. Silva, C. RamosCollection of Toxicology Reports (2017).
Abstract
Considering the increase in consumption of Cannabis sativa and the use of the compound β- carotene (BC) as supplement, we investigated potential changes in the chemical and biological proprieties of BC after exposure to C. sativa smoke (CSS). Our results showed that the BC exposed to CSS underwent 98.8% degradation and suffered loss of its antiradical activity. The major degradation products identified were 3-hydroxy-2, 4, 4-trimethylpentyl)2-methylpropanoate and (2-ethyl-3-hydroxyhexyl)2-methylpropanoate compounds. These are found in higher levels in the exhalations of colorectal cancer patients and are similar to the toxic products associated with lipid peroxidation of polyunsaturated fatty acids. In toxicological assays using micro-crustacean Artemia salina the BC was non-toxic, while the BC degraded by CSS had a toxicity of LC50 = 397.35 μg/mL. In Wistar rats, females treated with BC degraded by CSS (BCCSS) showed whitish liver spots, alterations in liver weight and in bilirubin and alkaline phosphatase levels, and decrease in the number of leukocytes associated with atypical lymphocytosis. In male rats, there was an increase in the number of leukocytes when compared to the control group. In the histopathological analysis, the cortical region of the kidneys showed the presence of discrete amorphous eosinophilic material (cylinders) in the lumen of the proximate and distal convoluted tubules. In general, the BC in contact with CSS undergoes chemical changes and exhibits toxicity to rats and Artemia salina .Abstract
Considering the increase in consumption of Cannabis sativa and the use of the compound β- carotene (BC) as supplement, we investigated potential changes in the chemical and [...]- 0
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- C. Bastos, P. Ávila, E. Filho, R. Ávila, A. Batista, S. Fonseca, E. Lima, R. Marreto, E. Mendonça, M. ValadaresCollection of Toxicology Reports (2017).
Abstract
Several studies towards the development of an effective treatment for intestinal mucositis have been reported, since this condition represents a major problem in clinical oncology practice due to cytotoxic effects of chemotherapy. However standardized protocols and universally accepted treatment options are yet to be established. Given above, this study evaluated the protective effects of a mucoadhesive formulation containing both Bidens pilosa L. (Asteraceae) (BP) and curcuminoids from Curcuma longa L. (Zingiberaceae) (CL) on intestinal mucositis induced by 5-fluoruoacil (5-FU) in mice. As expected, animals only treated with 5-FU (200 mg/kg) showed a significant reduction of 60.3 and 42.4% in villi and crypts size, respectively, when compared to control. On the other hand, the proposed therapeutic/prophylactic treatment with mucoadhesive formulations managed to reduce histopathologic changes in mice bearing mucositis, especially at 125 mg/kg BP + 15 mg/kg CL dose. The formulation promoted an increase of 275.5% and 148.7% for villi and crypts size, respectively. Moreover, chemotherapy-related weight loss was reduced by 7.4% following the treatment. In addition, an increase of 10 and 30.5% in red and white blood cells was observed when compared to 5-FU group. Furthermore, treatments with the mucoadhesive formulation containing BP/CL up modulated Ki-67 and Bcl-2 expression while reduced pro-apoptotic regulator Bax. The formulation also modulated inflammatory response triggered by 5-FU through reduction of 68% of myeloperoxidase activity and a 4-fold increase in anti-inflammatory IL-10 levels. In parallel, the oxidative stress via lipid peroxidation was reduced as indicated by decrease of 63% of malondialdehyde concentrations. Additionally, the new formulation presented low acute oral systemic toxicity, being classified in the category 5 (2000 mg/kg < LD50 < 5000 mg/kg) of the Globally Harmonized Classification System. This study showed an interesting potential of the mucoadhesive formulation of BP/CL for the treatment of 5-FU-induced intestinal mucositis. Given the perspectives for the development of a new medicine, clinical studies are in progress to better understand the protective effects of this innovative formulation in treating mucositis.Abstract
Several studies towards the development of an effective treatment for intestinal mucositis have been reported, since this condition represents a major problem in clinical [...]- 0
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- R. Collí-Dulá, M. Friedman, B. Hansen, N. DenslowCollection of Toxicology Reports (2017).
Abstract
Acrylamide is known to produce follicular cell tumors of the thyroid in rats. RccHan Wistar rats were exposed in utero to a carcinogenic dose of acrylamide (3 mg/Kg bw/day) from gestation day 6 to delivery and then through their drinking water to postnatal day 35. In order to identify potential mechanisms of carcinogenesis in the thyroid glands, we used a transcriptomics approach. Thyroid glands were collected from male pups at 10 PM and female pups at 10 AM or 10 PM in order to establish whether active exposure to acrylamide influenced gene expression patterns or pathways that could be related to carcinogenesis. While all animals exposed to acrylamide showed changes in expected target pathways related to carcinogenesis such as DNA repair, DNA replication, chromosome segregation, among others, animals that were sacrificed while actively drinking acrylamide-laced water during their active period at night showed increased changes in pathways related to oxidative stress, detoxification pathways, metabolism, and activation of checkpoint pathways, among others. In addition, thyroid hormones, triiodothyronine (T3) and thyroxine (T4), were increased in acrylamide-treated rats sampled at night, but not in quiescent animals when compared to controls. The data clearly indicate that time of day for sample collection is critical to identifying molecular pathways that are altered by the exposures. These results suggest that carcinogenesis in the thyroids of acrylamide treated rats may ensue from several different mechanisms such as hormonal changes and oxidative stress and not only from direct genotoxicity, as has been assumed to date.Abstract
Acrylamide is known to produce follicular cell tumors of the thyroid in rats. RccHan Wistar rats were exposed in utero to a carcinogenic dose of acrylamide (3 mg/Kg bw/day) [...]- 0
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- C. Gao, Z. He, J. Li, X. Li, Q. Bai, Z. Zhang, X. Zhang, S. Wang, X. Xiao, F. Wang, . Yan, D. Li, L. Chen, X. Zeng, Y. Xiao, G. Dong, Y. Zheng, Q. Wang, W. ChenCollection of Toxicology Reports (2017).
Abstract
To explore whether the alteration of lncRNA expression is correlated with polycyclic aromatic hydrocarbons (PAHs) exposure and DNA damage, we examined PAHs external and internal exposure, DNA damage and lncRNAs (HOTAIR, MALAT1, TUG1 and GAS5) expression in peripheral blood lymphocytes (PBLCs) of 150 male coke oven workers and 60 non-PAHs exposure workers. We found the expression of HOTAIR, MALAT1, and TUG1 were enhanced in PBLCs of coke oven workers and positively correlated with the levels of external PAHs exposure (adjusted Ptrend < 0.001 for HOTAIR and MALAT1, adjusted Ptrend = 0.006 for TUG1). However, only HOTAIR and MALAT1 were significantly associated with the level of internal PAHs exposure (urinary 1-hydroxypyrene) with adjusted β = 0.298, P = 0.024 for HOTAIR and β = 0.090, P = 0.034 for MALAT1. In addition, the degree of DNA damage was positively associated with MALAT1 and HOTAIR expression in PBLCs of all subjects (adjusted β = 0.024, P = 0.002 for HOTAIR and β = 0.007, P = 0.003 for MALAT1). Moreover, we revealed that the global histone 3 lysine 27 trimethylation (H3K27me3) modification was positively associated with the degree of genetic damage (β = 0.061, P < 0.001) and the increase of HOTAIR expression (β = 0.385, P = 0.018). Taken together, our findings suggest that altered HOTAIR and MALAT1 expression might be involved in response to PAHs-induced DNA damage.Abstract
To explore whether the alteration of lncRNA expression is correlated with polycyclic aromatic hydrocarbons (PAHs) exposure and DNA damage, we examined PAHs external and internal [...]- 0
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- B. Ramachandran, S. Jayavelu, K. Murhekar, T. RajkumarCollection of Toxicology Reports (2017).
Abstract
EGCG (Epigallocatechin-3-gallate) is the major active principle catechin found in green tea. Skepticism regarding the safety of consuming EGCG is gaining attention, despite the fact that it is widely being touted for its potential health benefits, including anti-cancer properties. The lack of scientific data on safe dose levels of pure EGCG is of concern, while EGCG has been commonly studied as a component of GTE (Green tea extract) and not as a single active constituent. This study has been carried out to estimate the maximum tolerated non-toxic dose of pure EGCG and to identify the treatment related risk factors. In a fourteen day consecutive treatment, two different administration modalities were compared, offering an improved [i.p (intraperitoneal)] and limited [p.o (oral)] bioavailability. A trend of dose and route dependant hepatotoxicity was observed particularly with i.p treatment and EGCG increased serum lipid profile in parallel to hepatotoxicity. Fourteen day tolerable dose of EGCG was established as 21.1 mg/kg for i.p and 67.8 mg/kg for p.o. We also observed that, EGCG induced effects by both treatment routes are reversible, subsequent to an observation period for further fourteen days after cessation of treatment. It was demonstrated that the severity of EGCG induced toxicity appears to be a function of dose, route of administration and period of treatment.Abstract
EGCG (Epigallocatechin-3-gallate) is the major active principle catechin found in green tea. Skepticism regarding the safety of consuming EGCG is gaining attention, despite [...]- 0
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- L. Bain, J. Liu, R. LeagueCollection of Toxicology Reports (2017).
Abstract
Millions of people are exposed to arsenic through their drinking water and food, but the mechanisms by which it impacts embryonic development are not well understood. Arsenic exposure during embryogenesis is associated with neurodevelopmental effects, reduced weight gain, and altered locomotor activity, and in vitro data indicates that arsenic exposure inhibits stem cell differentiation. This study investigated whether arsenic disrupted the Wnt3a signaling pathway, critical in the formation of myotubes and neurons, during the differentiation in P19 mouse embryonic stem cells. Cells were exposed to 0, 0.1, or 0.5 μM arsenite, with or without exogenous Wnt3a, for up to 9 days of differentiation. Arsenic exposure alone inhibits the differentiation of stem cells into neurons and skeletal myotubes, and reduces the expression of both β-catenin and GSK3β mRNA to ∼55% of control levels. Co-culture of the arsenic-exposed cells with exogenous Wnt3a rescues the morphological phenotype, but does not alter transcript, protein, or phosphorylation status of GSK3β or β-catenin. However, arsenic exposure maintains high levels of Hes5 and decreases the expression of MASH1 by 2.2-fold, which are anti- and pro-myogenic and neurogenic genes, respectively, in the Notch signaling pathway. While rescue with exogenous Wnt3a reduced Hes5 levels, MASH1 levels stay repressed. Thus, while Wnt3a can partially rescue the inhibition of differentiation from arsenic, it does so by also modulating Notch target genes rather than only working through the canonical Wnt signaling pathway. These results indicate that arsenic alters the interplay between multiple signaling pathways, leading to reduced stem cell differentiation.Abstract
Millions of people are exposed to arsenic through their drinking water and food, but the mechanisms by which it impacts embryonic development are not well understood. Arsenic [...]- 0
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- A. Ghosh, S. Banerjee, A. Mitra, M. Muralidharan, B. Roy, R. Banerjee, A. Mandal, I. ChatterjeeCollection of Toxicology Reports (2017).
Abstract
Cigarette smoke (CS) is an important source of morbidity and early mortality worldwide. Besides causing various life-threatening diseases, CS is also known to cause hypoxia. Chronic hypoxia would induce early aging and premature death. Continuation of smoking during pregnancy is a known risk for the unborn child. Although carbon monoxide (CO) is considered to be a cause of hypoxia, the effect of other component(s) of CS on hypoxia is not known. Here we show by immunoblots and mass spectra analyses that in smoker’s blood p -benzoquinone (p -BQ) derived from CS forms covalent adducts with cysteine 93 residues in both the β chains of hemoglobin (Hb) producing Hb-p -BQ adducts. UV–vis spectra and CD spectra analyses show that upon complexation with p -BQ the structure of Hb is altered. Compared to nonsmoker’s Hb, the content of α-helix decreased significantly in smoker’s Hb (p = 0.0224). p -BQ also induces aggregation of smoker’s Hb as demonstrated by SDS-PAGE, dynamic light scattering and atomic force microscopy. Alteration of Hb structure in smoker’s blood is accompanied by reduced oxygen binding capacity. Our results provide the first proof that p -BQ is a cause of hypoxia in smokers. We also show that although both p -BQ and CO are responsible for causing hypoxia in smokers, exposure to CO further affects the function over and above that produced by Hb-p -BQ adduct.Abstract
Cigarette smoke (CS) is an important source of morbidity and early mortality worldwide. Besides causing various life-threatening diseases, CS is also known to cause hypoxia. [...]- 0
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- Y. Iizuka, H. Kim, M. Nakasatomi, T. Izawa, S. Hirako, A. MatsumotoCollection of Toxicology Reports (2017).
Abstract
Pioglitazone, a thiazolidinedione (TZD), is widely used as an insulin sensitizer in the treatment of type 2 diabetes. However, body weight gain is frequently observed in TZD-treated patients. Fish oil improves lipid metabolism dysfunction and obesity. In this study, we demonstrated suppression of body weight gain in response to pioglitazone administration by combination therapy of pioglitazone and fish oil in type 2 diabetic KK mice. Male KK mice were fed experimental diets for 8 weeks. In safflower oil (SO), safflower oil/low-dose pioglitazone (S/PL), and safflower oil/high-dose pioglitazone (S/PH) diets, 20% of calories were provided by safflower oil containing 0%, 0.006%, or 0.012% (wt/wt) pioglitazone, respectively. In fish oil (FO), fish oil/low-dose pioglitazone (F/PL), and fish oil/high-dose pioglitazone (F/PH) diets, 20% of calories were provided by a mixture of fish oil and safflower oil. Increased body weight and subcutaneous fat mass were observed in the S/PL and S/PH groups, however, diets containing fish oil were found to ameliorate these changes. Hepatic mRNA levels of lipogenic enzymes were significantly decreased in fish oil-fed groups. These findings demonstrate that the combination of pioglitazone and fish oil decreases subcutaneous fat accumulation, ameliorating pioglitazone-induced body weight gain, through fish oil-mediated inhibition of hepatic de novo lipogenesis.Abstract
Pioglitazone, a thiazolidinedione (TZD), is widely used as an insulin sensitizer in the treatment of type 2 diabetes. However, body weight gain is frequently observed in TZD-treated [...]- 0
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- M. Ramirez-Mares, H. Kobayashi, E. MejiaCollection of Toxicology Reports (2017).
Abstract
In vitro cell proliferation, cell cycle arrest and induction of apoptosis were investigated, using three human head and neck squamous cell carcinoma (HNSCC) cell lines (OSCC-3, SCC-61, and SQ-20B). Aqueous extracts of Camellia sinensis, Ilex paraguariensis, and Ardisia compressa were tested and (−) epigallocatechin-3-gallate (EGCG) was used for comparison. For EGCG the IC50 values were between 80 and 166 μM and for the extracts among 75 and 505 μM eq. (+) catechin, with C. sinensis demonstrating dominant cytotoxicity. There was not a correlation between antioxidant capacity and cytotoxicity. Flow cytometry analysis revealed similarities in response for EGCG and C. sinensis . The A. compressa extract altered DNA distribution (P < 0.05) and was the most effective in induction of apoptosis via caspases (P < 0.05). Not all HNSCC cells tested responded to the same preventive agents. The fact that A. compressa inhibits HNSCC cell proliferation makes this aqueous extract a potential source of chemopreventive agents.Abstract
In vitro cell proliferation, cell cycle arrest and induction of apoptosis were investigated, using three human head and neck squamous cell carcinoma (HNSCC) cell lines (OSCC-3, [...]- 0
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- S. Miltonprabu, . Nazimabashir, V. ManoharanCollection of Toxicology Reports (2017).
Abstract
The present study was undertaken to evaluate the possible ameliorative role of grape seed proanthocyanidins (GSP) against Cadmium (Cd) induced hepatic inflammation, apoptosis and hepatic mitochondrial toxicity in rats. Male Wistar rats were distributed in four experimental groups: control, GSP, Cd and Cd + GSP. Exposure to a hepatotoxic dose of Cd (5 mg/kg BW) caused liver damage, coupled with enhanced reactive oxygen species (ROS) generation, increased inflammation and apoptosis in liver with increased DNA damage in hepatocytes of rats. Mitochondria were isolated from the hepatic tissues of rats from each group. Our results showed significant decrease in the tri-carboxylic acid cycle enzymes, increased mitochondrial swelling, inhibition of cytochrome c oxidase activity and complex I–III, II–III and IV mediated electron transfer, decreased mitochondrial ATPases, a reduction in calcium content and mitochondrial oxygen consumption in Cd treated rats. All these molecular changes caused by Cd were alleviated by the pre-supplementation with GSP (100 mg/kg BW). The ultra structural changes in the liver also support our findings. From our results, it is clearly indicated that the free radical scavenging, metal chelating and antioxidant potentials of GSP might be the possible reason, responsible for the rescue action against Cd induced mitochondrial damage in the liver of rats.Abstract
The present study was undertaken to evaluate the possible ameliorative role of grape seed proanthocyanidins (GSP) against Cadmium (Cd) induced hepatic inflammation, apoptosis [...]- 0
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- S. SarkhelCollection of Toxicology Reports (2017).
Abstract
Quillaja saponaria bark contains a high percentage of triterpene saponins and has been used for centuries as antiinflammatory and analgesic agent in Chilean folk medicine. In the Present study the anti-inflammatory activities of the aqueous extract of commercially partially purified saponin from Quillaja saponari a Mol. in in vivo animal models. Aqueous extract of the plant material was prepared by cold maceration. The anti-inflammatory activity of a commercial Quillaja saponaria Mol. (QS) saponin extract was investigated by carragenan induced mice paw edema model for acute inflammation (Winter, 1962) [16] . The anti-inflammatory activity was evaluated by carragenan in paw edema model in swiss albino mice (18–20 g). The anti-inflammatory activity was found to be dose dependent in carragenan induced paw edema. QS was found to significantly (p < 0.05) reduce the carragenan induced mice paw edema (38.59%, 20 mg/kg bw) as compared to carragenan control. The percentage inhibition of standard anti-inflammatory drug indomethacin was (55%, 10 mg/kg, bw). The results of the present study demonstrate that the aqueous extract of Quillaja saponaria saponins (QS) possess significant anti-inflammatory activity.Abstract
Quillaja saponaria bark contains a high percentage of triterpene saponins and has been used for centuries as antiinflammatory and analgesic agent in Chilean folk medicine. [...]- 0
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- T. Sarkar, M. Alam, N. Parvin, Z. Fardous, A. Chowdhury, S. Hossain, M. Haque, N. BiswasCollection of Toxicology Reports (2017).
Abstract
This study is aimed to assess the heavy metals contamination and health risk in Shrimp (Macrobrachium rosenbergii and Penaeus monodon ) collected from Khulna-Satkhira region in Bangladesh. The results showed that the Pb concentrations (0.52–1.16 mg/kg) in all shrimp samples of farms were higher than the recommended limit. The Cd levels (0.05–0.13 mg/kg) in all samples and Cr levels in all farms except tissue content at Satkhira farm were higher than the permissible limits. The individual concentration of Pb, Cd, and Cr between shrimp tissue and shell in all rivers and farms were not statistically significant (P > 0.05). Target hazard quotient (THQ) and hazard index (HI) were estimated to assess the non-carcinogenic health risks. Shrimp samples from all locations under the current study were found to be safe for consumption, the possibility of health risk associated with non-carcinogenic effect is very low for continuous consumption for 30 years.Abstract
This study is aimed to assess the heavy metals contamination and health risk in Shrimp (Macrobrachium rosenbergii and Penaeus monodon ) collected from Khulna-Satkhira region [...]- 0
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- E. Filho, P. Ávila, C. Bastos, A. Batista, L. Naves, R. Marreto, E. Lima, E. Mendonça, M. ValadaresCollection of Toxicology Reports (2017).
Abstract
Intestinal mucositis is a frequent limiting factor in anticancer therapy and there is currently no broadly effective treatment targeted to cure this side effect. This study aimed to evaluate the effects of a mucoadhesive formulation containing curcuminoids (MFC) from Curcuma longa L. on the pathogenesis of 5-fluorouracil (5-FU)-induced intestinal mucositis. Three intraperitoneal 5-FU injections (200 mg/kg) were used to induce intestinal mucositis in adult Swiss male mice. Treatment was provided orally (MFC 3.75, 7.5 and 15 mg/kg), thirty minutes before 5-FU injections, daily until euthanasia. Duodenal samples were collected to perform morphometric and histopathological analysis, to investigate the expression of Ki-67, p53, Bax and Bcl-2 by immunohistochemistry, to evaluate neutrophil activity myeloperoxidase (MPO)-mediated and oxidative stress by malondialdehyde (MDA) determination. Mice body weight was assessed as well. As expected, 5-FU induced a significant weight loss (∼17%, P < 0.001), shortening in villi height (∼55.4%) and crypts depth (∼47%), and increased (∼64%) the histological severity score when compared to other groups (P < 0.05). These pathological changes were markedly alleviated by the three MFC treatment doses (P < 0.05), in special with the dose MFC 15 mg/kg. This dose also stimulated cell proliferation by ∼90% in the epithelial cells lining from villi and crypts (P < 0.05), reduced MPO levels and MDA formation by 60% and 44%, respectively (P < 0.05). Our data suggest the therapeutic potential of the formulation for treating intestinal mucositis in mice. Supplementary studies are underway searching for the elucidation of mechanisms involved in the protective effects of MFC in order to make this formulation a clinical tool for mucositis treatment.Abstract
Intestinal mucositis is a frequent limiting factor in anticancer therapy and there is currently no broadly effective treatment targeted to cure this side effect. This study [...]- 0
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- M. Cruz, S. Barroso, J. Navoni, M. Teles, J. Barbosa-Filho, H. Rocha, V. AmaralCollection of Toxicology Reports (2017).
Abstract
Hecogenin is a sapogenin found in Agave species in high quantities and is responsible for the many therapeutic effects of these medicinal plants. In addition, this compound is also widely used in the pharmaceutical industry as a precursor for the synthesis of steroidal hormones and anti-inflammatory drugs. Despite Hecogenin being widely used, little is known about its toxicological properties. Therefore, the present study aimed to investigate the cytotoxic, genotoxic and mutagenic effects of Hecogenin on HepG2 cells. Cytotoxicity was analyzed using the MTT test. Then, genotoxic and mutagenic potentials were assessed by comet assay and cytokinesis-block micronucleus assay, respectively. Cytotoxic effect was observed only when cells were exposed to concentrations of Hecogenin equal or higher than 100 μM. Although a lower concentration of Hecogenin caused DNA damage, a reduction on nuclear mutagenic markers in HepG2 cells was observed. The results indicated that Hecogenin treatment generated DNA damage, but in fact it would be repaired, avoiding dissemination of the damage throughout the cell division. Further studies need to be performed to confirm the observed protective effect of Hecogenin against genomic instability.Abstract
Hecogenin is a sapogenin found in Agave species in high quantities and is responsible for the many therapeutic effects of these medicinal plants. In addition, this compound [...]- 0
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- S. Benhamed, F. Guardiola, S. Martínez, M. Martínez-Sánchez, C. Pérez-Sirvent, M. Mars, M. EstebanCollection of Toxicology Reports (2017).
Abstract
Heavy metals incidence in the aquatic environment and its accumulation in fish are under constant review. Gilthead seabream (Sparus aurata ) specimens were exposed for two weeks to sediments highly concentrated in metals, collected at the Portman Bay (Murcia, Spain). The metals bioaccumulation was tested in liver, muscle and skin. The potential of the sediment exposure to induce variation of the stress biomarkers genes was conducted in liver and skin. Results revealed that sediments were highly contaminated with metals. However, following 2 weeks exposure to the sediments, Cd accumulates only in liver. Interestingly, the expression of the genes mta, hsp 70 and hsp 90 were significantly down-regulated in skin. Nevertheless, cyp1a1 gene was up-regulated only in liver. Results uphold that the stress response magnitude was organ-dependent and the skin was the most responsive tissue to metal stress conditions. These results suggest that skin should be considered as target organ for biomarkers analysis in fishes.Abstract
Heavy metals incidence in the aquatic environment and its accumulation in fish are under constant review. Gilthead seabream (Sparus aurata ) specimens were exposed for two [...]- 0
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- S. Yoshie, Y. Ogasawara, M. Ikehata, K. Ishii, Y. Suzuki, K. Wada, K. Wake, S. Nakasono, M. Taki, C. OhkuboCollection of Toxicology Reports (2017).
Abstract
The embryotoxic effect of intermediate frequency (IF) magnetic field (MF) was evaluated using murine embryonic stem (ES) cells and fibroblast cells based on the embryonic stem cell test (EST). The cells were exposed to 21 kHz IF–MF up to magnetic flux density of 3.9 mT during the cell proliferation process (7 days) or the cell differentiation process (10 days) during which an embryonic body differentiated into myocardial cells. As a result, there was no significant difference in the cell proliferation between sham- and IF–MF-exposed cells for both ES and fibroblast cells. Similarly, the ratio of the number of ES-derived cell aggregates differentiated to myocardial cells to total number of cell aggregates was not changed by IF–MF exposure. In addition, the expressions of a cardiomyocytes-specific gene, Myl2, and an early developmental gene, Hba-x, in the exposed cell aggregate were not altered. Since the magnetic flux density adopted in this study is much higher than that generated by an inverter of the electrical railway, an induction heating (IH) cooktop, etc . in our daily lives, these results suggested that IF–MF in which the public is exposed to in general living environment would not have embryotoxic effect.Abstract
The embryotoxic effect of intermediate frequency (IF) magnetic field (MF) was evaluated using murine embryonic stem (ES) cells and fibroblast cells based on the embryonic [...]- 0
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- G. Reddy, F. Antwi, G. Shrestha, T. KuriwadaCollection of Toxicology Reports (2017).
Abstract
The alfalfa weevil, Hypera postica (Coleoptera: Curculionidae), is a major pest of alfalfa Medicago sativa L. (Fabaceae). While H. postica usually causes the most damage before the first cutting, in summer of 2015 damaging levels of the pest persisted in Montana well after the first harvest of alfalfa. Although conventional insecticides can control H. postica, these chemicals have adverse effects on non-target organisms including pollinators and natural enemy insects. In this context, use of biorational insecticides would be the best alternative options, as they are known to pose less risk to non-target organisms. We therefore examined the six commercially available biorational insecticides against H. postica under laboratory condition: Mycotrol® ESO (Beauveria bassiana GHA), Aza-Direct® (Azadirachtin), Met52® EC (Metarhizium brunneum F52), Xpectro OD® (B. bassiana GHA + pyrethrins), Xpulse OD® (B. bassiana GHA + Azadirachtin) and Entrust WP® (spinosad 80%). Concentrations of 0.1, 0.5, 1.0, and 2.0 times the lowest labelled rates were tested for all products. However, in the case of Entrust WP, additional concentrations of 0.001 and 0.01 times the lowest label rate were also assessed. Mortality rates were determined at 1–9 days post treatment. Based on lethal concentrations and relative potencies, this study clearly showed that Entrust was the most effective, causing 100% mortality within 3 days after treatment among all the tested materials. With regard to other biorational, Xpectro was the second most effective insecticide followed by Xpulse, Aza-Direct, Met52, and Mycotrol. Our results strongly suggested that these biorational insecticides could potentially be applied for H. postica control.Abstract
The alfalfa weevil, Hypera postica (Coleoptera: Curculionidae), is a major pest of alfalfa Medicago sativa L. (Fabaceae). While H. postica usually causes the most damage before [...]- 0
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- P. Reckziegel, V. Dias, D. Benvegnú, N. Boufleur, R. Barcelos, H. Segat, C. Pase, C. Santos, É. Flores, M. BürgerCollection of Toxicology Reports (2017).
Abstract
The effect of the antioxidant gallic acid (GA) on Pb toxicity in blood, liver and kidney was investigated in the present study. Rats Wistar received Pb nitrate (50 mg/Kg/day, i.p., 5 days) followed by GA (13.5 mg/Kg, p.o., 3 days) or a chelating agent (EDTA, 55 mg/Kg, i.p.). As result, Pb decreased body weight, hematocrit and blood δ-aminolevulinic acid dehydratase (ALA-D) activity. In addition, high Pb levels were observed in blood and tissues, together with increased (1) lipid peroxidation in erythrocytes, plasma and tissues, (2) protein oxidation in tissues and (3) plasma aspartate transaminase (AST) levels. These changes were accompanied by decreasing in antioxidant defenses, like superoxide dismutase (SOD) activity in tissues and catalase (CAT) activity and reduced glutathione (GSH) in liver. GA was able to reverse Pb-induced decrease in body weight and ALA-D activity, as well as Pb-induced oxidative damages and most antioxidant alterations, however it did not decrease Pb bioaccumulation herein as EDTA did. Furthermore, EDTA did not show antioxidant protection in Pb-treated animals as GA did. In conclusion, GA decreased Pb-induced oxidative damages not by decreasing Pb bioaccumulation, but by improving antioxidant defenses, thus GA may be promising in the treatment of Pb intoxications.Abstract
The effect of the antioxidant gallic acid (GA) on Pb toxicity in blood, liver and kidney was investigated in the present study. Rats Wistar received Pb nitrate (50 mg/Kg/day, [...]- 0
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- R. Kumar, T. BanerjeeCollection of Toxicology Reports (2017).
Abstract
The impact of sublethal toxicity of sodium arsenite on hematological and certain biochemical parameters of the fresh water catfish Clarias batrachus has been analyzed following exposure of sublethal concentration (1 mg/L, 5% of LC50 value) of sodium arsenite for 10, 30, 45, and 60 days. Arsenic bioaccumulation in the blood tissue of the fish increased progressively with increased period of exposure. The values of total erythrocyte count (TECs), total leucocytes count (TLCs), hemoglobin concentration, and packed cell volume (PCV) 1.40 ± 0.03 × 106 /mm3, 174.83 ± 2.74 × 103 /mm3, 5.01 ± 0.26 g/100 ml, 25.00 ± 1.06 were observed respectively at the end of 60 days of exposure. The results of hematological indices were found to be 179.23 ± 8.81fl/cell for mean corpuscular volume (MCV), 35.92 ± 1.89 pg/cell for mean corpuscular hemoglobin (MCH) and 20.17 ± 1.12 g/dl for mean corpuscular hemoglobin concentration (MCHC). The present findings are clearly indicating severe fish anemia due to the arsenic salt exposure. The continued arsenic toxicity results in decreased serum protein concentration that might be a cause for the loss of weight as well as weakness in the fish.Abstract
The impact of sublethal toxicity of sodium arsenite on hematological and certain biochemical parameters of the fresh water catfish Clarias batrachus has been analyzed following [...]- 0
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- Q. Le, K. Tabuchi, A. HaraCollection of Toxicology Reports (2017).
Abstract
Ceramide-1-phosphate (C1P) is a phosphorylated form of ceramide. While ceramide is known to be an inducer of apoptosis of cochlear hair cells in cisplatin ototoxicity, little is known about the function of C1P in cochlear diseases. The present study was designed to examine whether C1P could protect cochlear hair cells against cisplatin ototoxicity. Explants of cochlear basal turns collected from C57BL/6J mice at postnatal days 3–5 were used in all experiments. Cochlear explants were exposed to 5 or 10 μM cisplatin for 48 h to assess the effects of C1P, NVP-231 (a ceramide kinase inhibitor), or ceramide. Western blotting of pAkt/Akt and pMAPK/MAPK was examined to check whether this pathway was modulated by C1P. C1P activated the Akt and MAPK pathway and significantly reduced cochlear cell death induced by cisplatin. Coadministration of cisplatin and ceramide significantly increased cochlear hair cell death. In addition, when treating cochlear hair cells with NVP-231 in the presence of cisplatin or ceramide, a remarkable increase in apoptosis of hair cells was observed. The present findings confirmed the protective effects of C1P in the cisplatin ototoxicity. The balance between ceramide and C1P may play a critical role in the determination of hair cell fate in cisplatin ototoxicity.Abstract
Ceramide-1-phosphate (C1P) is a phosphorylated form of ceramide. While ceramide is known to be an inducer of apoptosis of cochlear hair cells in cisplatin ototoxicity, little [...]- 0
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- B. Qaqish, O. Al-Dalahmah, Y. Al-Motassem, A. Battah, S. IsmailCollection of Toxicology Reports (2017).
Abstract
An increased incidence of non-Hodgkin’s lymphoma (NHL) has been reported in farmers and other occupational groups working with pesticides. In these individuals, an increased prevalence of the chromosomal translocation t(14, 18)(q32, q21), one of the most common chromosomal abnormalities in NHL, has been detected in peripheral blood lymphocytes. This translocation juxtaposes the antiapoptotic BCL2 protein to the immunoglobulin heavy chain gene locus (IGH) leading to overexpression of BCL2. This causes an increase in cell survival, paving the way for malignant transformation. The present study aimed to evaluate the association between the occurrence of the chromosomal translocation t(14, 18) and occupational exposure to pesticides among a group of Jordanian farmers. A total of 192 male subjects including 96 agricultural workers and 96 control subjects participated in this study. BCL2-IGH t(14, 18) fusions were detected by a nested polymerase chain reaction (PCR) assay targeting the major breakpoint region (MBR). We found that occupational exposure to pesticides in open-field farming and insecticide used on animals increased the frequency of the chromosomal translocation t(14, 18). Farmers occupationally exposed to pesticides and insecticide were 13.5 times more likely to harbor t(14, 18). 63.5% (61 of 96) of farmers compared to 11.5% (11 of 96) of controls carried the translocation (odds ratio: 13.5, 95% confidence interval (CI) = 6.3–28.6). We ruled out the influence of possible confounding factors such as age, duration of sun exposure, alcohol intake, smoking, and use of personal protective equipment. Our results indicate that pesticides increased the frequency of chromosomal translocation in the 14q32 region. Accordingly, the presented data agrees with previous suggestions from the literature that pesticides might be involved in the development of NHL through the t(14, 18) pathway.Abstract
An increased incidence of non-Hodgkin’s lymphoma (NHL) has been reported in farmers and other occupational groups working with pesticides. In these individuals, an increased [...]- 0
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- O. Azu, A. Jegede, O. Ugochukwu, I. Onanuga, S. Kharwa, E. NaiduCollection of Toxicology Reports (2017).
Abstract
As the roll-out of antiretroviral therapy continues to drive downwards morbidity and mortality in people living with HIV/AIDS (PLWHAs), organ toxicities (especially the liver) are frequently becoming a major concern for researchers, scientists and healthcare planners. This study was conducted to investigate the possible protective effect of Hypoxis hemerocallidea (AP) against highly active antiretroviral therapy (HAART)-induced hepatotoxicity. A total of 63 pathogen-free adult male Sprague-Dawley rats were divided into 9 groups and treated according to protocols. While no mortality was reported, animals treated with adjuvant HAART and AP recorded least% body weight gain. Significant derangements in serum lipid profiles were exacerbated by treatment of with AP as LDL (increased p < 0.03), triglycerides (increased p < 0.03) with no change in total cholesterol levels. Adjuvant AP with HAART caused reduction in LDL (p < 0.05 and 0.03), increased HDL (p < 0.05) and TG (p < 0.05 and 0.001 for AP100 and AP200 doses respectively). Markers of liver injury assayed showed significant increase (p < 0.003, 0.001) in AST in AP alone as well as HAART+ vitamins C and E groups respectively. Adjuvant HAART and AP and vitamins C and E also caused significant declines in ALT and ALP levels. Serum GGT was not markedly altered. Disturbances in histopathology ranged from severe hepatocellular distortions, necrosis and massive fibrosis following co-treatment of HAART with vitamins C and E as well as HAART alone. These results warrant caution on the adjuvant use of AP with HAART by PLWHAs as implications for hepatocellular injuries are suspect with untoward cardiometabolic changes.Abstract
As the roll-out of antiretroviral therapy continues to drive downwards morbidity and mortality in people living with HIV/AIDS (PLWHAs), organ toxicities (especially the liver) [...]- 0
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- E. Nwaichi, S. NtorgboCollection of Toxicology Reports (2017).
Abstract
Levels of sixteen polycyclic aromatic hydrocarbons (PAHs) in 30 edible tissues of selected frequently-consumed fish and seafood collected from three coastal waters of Niger Delta, namely, Sime, Kporghor and Iko were investigated in 2014. Gas chromatographic analysis were employed for PAHs determination. Observed mean PAHs levels in the samples ranged from below detection limit (BD) of analytical instrument to 22.400 ± 0.050 μg kg−1 wet wt. in Littorina littorea, BD to 87.400 ± 0.030 μg kg−1 wet wt. in Crassostrea virginica and from BD to 171.000 ± 0.430 μg kg−1 wet wt. in Periophthalmus koeleuteri. The highest average concentration of 171.000 ± 0.430 μg kg−1 wet wt. was recorded for Indeno [1, 2, 3-cd]pyrene from Sime water. High molecular weight PAHs (HMW-PAHs) were generally predominant compared to low molecular weight PAHs (LMW-PAHs). The LMW- PAH/HMW-PAH ratio wasAbstract
Levels of sixteen polycyclic aromatic hydrocarbons (PAHs) in 30 edible tissues of selected frequently-consumed fish and seafood collected from three coastal waters of Niger [...]- 0
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- D. Mwalwayo, B. TholeCollection of Toxicology Reports (2017).
Abstract
A study was carried out to assess levels of contamination of aflatoxins and fumonisins (B1 + B2 ) in maize produced, stored and consumed in rural households in Malawi. A total of 9 districts were selected across the country representing 3 districts from each of the Northern, Central and Southern regions respectively. Households were selected at random in each district where 10 maize samples were collected for laboratory analysis. Aflatoxins and fumonisins were analyzed using a single step lateral flow immunochromatographic assay based on a competitive immunoassay format. The detection limit for aflatoxins was 2 μg/kg with a quantitation range of 2–150 μg/kg and that for fumonisins was 1 mg/kg with a quantitation range of 1–7 mg/kg. It was found that samples in the Southern region were highly contaminated, with the Chikhwawa district having high levels of both aflatoxins and fumonisins in maize. The Northern region had the least contamination. The maximum detected amount of aflatoxins was 140 μg/kg. The maximum detected amounts of fumonisins was 7 mg/kg. About 20% of maize samples exceeded the tolerable maximum limit for aflatoxins in Malawi. Aflatoxins and fumonisins were found to co-occur with contamination levels exceeding 100 μg/kg for both aflatoxins and fumonisins.Abstract
A study was carried out to assess levels of contamination of aflatoxins and fumonisins (B1 + B2 ) in maize produced, stored and consumed in rural households in Malawi. A total [...]- 0
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- M. Mossoba, T. Flynn, S. Vohra, P. Wiesenfeld, R. SprandoCollection of Toxicology Reports (2017).
Abstract
Adhatoda zeylanica is a dietary supplement ingredient present in several types of dietary supplements, including weight loss, respiratory relief, and immune regulating products. Due to its reported wide range of uses in folk medicine, it was hypothesized that it may have the potential to target multiple organs and lead to a range of toxicity features. As a preliminary evaluation of the safety of this herbal ingredient, an investigation into its effects on the kidney was sought. An in vitro study of its potential nephrotoxicity using the HK-2 human proximal tubule cell line in a variety of functional indicators was performed to capture both general forms of cellular toxicity as well as ones that are specific to proximal tubules. A. zeylanica was only capable of inducing detrimental short-term toxicity to HK-2 cells at relatively high treatment concentrations when exposed directly to the cells. The lack of acute and potent toxicity of A. zeylanica under our experimental conditions calls for further studies to better define its toxicant threshold and establish safe dosage levels.Abstract
Adhatoda zeylanica is a dietary supplement ingredient present in several types of dietary supplements, including weight loss, respiratory relief, and immune regulating products. [...]- 0
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- R. Matulka, T. Chan, R. Green, J. Carney, S. Franklin, P. LicariCollection of Toxicology Reports (2017).
Abstract
Microalgae are increasingly being utilized as food ingredients for a variety of applications, including as sources of protein, egg and dairy substitutes, and cooking oils. The dietary safety of a new structuring fat produced using a heterotrophic fermentation process by a strain of Prototheca moriformis was evaluated in a 13-week dietary toxicity study and compared with kokum fat, a structuring fat of similar composition used in the food industry and derived from Garcinia indica seeds. The algal structuring fat was evaluated for its genotoxic potential using both in vitro and in vivo assays. No treatment-related adverse events occurred in rats consuming algal structuring fat or kokum fat in the 13-week study, no treatment-related effects were reported for body weight, food consumption, urinalysis, hematology, clinical chemistry, gross pathology, organ weights, or histopathology. While statistically significant effects occurred in some parameters, none were dose-related or considered adverse. Overall, the NOAELs for the algal structuring fat and the kokum fat were 100 000 ppm, the highest concentrations tested. The algal structuring fat was not mutagenic in the bacterial reverse mutation assay in the Salmonella typhimurium or Escherichia coli strains tested and was not clastogenic in the in vivo mouse bone marrow chromosome aberration assay.Abstract
Microalgae are increasingly being utilized as food ingredients for a variety of applications, including as sources of protein, egg and dairy substitutes, and cooking oils. [...]- 0
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- R. Maronpot, C. Hobbs, J. Davis, C. Swartz, M. Boyle, M. Koyanagi, S. HayashiCollection of Toxicology Reports (2017).
Abstract
Microbiologically derived cyclodextrin glucanotransferase (CGTase) is used commercially as a processing agent in manufacture of food, pharmaceuticals, and cosmetics. Its toxic potential was evaluated in anticipation of use in the production of alpha -glycosyl isoquercitrin, a water-soluble form of quercetin. Following OECD guidelines, CGTase, produced by Bacillus pseudalcaliphilus DK-1139, was evaluated in a genotoxicity battery consisting of a bacterial reverse mutation assay, an in vitro micronucleus (MN) assay and MN and comet assays using B6C3F1 male and female mice. These same genotoxicity assays were also conducted for sodium sulfate, a contaminant of CGTase preparation. In a 90-day Sprague Dawley rat toxicity study, CGTase was administered by gavage in water at daily doses of 0, 250, 500, and 1000 mg/kg/day. CGTase did not induce mutations with or without metabolic activation in the bacterial reverse mutation assay. Formation of micronuclei was not induced in either in vitro or in vivo MN assays with or without metabolic activation. No induction of DNA damage was detected in male or female mouse liver, stomach, or duodenum in the comet assay. Sodium sulfate also tested negative in these same genotoxicity assays. In the 90-day repeated dose rat study there were no treatment-related adverse clinical or pathological findings. The genotoxicity assays and repeated dose toxicity study support the safe use of CGTase in production of alpha -glycosyl isoquercitrin.Abstract
Microbiologically derived cyclodextrin glucanotransferase (CGTase) is used commercially as a processing agent in manufacture of food, pharmaceuticals, and cosmetics. Its toxic [...]- 0
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- L. Vijayasteltar, G. Nair, B. Maliakel, R. Kuttan, K. I.M.Collection of Toxicology Reports (2017).
Abstract
Despite the various reports on the toxicity of clove oil and its major component eugenol, systematic evaluations on the safety of polyphenolic extracts of clove buds have not been reported. Considering the health beneficial pharmacological effects and recent use of clove polyphenols as dietary supplements, the present study investigated the safety of a standardized polyphenolic extract of clove buds (Clovinol), as assessed by oral acute (5 g/kg b.wt. for 14 days) and subchronic (0.25, 0.5 and 1 g/kg b.wt. for 90 days) toxicity studies on Wistar rats and mutagenicity studies employing Salmonella typhimurium strains. Administration of Clovinol did not result in any toxicologically significant changes in clinical/behavioural observations, ophthalmic examinations, body weights, organ weights, feed consumption, urinalysis, hematology and clinical biochemistry parameters when compared to the untreated control group of animals, indicating the no observed-adverse-effect level (NOAEL) as 1000 mg/kg b.wt./day, the highest dose tested. Terminal necropsy did not reveal any treatment-related histopathology changes. Clovinol did not show genotoxicity when tested on TA-98, TA-100 and TA-102 with or without metabolic activation, rather exhibited significant antimutagenic potential against the known mutagens, sodium azide, NPD and tobacco as well as against 2-acetamidoflourene, which needed metabolic activation for mutagenicity.Abstract
Despite the various reports on the toxicity of clove oil and its major component eugenol, systematic evaluations on the safety of polyphenolic extracts of clove buds have [...]- 0
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- S. Lelli, M. Mazzetti, L. VialeCollection of Toxicology Reports (2017).
Abstract
This work investigated the modulation by melatonin (Mel) of the effects of the porphyrinogenic drugs 2-allyl-2-isopropylacetamide (AIA) and 3, 5-diethoxycarbonyl-1, 4-dihydro-2, 4, 6-collidine (DDC) on oxidative environment, glucose biosynthesis and heme pathway parameters. Administration of Mel before rat intoxication with AIA/DDC showed a clear beneficial effect in all cases. Mel induced decreases of 42% and 35% in the excretion of the hemeprecursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), respectively, and a 33% decrease in the induction of the heme regulatory enzyme 5-aminolevulinic acid-synthase (ALA-S). The activity of the glucose metabolism enzyme phosphoenolpyruvate carboxykinase (PEPCK), which had been diminished by the porphyrinogenic treatment, was restored by 45% when animals were pre-treated with Mel. Mel abolished the modest decrease in glucose 6-phospatase (G6Pase) activity caused by AIA/DDC treatment. The oxidative status of lipids was attenuated by Mel treatment in homogenates by 47%, whereas no statistically significant AIA/DDC-induced increase in thiobarbituric acid reactive substances (TBARS) was observed in microsomes after Mel pre-treatment. We hypothesize that Mel may be scavenging reactive species of oxygen (ROS) that could be damaging lipids, PEPCK, G6Pase and ferrochelatase (FQ). Additionally, Mel administration resulted in the repression of the key enzyme ALA-S, and this could be due to an increase in glucose levels, which is known to inhibit ALA-S induction. The consequent decrease in levels of the heme precursors ALA and PBG had a beneficial effect on the drug-induced porphyria. The results obtained open the possibility of further research on the use of melatonin as a co-treatment option in acute porphyria.Abstract
This work investigated the modulation by melatonin (Mel) of the effects of the porphyrinogenic drugs 2-allyl-2-isopropylacetamide (AIA) and 3, 5-diethoxycarbonyl-1, 4-dihydro-2, [...]- 0
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- L. Takser, N. Benachour, B. Husk, H. Cabana, D. GrisCollection of Toxicology Reports (2017).
Abstract
Cyanotoxins have been shown to be highly toxic for mammalian cells, including brain cells. However, little is known about their effect on inflammatory pathways. This study investigated whether mammalian brain and immune cells can be a target of certain cyanotoxins, at doses approximating those in the guideline levels for drinking water, either alone or in mixtures. We examined the effects on cellular viability, apoptosis and inflammation signalling of several toxins on murine macrophage-like RAW264.7, microglial BV-2 and neuroblastoma N2a cell lines. We tested cylindrospermopsin (CYN), microcystin-LR (MC-LR), and anatoxin-a (ATX-a), individually as well as their mixture. In addition, we studied the neurotoxins β-N -methylamino-l -alanine (BMAA) and its isomer 2, 4-diaminobutyric acid (DAB), as well as the mixture of both. Cellular viability was determined by the MTT assay. Apoptosis induction was assessed by measuring the activation of caspases 3/7. Cell death and inflammation are the hallmarks of neurodegenerative diseases. Thus, our final step was to quantify the expression of a major proinflammatory cytokine TNF-α by ELISA. Our results show that CYN, MC-LR and ATX-a, but not BMAA and DAB, at low doses, especially when present in a mixture at threefold less concentrations than individual compounds are 3–15 times more potent at inducing apoptosis and inflammation. Our results suggest that common cyanotoxins at low doses have a potential to induce inflammation and apoptosis in immune and brain cells. Further research of the neuroinflammatory effects of these compounds in vivo is needed to improve safety limit levels for cyanotoxins in drinking water and food.Abstract
Cyanotoxins have been shown to be highly toxic for mammalian cells, including brain cells. However, little is known about their effect on inflammatory pathways. This study [...]- 0
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- K. Lien, D. Hsieh, H. Huang, C. Wu, S. Ni, M. LingCollection of Toxicology Reports (2017).
Abstract
The purpose of this study was to assess the health risk associated with dietary intake of sulfites for Taiwanese general consumers by conducting a total diet study (TDS). We evaluated the exposure of Taiwanese to sulfites in the diet and its associated health risk. This study used a list of 128 food items representing 83% of the total daily diet. Among the 128 food items, 59 items may contain sulfites. Samples of the 59 food items were collected and subjected to chemical analysis to determine the sulfur dioxide concentration. Health risk was assessed by calculating the ratio of exposure level to the acceptable daily intake (ADI) level of the analyte. For high-intake consumers, the HI of sulfites was 19.7% ADI for males over the age of three years at the 95th percentile, whereas for females over the age of 66, the HI was 17.8% ADI. The HI for high-intake consumers was above 10% ADI. This suggests that regulatory actions must be continued and that consumers should be advised to be aware of processed foods with relatively high contamination to avoid excessive exposure.Abstract
The purpose of this study was to assess the health risk associated with dietary intake of sulfites for Taiwanese general consumers by conducting a total diet study (TDS). [...]- 0
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- D. JonesCollection of Toxicology Reports (2017).
Abstract
The exposome is a complement to the genome that includes non-genetic causes of disease. Multiple definitions are available, with salient points being global inclusion of exposures and behaviors, and cumulative integration of associated biologic responses. As such, the concept is both refreshingly simple and dauntingly complex. This article reviews high-resolution metabolomics (HRM) as an affordable approach to routinely analyze samples for a broad spectrum of environmental chemicals and biologic responses. HRM has been successfully used in multiple exposome research paradigms and is suitable to implement in a prototype universal exposure surveillance system. Development of such a structure for systematic monitoring of environmental exposures is an important step toward sequencing the exposome because it builds upon successes of exposure science, naturally connects external exposure to body burden and partitions the exposome into workable components. Practical results would be repositories of quantitative data on chemicals according to geography and biology. This would support new opportunities for environmental health analysis and predictive modeling. Complementary approaches to hasten development of exposome theory and associated biologic response networks could include experimental studies with model systems, analysis of archival samples from longitudinal studies with outcome data and study of relatively short-lived animals, such as household pets (dogs and cats) and non-human primates (common marmoset). International investment and cooperation to sequence the human exposome will advance scientific knowledge and also provide an important foundation to control adverse environmental exposures to sustain healthy living spaces and improve prediction and management of disease.Abstract
The exposome is a complement to the genome that includes non-genetic causes of disease. Multiple definitions are available, with salient points being global inclusion of exposures [...]- 0
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- J. Bai, P. Lei, C. Zhao, Y. Wang, D. Yan, S. YangCollection of Toxicology Reports (2017).
Abstract
This study investigated the effects of Na2 SO3 on the fat metabolism in human normal diploid HL-7702 (referred as L-02) hepatocytes. After 24 h and 48 h, treatment with different concentrations of Na2 SO3, the intra and extra-hepatocellular triglyceride (TG) contents of L-02 were determined using chemical-enzymatic method. The contents of very low-density lipoprotein (VLDL) and apolipoprotein B100 (apoB100) in the culture supernatants were determined using enzyme-linked immunosorbent assay (ELISA). Western blot was applied to detect the expressions of fatty acid oxidation and fat synthesis related proteins, VLDL assembly and secretion in L-02 cells. Na2 SO3 treatment (10 mM, 24 h/48 h) significantly increased the intra TG level in the hepatocytes. Different concentrations of Na2 SO3 increased the extra-hepatocellular TG content. After 24 h exposure, the extracellular VLDL levels and secretions of apoB100 in 0.1–10 mM Na2 SO3 groups were significantly higher than that of the negative control (P < 0.05). Meanwhile, the expression of CPT1 and SREBP1 protein were significantly reduced by Na2 SO3 . MTP and TGH protein expressions were significantly elevated in each Na2 SO3 treatment group. The expression level of LDLR in hepatocytes was reduced by Na2 SO3 . Na2 SO3 exposure may promote the hepatocellular VLDL assembly and secretion, through increasing of MTP and TGH expressions and inhibiting the uptake of extracelluar VLDL.Abstract
This study investigated the effects of Na2 SO3 on the fat metabolism in human normal diploid HL-7702 (referred as L-02) hepatocytes. After 24 h and 48 h, treatment with different [...]- 0
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- L. Felix, J. Perez, M. Contreras, T. Ravasi, J. KoselCollection of Toxicology Reports (2017).
Abstract
The increasing interest in the use of magnetic nanostructures for biomedical applications necessitates rigorous studies to be carried out in order to determine their potential toxicity. This work attempts to elucidate the cytotoxic effects of nickel nanowires (NWs) in human fibroblasts WI-38 by a colorimetric assay (MTT) under two different parameters: NW concentration and exposure time. This was complemented with TEM and confocal images to assess the NWs internalization and to identify any changes in the cell morphology. Ni NWs were fabricated by electrodeposition using porous alumina templates. Energy dispersive X-ray analysis, scanning electron microscopy and transmission electron microscopy imaging were used for NW characterization. The results showed decreased cell metabolic activity for incubation times longer than 24 h and no negative effects for exposure times shorter than that. The cytotoxicity effects for human fibroblasts were then compared with those reported for HCT 116 cells, and the findings point out that it is relevant to consider the cellular size. In addition, the present study compares the toxic effects of equivalent amounts of nickel in the form of its salt to those of NWs and shows that the NWs are more toxic than the salts. Internalized NWs were found in vesicles inside of the cells where their presence induced inflammation of the endoplasmic reticulum.Abstract
The increasing interest in the use of magnetic nanostructures for biomedical applications necessitates rigorous studies to be carried out in order to determine their potential [...]- 0
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- S. Borghoff, D. Wikoff, S. Harvey, L. HawsCollection of Toxicology Reports (2017).
Abstract
Tetrabromobisphenol A (TBBPA), a nongenotoxic flame retardant, causes uterine tumors in female rats. A proposed mode of action (MoA) for these tumors involves an increase in the bioavailability of estradiol as a result of TBBPA inhibiting estrogen sulfotransferases (ES), the enzymes responsible for inactivating and enhancing the elimination of estradiol. The objective of this study was to evaluate the effect of dose and repeated administration of TBBPA on the level of TBBPA, TBBPA-glucuronide (GA) and TBBPA-sulfate (S) conjugates in plasma, liver and uterus of female Wistar Han rats administered TBBPA (50, 100, 250, 500 or 1000 mg/kg) for 28 consecutive days. In accordance with this objective, TBBPA sulfation was used as a surrogate for evaluating the potential for estradiol sulfation to be limited at high dose levels of TBBPA. Blood samples were collected at 4 and 8 h post-dosing on study day 7, 14, and 28, while liver and uterus were collected at the same time points following 28 days of dosing. Tissue samples were analyzed for TBBPA, TBBPA-GA and TBBPA-S by LC–MS/MS. A dose-related increase in the concentration of all three analytes occurred in plasma (day 7, 14, and 28) as well as liver and uterus tissue (day 28) at both 4 and 8 h post dose. The plasma concentration of TBBPA-GA and TBBPA-S was higher in animals dosed for 28 days compared to those dosed for 7 or 14 days showing an increase in systemic circulation of these conjugates with repeated administration. The balance of these conjugates was also different in tissues with TBBPA-S > TBBPA-GA at high doses in the liver and TBBPA-GA > TBBPA-S in both plasma and uterus. In all three tissues the ratio of TBBPA-S/TBBPA-GA showed a decreasing trend with dose, suggesting that at high TBBPA dose levels sulfation of TBBPA becomes limited. This effect was most apparent in the liver and plasma at 28 days of administration. Together these data show that administration of high doses of TBBPA associated with the induction of uterine tumors, results in a disruption in the balance of conjugates reflected by a decrease in the TBBPA-S/TBBPA-GA ratio. A limitation in the sulfation of TBBPA in vivo supports in vitro data defining TBBPA as an inhibitor of ES activity, thus providing further support that the proposed MoA occurs under conditions of high dose, chronic TBBPA administration to Wistar Han rats. Given that the uterine tumors observed in rats (250–1000 mg/kg-day) only occur at very high doses that perturb homeostatic control, it is unlikely such effects would occur in humans given that current TBBPA exposure levels are approximately eight orders of magnitude lower than these doses that are associated with exceeding the capacity of conjugation pathways in animal studies.Abstract
Tetrabromobisphenol A (TBBPA), a nongenotoxic flame retardant, causes uterine tumors in female rats. A proposed mode of action (MoA) for these tumors involves an increase [...]- 0
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The possible role of intravenous lipid emulsion in the treatment of chemical warfare agent poisoning
A. Eisenkraft, A. FalkCollection of Toxicology Reports (2017).
Abstract
Organophosphates (OPs) are cholinesterase inhibitors that lead to a characteristic toxidrome of hypersecretion, miosis, dyspnea, respiratory insufficiency, convulsions and, without proper and early antidotal treatment, death. Most of these compounds are highly lipophilic. Sulfur mustard is a toxic lipophilic alkylating agent, exerting its damage through alkylation of cellular macromolecules (e.g., DNA, proteins) and intense activation of pro-inflammatory pathways. Currently approved antidotes against OPs include the peripheral anticholinergic drug atropine and an oxime that reactivates the inhibited cholinesterase. Benzodiazepines are used to stop organophosphate-induced seizures. Despite these approved drugs, efforts have been made to introduce other medical countermeasures in order to attenuate both the short-term and long-term clinical effects following exposure. Currently, there is no antidote against sulfur mustard poisoning. Intravenous lipid emulsions are used as a source of calories in parenteral nutrition. In recent years, efficacy of lipid emulsions has been shown in the treatment of poisoning by fat-soluble compounds in animal models as well as clinically in humans. In this review we discuss the usefulness of intravenous lipid emulsions as an adjunct to the in-hospital treatment of chemical warfare agent poisoning.Abstract
Organophosphates (OPs) are cholinesterase inhibitors that lead to a characteristic toxidrome of hypersecretion, miosis, dyspnea, respiratory insufficiency, convulsions and, [...]- 0
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- A. Atilano-Roque, X. Wen, L. Aleksunes, M. JoyCollection of Toxicology Reports (2017).
Abstract
Cisplatin is a chemotherapeutic agent used in the treatment of solid tumors, with clinical use often complicated by kidney toxicity. Nuclear factor (erythroid-derived-2)-like 2 (Nrf2) is a transcription factor involved in kidney protectant effects. The purpose of this study was to determine whether the Nrf2 activators oltipraz, sulforaphane, and oleanolic acid could protect human kidney cells against cisplatin-induced injury and to compare the protective effects between three Nrf2 activators. Human proximal tubule cells (hPTC) and human embryonic kidney 293 cells (HEK293) were exposed to cisplatin doses in the absence and presence of Nrf2 activators. Pre- and delayed-cisplatin and Nrf2 activator exposures were also assessed. Cell viability was enhanced with Nrf2 activator exposures, with differences detected between pre- and delayed-treatments. Both sulforaphane and oltipraz increased the expression of anti-oxidant genes GCLC and NQO1. These findings suggest potential human kidney protective benefits of Nrf2 activators with planned exposures to cisplatin.Abstract
Cisplatin is a chemotherapeutic agent used in the treatment of solid tumors, with clinical use often complicated by kidney toxicity. Nuclear factor (erythroid-derived-2)-like [...]- 0
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- A. Asmari, H. Shahrani, N. Masri, A. Faraidi, I. Elfaki, M. ArshaduddinCollection of Toxicology Reports (2017).
Abstract
Vanillin is commonly used as an additive in food, medicine and cosmetics, but its effect has not yet been studied in gastric injury. Therefore the effect of vanillin was studied in experimental gastric ulcer. Gastric secretion and acidity were studied in pylorus ligated rats. Ulcer index, levels of gastric mucus, malondialdehyde (MDA), myeloperoxidase activity (MPO), expression of nuclear factor kappa B (NF-κB) p65, and histopathological changes were determined in ethanol induced gastric ulcer. Pre treatment with vanillin significantly reduced gastric secretion (P < 0.001) and acidity (P < 0.0001) and gastric ulcer index scores (P < 0.001). and augmented the gastric mucosal defense. Vanillin significantly restored the depleted gastric wall mucus levels (P < 0.0001) induced by ethanol and also significantly attenuated ethanol induced inflammation and oxidative stress by the suppression of gastric MPO activity (P < 0.001), reducing the expression of NF-κB p65 and the increased MDA levels (P < 0.001). Vanillin was also effective in alleviating the damage to the histological architecture and the activation of mast cells induced by ethanol. Together the results of this study highlight the gastroprotective activity of vanillin in gastric ulcers of rats through multiple actions that include inhibition of gastric secretion and acidity, reduction of inflammation and oxidative stress, suppression of expression of NF-κB, and restoration of the histological architecture.Abstract
Vanillin is commonly used as an additive in food, medicine and cosmetics, but its effect has not yet been studied in gastric injury. Therefore the effect of vanillin was studied [...]- 0
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