Documents published in Scipedia

• Ceramide-1-phosphate protection of cochlear hair cells against cisplatin ototoxicity

  Q. Le, K. Tabuchi, A. Hara

  Collection 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
  •  read

• Occupational exposure to pesticides and occurrence of the chromosomal translocation t(14;18) among farmers in Jordan

  B. Qaqish, O. Al-Dalahmah, Y. Al-Motassem, A. Battah, S. Ismail

  Collection 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
  •  read

• Hepatic histomorphological and biochemical changes following highly active antiretroviral therapy in an experimental animal model: Does Hypoxis hemerocallidea exacerbate hepatic injury?

  O. Azu, A. Jegede, O. Ugochukwu, I. Onanuga, S. Kharwa, E. Naidu

  Collection 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
  •  read

• Assessment of PAHs levels in some fish and seafood from different coastal waters in the Niger Delta

  E. Nwaichi, S. Ntorgbo

  Collection 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 was

  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 [...]

  • 0
  •  read

• Prevalence of aflatoxin and fumonisins (B1  + B2 ) in maize consumed in rural Malawi

  D. Mwalwayo, B. Thole

  Collection 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
  •  read

• In vitro exposure of Adhatoda zeylanica to human renal cells lacks acute toxicity

  M. Mossoba, T. Flynn, S. Vohra, P. Wiesenfeld, R. Sprando

  Collection 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
  •  read

• 13-week dietary study and in vitro and in vivo genotoxicity studies of a structuring fat produced through a microalgal fermentation process

  R. Matulka, T. Chan, R. Green, J. Carney, S. Franklin, P. Licari

  Collection 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
  •  read

• Genetic and rat toxicity studies of cyclodextrin glucanotransferase

  R. Maronpot, C. Hobbs, J. Davis, C. Swartz, M. Boyle, M. Koyanagi, S. Hayashi

  Collection 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
  •  read

• Safety assessment of a standardized polyphenolic extract of clove buds: Subchronic toxicity and mutagenicity studies

  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
  •  read

• Melatonin modulates drug-induced acute porphyria

  S. Lelli, M. Mazzetti, L. Viale

  Collection 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
  •  read