Title: | Silymarin prevents benzo(a)pyrene-induced toxicity in Wistar rats by modulating xenobiotic-metabolizing enzymes |
Author(s): | Kiruthiga PV; Karthikeyan K; Archunan G; Pandian SK; Devi KP; |
Address: | "Department of Biotechnology, Alagappa University, Karaikudi, Tamil Nadu, India. Centre for Pheromone Technology, Department of Animal Science, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India. Department of Biotechnology, Alagappa University, Karaikudi, Tamil Nadu, India devikasi@yahoo.com" |
ISSN/ISBN: | 1477-0393 (Electronic) 0748-2337 (Linking) |
Abstract: | "Benzo(a)pyrene (B(a)P), which is commonly used as an indicator species for polycyclic aromatic hydrocarbon (PAH) contamination, has a large number of hazardous consequences on human health. In the presence of the enzyme cytochrome-P-450 1A1 (CYP1A1), it undergoes metabolic activation to form reactive intermediates that are capable of inducing mutagenic, cytotoxic, teratogenic and carcinogenic effects in various species and tissues. Research within the last few years has shown that flavonoids exhibit chemopreventive effect against these toxins. In the present study, the protective effect of silymarin (a flavonoid) against B(a)P-induced toxicity was monitored in Wistar rats by evaluating the levels of hepatic phase I (CYP1A1), phase II enzymes (glutathione-S-transferase, epoxide hydroxylases, uridinediphosphate glucuronosyltransferases, NAD(P)H: quinone oxidoreductase 1, sulfotransferases), cellular antioxidant enzyme heme oxygenase and total glutathione. The results reveal that silymarin possesses substantial protective effect against B(a)P-induced damages by inhibiting phase I detoxification enzyme CYP1A1 and modulating phase II conjugating enzymes, which were confirmed by histopathological analysis. Overall, the inhibition of CYP1A1 and the modulation of phase II enzymes may provide, in part, the molecular basis for the effect of silymarin against B(a)P" |
Keywords: | "Animals Benzo(a)pyrene/*toxicity Chemical and Drug Induced Liver Injury/*enzymology/*prevention & control Cytochrome P-450 CYP1A1/metabolism Dose-Response Relationship, Drug Enzyme Activation Enzyme Repression Female Liver/pathology Protective Agents/*pha;" |
Notes: | "MedlineKiruthiga, P V Karthikeyan, K Archunan, G Pandian, S Karutha Devi, K Pandima eng Research Support, Non-U.S. Gov't England 2013/02/15 Toxicol Ind Health. 2015 Jun; 31(6):523-41. doi: 10.1177/0748233713475524. Epub 2013 Feb 13" |