Resveratrol modulates pyrogallol-induced changes in hepatic toxicity markers, xenobiotic metabolizing enzymes and oxidative stress.
Previously, we reported that pyrogallol, an anti-psoriatic agent, causes hepatotoxicity in experimental animals and silymarin, an herbal antioxidant, reduces pyrogallol-induced changes [Upadhyay, G., Kumar, A., Singh, M.P., 2007. Effect of silymarin on pyrogallol- and rifampicin-induced hepatotoxicity in mouse. Eur. J. Pharmacol. 565, 190-201.]. The present study was undertaken to assess the effect of resveratrol against pyrogallol-induced changes in hepatic damage markers, xenobiotic metabolizing enzymes and oxidative stress. Swiss albino mice were treated intraperitoneally, daily with pyrogallol (40 mg/kg), for one to four weeks, along with respective controls. In some set of experiments, animals were pre-treated with resveratrol (10 mg/kg), 2 h prior to pyrogallol treatment, along with respective controls. Alanine aminotransaminase, aspartate aminotransaminase and bilirubin were measured in blood plasma and mRNA expression of cytochrome P-450 (CYP) 1A1, CYP1A2, CYP2E1, glutathione-S-transferase (GST)-ya and GST-yc, catalytic activity of CYP1A1, CYP1A2, CYP2E1, GST, glutathione reductase and glutathione peroxidase, lipid peroxidation and reduced glutathione (GSH) level were measured in liver. Resveratrol reduced pyrogallol-mediated increase in alanine aminotransaminase, aspartate aminotransaminase, bilirubin, lipid peroxidation and mRNA expression and catalytic activity of CYP2E1 and CYP1A2. Pyrogallol-mediated decrease in GST-ya and GST-yc expressions, GST, glutathione peroxidase and glutathione reductase activities and GSH content was significantly attenuated in resveratrol co-treated animals. CYP1A1 expression and catalytic activity were not altered significantly in any treated groups. The results demonstrate that resveratrol modulates pyrogallol-induced changes in hepatic toxicity markers, xenobiotic metabolizing enzymes and oxidative stress.
Upadhyay
Ghanshyam
G
Indian Institute of Toxicology Research (IITR), Lucknow, India.
Singh
Anand Kumar
AK
Kumar
Abhai
A
Prakash
Om
O
Singh
Mahendra Pratap
MP
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D002384:Catalysis; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000378:metabolism*; D003879:Dermatologic Agents / Q000009:adverse effects*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D011748:Pyrogallol / Q000009:adverse effects*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D000637:Transaminases / Q000097:blood; D015262:Xenobiotics / Q000378:metabolism*
D000975:Antioxidants; D015415:Biomarkers; D003879:Dermatologic Agents; D013267:Stilbenes; D015262:Xenobiotics; D011748:Pyrogallol; D005979:Glutathione Peroxidase; D001189:Aryl Hydrocarbon Hydroxylases; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D000637:Transaminases; D005978:Glutathione; D000077185:Resveratrol; D001663:Bilirubin