Antioxidant and antimutagenic effect of quercetin against DEN induced hepatotoxicity in rat.
Diethylnitrosamine (DEN), a potent hepatocarcinogen, is found in tobacco smoke, processed meat as well as in different food products. Quercetin (QC), a naturally occurring flavonoid has excellent antioxidant properties. The present study was aimed to investigate the chemoprotective potential of QC against DEN induced hepatotoxicity in Sprague-Dawley (SD) rats. Quercetin was administered (10, 30 and 100 mg/kg) for 5 consecutive days after DEN (200 mg/kg) treatment. The animals were killed 24 h after the last dose of QC/saline treatment. The DEN induced hepatotoxicity was evident by elevated malondialdehyde (MDA) and decreased glutathione (GSH) levels in the liver. A significant increase in the levels of plasma aspartate transaminase (AST) and plasma alanine transaminase (ALT) was observed in the DEN treated group. The DEN induced DNA damage was evaluated using a single cell gel electrophoresis (SCGE) assay. A significant increase in the number of TUNEL positive cells was observed in the DEN treated group. Quercetin restored AST, ALT and GSH levels at all the tested doses. Restoration of the MDA level and cellular morphology was observed at doses of 10 and 30 mg/kg of QC. Further, DEN induced DNA damage and apoptosis was ameliorated by QC. The results indicate that QC ameliorates the DEN induced hepatotoxicity in rats and can be a candidate for a good chemoprotectant.
Gupta
C
C
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Mohali, Punjab-160 062, India.
Vikram
A
A
Tripathi
D N
DN
Ramarao
P
P
Jena
G B
GB
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D020552:Comet Assay; D004249:DNA Damage; D004052:Diethylnitrosamine / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016587:Antimutagenic Agents; D000975:Antioxidants; D004052:Diethylnitrosamine; D008315:Malondialdehyde; D011794:Quercetin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione