Hepatoprotective role of captopril on paraquat induced hepatotoxicity.
Paraquat (PQ) is a highly toxic herbicide that is used in most of the countries without restriction. The cytotoxic effect of PQ is mediated by radicals, which are the products of PQ reduction in cells. The anti-oxidative action of captopril, an angiotensin-converting enzyme inhibitor, appears to be through its ability to scavenge reactive oxygen species. In this study, the heptoprotective effect of captopril against PQ-induced hepatotoxicity was evaluated using primary cultured rat hepatocytes. Hepatocytes were isolated from male Wistar rats using a two-step collagenase perfusion, following incubation in the presence of captopril at 0.1, 0.2, 0.4 and 0.8 mM with or without PQ (5 mM). Hepatoprotective effects of captopril were studied indicating glutathione level intensity, thiobarbituric acid reactive substances (TBARs) formation, lactate dehydrogenase (LDH) leakage and cell viability every 70 min for 210 min. Captopril at 0.2 mM concentration maintained the LDH leakage, glutathione level and cell viability in the presence of 5 mM PQ. In spite of a significant elevation in TBARs formation in the PQ group, captopril did not show any significant protection. In conclusion, our data reveals that incubation of freshly isolated rat hepa-tocytes with captopril (0.2 mM) significantly protected the hepatocytes against the cytotoxicity of PQ (P < 0.05).
Elmi
A
A
Department of Pharmacology, School of Medicine, Medical Sciences/ University of Tehran, Tehran, Iran.
Sadeghi
Zh
Zh
Elmi
S
S
Daraei
B
B
Ghazi-Khansari
M
M
D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D019610:Cytoprotection; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D010269:Paraquat / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D017392:Thiobarbituric Acid Reactive Substances; D002216:Captopril; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D010269:Paraquat