[Effect of captopril on glutathione level in the liver and paracetamol-induced liver damage in rats].
Captopril, an inhibitor of angiotensin converting enzyme is widely used in the treatment of hypertension and congestive heart failure. It contains active sulfhydryl group and shares other structural feature with cysteine, the main substrate of glutathione. Experiments were undertaken to examine the effect of captopril on concentration of endogenous glutathione in the liver and to examine the ability of captopril to protect against paracetamol-induced hepatotoxicity. Single doses of captopril (30 mg/kg) given to male Sprague-Dawley rats produced a significant time dependent depletion of hepatic glutathione: at 3 h--16% (controls--10% as the effect of fasting; p less than 0.02), at 5 h--25% (controls--17%; p less than 0.02). Pretreatment of rats with single doses of captopril (30 mg/kg) 2 hours prior to administration of toxic doses of paracetamol (2500 mg/kg) produced a significant depletion of hepatic glutathione level as compared with animals without pretreatment with captopril (median: 2.95 mumol/g liver and 3.50 mumol/g liver, respectively; p less than 0.01). This was not accompanied by a difference in the hepatotoxic effect of paracetamol as assessed by histological staging of necrosis. Studies on covalent binding of paracetamol showed that neither captopril at the doses 30 mg/kg, nor penicillamine (20 mg/kg) affected covalent binding of paracetamol metabolites to cell protein. The results suggest that captopril despite its structural similarity to cysteine depletes hepatic glutathione level and does not protect against paracetamol hepatotoxicity.
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Kliniki Gastroenterologii i Przemiany Materii Centrum Medycznego Kształcenia, Podyplomowego, Warszawie.
D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D002216:Captopril / Q000008:administration & dosage / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000082:Acetaminophen; D002216:Captopril; D005978:Glutathione
Wpływ kaptoprilu na stezenie glutationu w watrobie i hepatotoksyczność paracetamolu u szczurów.