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British Journal of Experimental Pathology logoLink to British Journal of Experimental Pathology
. 1985 Feb;66(1):67–78.

Hepatic necrosis and glutathione depletion in captopril-treated mice.

T R Helliwell, J H Yeung, B K Park
PMCID: PMC2041016  PMID: 3882119

Abstract

Captopril (CP) is an angiotensin-converting enzyme inhibitor whose metabolism involves endogenous thiols which may be depleted at high doses of CP. Following intraperitoneal administration of CP (50-300 mg/kg), dose-dependent depletion of hepatic glutathione, increased serum transaminase (SGPT) levels and hepatic necrosis were observed. The hepatic necrosis observed was either subcapsular or parenchymal in distribution. Both types of necrosis showed a dose-dependent increase in severity but with a large inter-animal variation. The patterns of necrosis observed with CP are different from the necrosis caused by paracetamol. Oral CP (300 mg/kg) caused parenchymal necrosis in only one animal. It is suggested that subcapsular necrosis may be due to the direct effect of i.p. captopril whereas parenchymal necrosis may be a consequence of hepatic GSH depletion.

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