Protective effect of S-(1,2-dicarboxyethyl)glutathione, an intrinsic tripeptide in liver, heart and lens, and its esters on acetaminophen-induced hepatotoxicity in rats.
The administration of acetaminophen (APAP, 500 mg/kg, i.p.) produced liver necrosis and increased aspartate aminotransaminase (AST) activity in serum. The pretreatment of S-(1,2-diethoxycarbonyl)glutathione isopropyl ester (DCE-Et-GS iPr, 0.5 mmol/kg, p.o.) prevented hepatic necrosis and the elevation of serum AST activity by 99.9%. DCE-Et-GS iPr inhibited APAP-induced hepatotoxicity much more strongly than reduced glutathione (GSH), DCE-GS and other esters of DCE-GS. To clarify this protective effect, the hepatic GSH concentration was determined 2h after APAP administration. It was found that the DCE-Et-GS iPr administration significantly inhibited the GSH depletion caused by APAP, suggesting that the protective effect of DCE-Et-GS iPr on APAP-induced hepatotoxicity was due, at least in part, to the retention of hepatic GSH level.
Sakaue
T
T
Senju Pharmaceutical Co., Ltd., Itami, Japan.
Matsumoto
S
S
Tsuboi
S
S
Ogata
K
K
Ohmori
S
S
D000082:Acetaminophen / Q000037:antagonists & inhibitors* / Q000633:toxicity; D018712:Analgesics, Non-Narcotic / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D007908:Lens, Crystalline / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D018712:Analgesics, Non-Narcotic; C041581:S-(1,2-dicarboxyethyl)glutathione; D000082:Acetaminophen; D001219:Aspartate Aminotransferases; D005978:Glutathione