Sakaue T, Matsumoto S, Tsuboi S, Ogata K, Ohmori S
Senju Pharmaceutical Co., Ltd., Itami, Japan.
Biol Pharm Bull. 1996 Sep;19(9):1216-9. doi: 10.1248/bpb.19.1216.
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.
给予对乙酰氨基酚（APAP，500毫克/千克，腹腔注射）会导致肝坏死，并使血清中天冬氨酸转氨酶（AST）活性升高。预先给予S-(1,2-二乙氧羰基)谷胱甘肽异丙酯（DCE-Et-GS iPr，0.5毫摩尔/千克，口服）可预防肝坏死，并使血清AST活性升高受到99.9%的抑制。DCE-Et-GS iPr抑制APAP诱导的肝毒性的作用比还原型谷胱甘肽（GSH）、DCE-GS及DCE-GS的其他酯类要强得多。为阐明这种保护作用，在给予APAP 2小时后测定肝脏GSH浓度。结果发现，给予DCE-Et-GS iPr可显著抑制APAP引起的GSH耗竭，这表明DCE-Et-GS iPr对APAP诱导的肝毒性的保护作用至少部分归因于肝脏GSH水平的维持。
