Lauterburg Bernhard H
Department of Clinical Pharmacology, University of Bern, Bern, Switzerland.
Am J Ther. 2002 May-Jun;9(3):225-33. doi: 10.1097/00045391-200205000-00008.
A growing body of evidence indicates that glutathione (GSH) plays a vitally important role in cellular function. It detoxifies toxic metabolites of drugs and reactive oxygen species and regulates gene expression, apoptosis, and transmembrane transport of organic solutes. The maintenance of GSH homeostasis is essential for the organism to perform its many functions. The turnover of GSH is a dynamic process, and large quantities of GSH are synthesized per day from its precursor amino acids cysteine, glutamic acid, and glycine. Toxic doses of paracetamol deplete intracellular GSH and result in cell death by a combination of mechanisms, leading to necrosis and apoptosis, mainly in the liver. In clinical situations characterized by low GSH, the risk of toxicity from therapeutic doses of paracetamol may conceivably be increased. This toxicity has been reported in chronic alcoholics who have low intrahepatic GSH and who may have an induced enzyme system that generates the toxic metabolite of paracetamol. Considering the large number of alcoholics in our population and the widespread use of paracetamol, this must be a rare and essentially unpredictable occurrence. Except for anecdotal reports, there is no convincing evidence that other populations in which low GSH has been observed-such as patients with human immunodeficiency virus (HIV) infection or chronic hepatitis C, malnourished patients, and patients with cirrhosis-are at higher risk of experiencing adverse events from paracetamol.
越来越多的证据表明，谷胱甘肽（GSH）在细胞功能中起着至关重要的作用。它可使药物的有毒代谢产物和活性氧解毒，并调节基因表达、细胞凋亡和有机溶质的跨膜运输。维持GSH的内稳态对于机体发挥其多种功能至关重要。GSH的周转是一个动态过程，每天都有大量的GSH由其前体氨基酸半胱氨酸、谷氨酸和甘氨酸合成。对乙酰氨基酚的毒性剂量会消耗细胞内的GSH，并通过多种机制导致细胞死亡，主要在肝脏中引发坏死和凋亡。在GSH水平较低的临床情况下，治疗剂量的对乙酰氨基酚产生毒性的风险可能会增加。这种毒性在肝内GSH水平较低且可能具有诱导酶系统（该系统可生成对乙酰氨基酚的有毒代谢产物）的慢性酗酒者中已有报道。考虑到我国酗酒者数量众多以及对乙酰氨基酚的广泛使用，这必定是一种罕见且基本无法预测的情况。除了轶事报道外，没有令人信服的证据表明，其他观察到GSH水平较低的人群，如人类免疫缺陷病毒（HIV）感染者、慢性丙型肝炎患者、营养不良患者和肝硬化患者，服用对乙酰氨基酚时发生不良事件的风险更高。
