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牛磺酸对环孢素A诱导的大鼠氧化应激和肝毒性的保护作用。

The protective effect of taurine against cyclosporine A-induced oxidative stress and hepatotoxicity in rats.

作者信息

Hagar Hanan H

机构信息

Department of Pharmacology, College of Medicine and KHUH, King Saud University, P.O. Box 2925, Riyadh 11461, Saudi Arabia.

出版信息

Toxicol Lett. 2004 Jul 15;151(2):335-43. doi: 10.1016/j.toxlet.2004.03.002.

Abstract

Cyclosporine A (CsA) is the immunosuppressor which is most frequently used in transplant surgery and in the treatment of autoimmune diseases. Oxidative stress has been implicated as one of the possible mechanisms of CsA-induced hepatotoxicity. The present investigation examined the ability of taurine as an antioxidant to protect against CsA-induced oxidative stress and hepatotoxicity. CsA hepatotoxicity was induced by subcutaneous injection of CsA at a dose of 20mg/kg body weight daily for 21 days. Hepatotoxicity was assessed by reduced serum total protein level and increased serum levels of gamma glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransaminase (AST). CsA treatment increased lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS) concentration and decreased reduced glutathione (GSH) content and activities of catalase and glutathione peroxidase (GSH-Px) in the rat liver. Taurine administration (1% in the drinking water) for 3 days before and concurrently during CsA injections improved liver functions, as indicated by decline of serum transaminases and GGT levels and elevation of serum total protein. Moreover, taurine significantly reduced hepatic TBARS and increased GSH content and catalase and GSH-Px activities in the hepatic tissue. These results indicate that taurine has a protective action against CsA hepatotoxicity and suggest that taurine may find clinical application against a variety of toxins where cellular damage is a consequence of reactive oxygen species.

摘要

环孢素A(CsA)是移植手术和自身免疫性疾病治疗中最常用的免疫抑制剂。氧化应激被认为是CsA诱导肝毒性的可能机制之一。本研究检测了牛磺酸作为抗氧化剂预防CsA诱导的氧化应激和肝毒性的能力。通过每天皮下注射20mg/kg体重的CsA,持续21天来诱导CsA肝毒性。通过血清总蛋白水平降低以及血清γ-谷氨酰转移酶(GGT)、丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)水平升高来评估肝毒性。CsA处理增加了以硫代巴比妥酸反应性物质(TBARS)浓度衡量的脂质过氧化,并降低了大鼠肝脏中还原型谷胱甘肽(GSH)含量以及过氧化氢酶和谷胱甘肽过氧化物酶(GSH-Px)的活性。在CsA注射前3天及注射期间同时给予牛磺酸(饮用水中含1%)改善了肝功能,表现为血清转氨酶和GGT水平下降以及血清总蛋白升高。此外,牛磺酸显著降低了肝脏中的TBARS,并增加了肝组织中的GSH含量以及过氧化氢酶和GSH-Px的活性。这些结果表明牛磺酸对CsA肝毒性具有保护作用,并提示牛磺酸可能在针对各种因活性氧导致细胞损伤的毒素方面找到临床应用。

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