The potential protective role of alpha-lipoic acid against acetaminophen-induced hepatic and renal damage

被引：108

作者：

Abdel-Zaher, Ahmed O. ^{[1
]}

Abdel-Hady, Randa H. ^{[2
]}

Mahmoud, Madeha M. ^{[3
]}

Farrag, Magda M. Y. ^{[1
]}

机构：

[1] Assiut Univ, Fac Sci, Dept Pharmacol, Assiut, Egypt

[2] Assiut Univ, Fac Med, Dept Forens Med & Toxicol, Assiut, Egypt

[3] Assiut Univ, Fac Med, Dept Histol, Assiut, Egypt

来源：

TOXICOLOGY | 2008年 / 243卷 / 03期

关键词：

acetaminophen; alpha-lipoic acid; nitric oxide; glutathione;

D O I：

10.1016/j.tox.2007.10.010

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The potential protective role of alpha-lipoic acid (alpha-LA) in acetaminophen (APAP)-induced hepatotoxicity and nephrotoxicity was investigated in rats. Pretreatment of rats with alpha-LA (100 mg/kg) orally protected markedly against hepatotoxicity and nephrotoxicity induced by an acute oral toxic dose of APAP (2.5 g/kg) as assessed by biochemical measurements and by histopathological examination. None of alpha-LA pretreated animals died by the acute toxic dose of APAP. Concomitantly, APAP-induced profound elevation of nitric oxide (NO) production and oxidative stress, as evidenced by increasing of lipid peroxidation level, reducing of glutathione peroxidase (GSH-Px) activity and depleting of intracellular reduced glutathione (GSH) level in liver and kidney, were suppressed by pretreatment with alpha-LA. Similarly, daily treatment of rats with a smaller dose of alpha-LA (25 mg/kg) concurrently with a smaller toxic dose of APAP (750 mg/kg) for 1 week protected against APAP-induced hepatotoxicity and nephrotoxicity. This treatment also completely prevented APAP-induced mortality and markedly inhibited APAP-induced NO overproduction and oxidative stress in hepatic and renal tissues. These results provide evidence that inhibition of NO overproduction and maintenance of intracellular antioxidant status may play a pivotal role in the protective effects of alpha-LA against APAP-induced hepatic and renal damage. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

引用

页码：261 / 270

页数：10

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