The potential protective role of alpha-lipoic acid against acetaminophen-induced hepatic and renal damage
The potential protective role of alpha-lipoic acid against acetaminophen-induced hepatic and renal damage
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DOI：
10.1016/j.tox.2007.10.010
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发表时间：
2008-01-20
期刊：
影响因子：
4.5
通讯作者：
Farrag, Magda M. Y.
中科院分区：
文献类型：
--
作者：
Abdel-Zaher, Ahmed O.;Abdel-Hady, Randa H.;Farrag, Magda M. Y.
研究了α-硫辛酸（α-LA）对对乙酰氨基酚（APAP）诱导的大鼠肝肾毒性的潜在保护作用。用α-LA（100 mg/kg）经口预处理大鼠，通过生化测量和组织病理学检查评估，可显著防止急性口服毒性剂量的APAP（2.5 g/kg）诱导的肝毒性和肾毒性。α-LA预处理的动物均未因急性毒性剂量的APAP而死亡。与此同时，APAP诱导的一氧化氮（NO）的产生和氧化应激的深刻升高，证明了增加脂质过氧化水平，谷胱甘肽过氧化物酶（GSH-Px）的活性和细胞内还原型谷胱甘肽（GSH）水平的消耗，在肝脏和肾脏，抑制预处理与α-LA。同样，每天用较小剂量的α-LA（25 mg/kg）同时用较小毒性剂量的APAP（750 mg/kg）治疗大鼠1周，可防止APAP诱导的肝毒性和肾毒性。这种治疗还完全预防了APAP诱导的死亡率，并显着抑制了APAP诱导的肝和肾组织NO过量产生和氧化应激。这些结果提供的证据表明，抑制NO的过度生产和维持细胞内的抗氧化状态可能发挥关键作用的α-LA对APAP诱导的肝和肾损伤的保护作用。(C)2007爱思唯尔爱尔兰有限公司保留所有权利。
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.