Oxidative stress as a mechanism of chronic cadmium-induced hepatotoxicity and renal toxicity and protection by antioxidants
Oxidative stress as a mechanism of chronic cadmium-induced hepatotoxicity and renal toxicity and protection by antioxidants
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DOI：
10.1006/taap.1998.8586
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发表时间：
1999-02-01
影响因子：
3.8
通讯作者：
Zaman, K
中科院分区：
文献类型：
--
作者：
Shaikh, ZA;Vu, TT;Zaman, K
研究了氧化应激在慢性镉（Cd）中毒中的作用以及抗氧化剂的干预作用。成年雌性Sprague-Dawley大鼠皮下注射5 μ mol CdCl 2/kg/天，每周5次，持续22周。血清丙氨酸氨基转移酶和乳酸脱氢酶活性升高后9周的镉管理，表明肝损伤。在此期间还观察到肾毒性，表现为尿乳酸脱氢酶活性和蛋白质升高。慢性镉管理导致肝脏以及肾皮质谷胱甘肽水平逐渐上升。尽管如此，脂质过氧化增加，在这两个组织中，特别是在下半年的镉暴露期。在第5周结束时丁噻鲁胺磺酰亚胺给药后谷胱甘肽耗尽，或在第7周结束时氨基三唑抑制过氧化氢酶，导致在6小时内发生急性肾毒性。抗氧化剂N-乙酰半胱氨酸（50-100 mg/kg，sc），或维生素E（100-150 mg/kg，sc）与镉，从镉暴露的早期阶段开始，控制镉诱导的脂质过氧化反应，并保护动物免受肝脏和肾脏毒性。一种日本的保肝药，更强的新甘草酸C，含有甜菜碱，甘氨酸和半胱氨酸，也有效地减少慢性镉肾毒性。总之，氧化应激似乎在慢性镉诱导的肝脏和肾脏毒性中发挥了重要作用，因为抑制的抗氧化防御系统的组件加速和管理的抗氧化剂保护镉毒性。(C)北京：科学出版社.
The role of oxidative stress in chronic cadmium (Cd) toxicity and its prevention by cotreatment with antioxidants was investigated. Adult female Sprague-Dawley rats were injected sc with 5 mu mol CdCl2/kg/day, 5 times a week, for up to 22 weeks. Serum alanine amino transferase and lactate dehydrogenase activities were elevated after 9 weeks of Cd administration, indicating hepatic damage. Renal toxicity, indicated by elevation in urinary lactate dehydrogenase activity and protein, was also observed around this time. Chronic Cd administration resulted in a gradual rise in hepatic as well as renal cortex glutathione levels. In spite of this, lipid peroxidation increased in both tissues, particularly during the second half of the Cd exposure period. Depletion of glutathione following buthionine sulfoximine administration at the end of Week 5, or inhibition of catalase by aminotriazole at the end of Week 7, resulted in the development of acute nephrotoxicity within 6 h. Coadministration of antioxidants, N-acetylcysteine (50-100 mg/kg, sc), or vitamin E (100-150 mg/kg, sc) with Cd, starting from the early phases of Cd exposure, controlled Cd-induced lipid peroxidation and protected the animals against hepatic as well as renal toxicity. A Japanese hepatoprotective drug, Stronger Neo-Minophagen C, containing glycyrrhizin, glycine, and cysteine, was also effective in reducing the chronic Cd nephrotoxicity. In conclusion oxidative stress appears to play a major role in chronic Cd-induced hepatic and renal toxicity since inhibition of components of the antioxidant defense system accelerated and administration of antioxidants protected against Cd toxicity. (C) 1999 Academic Press.