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Role of reactive oxygen intermediates in lipopolysaccharidemediated hepatic injury in the rat

活性氧中间体在脂多糖介导的大鼠肝损伤中的作用

基本信息

批准号：
05671034
负责人：
TAKEYAMA Naoshi
金额：
$ 1.41万
依托单位：
Kansai Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

项目摘要

Since reactive oxygen intermediates derived from xanthine oxidase may have an important role in the pathophysiology of lipopolysaccharide-mediated tissue injury, we studied hydrogen peroxide generation using 3-amino-1,2,4-triazole inactivation of hepatic catalase and the ratio of xanthine oxidase to xanthine dehydrogenase activity in rat livers after in vivo lipopolysaccharide administration. We also studied the effect of tungsten, a potent inhibitor of xanthine oxidase, on the toxicity of lipopolysaccharide. There was increased hydrogen peroxide production and enhanced proteolytic conversion from xanthine dehydrogenase to xanthine oxidase in rat livers after lipopolysaccharide administration. Feeding rats a tungsten-rich diet for 4 weeks greatly diminished hepatic xanthine oxidase activity and lessened the rise in intracellular hydrogen peroxide production after lipopolysaccharide treatment. Liver damage, as assessed by the serum transaminase levels and mortality, was also ameliorated by the tungsten-rich diet. These findings suggest that hydrogen peroxide derived from xanthine oxidase contributes to the development of systemic toxicity and liver damage after lipopolysaccharide administration.

由于来自黄嘌呤氧化酶的活性氧中间体可能在脂多糖介导的组织损伤的病理生理学中起重要作用，我们研究了过氧化氢的产生，使用3-氨基-1，2，4-三唑灭活肝过氧化氢酶和黄嘌呤氧化酶的比例，黄嘌呤脱氢酶活性在大鼠肝脏后，在体内脂多糖管理。我们还研究了一种有效的黄嘌呤氧化酶抑制剂钨对脂多糖毒性的影响。有增加过氧化氢的生产和增强黄嘌呤脱氢酶黄嘌呤氧化酶在大鼠肝脏的蛋白水解转化后脂多糖管理。喂养大鼠4周的富钨饮食大大降低了肝黄嘌呤氧化酶的活性，并减少了脂多糖治疗后细胞内过氧化氢的产生上升。通过血清转氨酶水平和死亡率评估的肝损伤也通过富钨饮食得到改善。这些发现表明，来自黄嘌呤氧化酶的过氧化氢有助于脂多糖给药后全身毒性和肝脏损伤的发展。