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

由于黄嘌呤氧化酶衍生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中起重要作用，我们利用3-氨基-1,2,4-三唑灭活肝过氧化氢酶和体内脂多糖给药后大鼠肝脏中黄嘌呤氧化酶与黄嘌呤脱氢酶活性的比值研究了过氧化氢的生成。我们还研究了黄嘌呤氧化酶的有效抑制剂钨对脂多糖毒性的影响。给药后，大鼠肝脏过氧化氢产量增加，黄嘌呤脱氢酶向黄嘌呤氧化酶的蛋白水解转化增强。给大鼠喂食富含钨的饲料4周后，肝黄嘌呤氧化酶活性显著降低，脂多糖处理后细胞内过氧化氢产量的增加也明显减少。根据血清转氨酶水平和死亡率评估，富钨饮食也改善了肝损伤。这些发现表明，由黄嘌呤氧化酶产生的过氧化氢有助于脂多糖给药后全身毒性和肝损伤的发展。

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.