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

鉴于黄嘌呤氧化酶产生的活性氧中间产物可能在脂多糖介导的组织损伤的病理生理过程中起重要作用，我们研究了3-氨基-1，2，4-三氮唑灭活肝过氧化氢酶产生过氧化氢的作用，以及体内注射脂多糖后大鼠肝脏中黄嘌呤氧化酶/黄嘌呤脱氢酶活性的比值。我们还研究了黄嘌呤氧化酶的有效抑制剂钨对内毒素毒性的影响。大鼠肝脏经脂多糖处理后，过氧化氢生成量增加，黄嘌呤脱氢酶向黄嘌呤氧化酶的蛋白水解率增加。饲喂高钨饲料4周后，大鼠肝脏黄嘌呤氧化酶活性显著降低，细胞内过氧化氢生成增加的幅度也减弱。通过血清转氨酶水平和死亡率评估的肝脏损伤也通过富钨饮食得到改善。这些结果表明，黄嘌呤氧化酶产生的过氧化氢参与了脂多糖的全身毒性和肝损伤的形成。

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.