Role of reactive oxygen intermediates in lipopolysaccharide-mediated hepatic injury in the rat.
Because 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.
Takeyama
N
N
Department of Emergency and Critical Care Medicine, Kansai Medical University, Osaka, Japan.
Shoji
Y
Y
Ohashi
K
K
Tanaka
T
T
D000241:Adenosine / Q000378:metabolism; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D004032:Diet; D004798:Enzymes / Q000097:blood; D006861:Hydrogen Peroxide / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008107:Liver Diseases / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014414:Tungsten / Q000008:administration & dosage; D014968:Xanthine Dehydrogenase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D004798:Enzymes; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D000241:Adenosine; D014414:Tungsten