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Reactive oxygen metabolites in endotoxin-induced acute renal failure in rats

1990; Elsevier BV; Volume: 38; Issue: 6 Linguagem: Inglês

10.1038/ki.1990.322

1523-1755

Patrick D. Walker, Sudhir V. Shah,

Renal function and acid-base balance

Reactive oxygen metabolites In endotoxin-induced acute renal failure in rats.Based on recent reports that reactive oxygen metabolites may play a role in endotoxin-induced injury in other tissues, we postulated that reactive oxygen metabolites may be important mediators of endotoxininduced acute renal failure.Superoxide dismutase, a scavenger of superoxide, or catalase, which destroys hydrogen peroxide, did not protect against endotoxin-induced renal failure.Similarly, neither the hydroxyl radical scavenger dimethylthiourea nor the iron chelator deferoxamine (which presumably would act by preventing the generation of hydroxyl radical via the iron-catalyzed Haber-Weiss reaction) prevented the endotoxin-induced fall in renal function.In separate experiments, we found no increase in renal cortical lipid peroxidation (a marker of reactive oxygen metabolite-mediated tissue injury) in endotoxin-treated rats, providing further evidence against a role for reactive oxygen metabolites in endotoxin-induced renal injury.Finally, using the aminotriazole-induced inhibition of catalase (a measure of in vivo changes in the hydrogen peroxide generation) we found no evidence of enhanced hydrogen peroxide generation in the renal cortex in endotoxin-treated rats.Taken together, the data from these three separate experimental approaches suggest that reactive oxygen metabolites are not important mediators of endotoxin-induced acute renal failure.Reactive oxygen metabolites (ROM), including free radicals (for example, superoxide anion and hydroxyl radical) and other toxic oxygen metabolites (such as, hydrogen peroxide and hypochlorous acid) have been postulated to be important mediators of several models of immune-mediated toxic and ischemic tissue injury [1-8].Specifically, several recent studies suggest that reactive oxygen metabolites may have an important role in the pathophysiology of renal disease [9][10][11][12][13][14][15][16][17].In particular, enhanced in vivo generation of hydrogen peroxide has been demonstrated in two models of acute renal failure [16,18], and scavengers of ROM andiron chelators (presumably by preventing the generation of hydroxyl radical by the ironcatalyzed Haber-Weiss reaction) have been shown to be protective in ischemic [5], aminoglycoside-induced [17] and in glycerol-induced acute renal failure [12,15].There have been extensive studies of the biological effects of endotoxin and the underlying pathogenetic mechanism(s) leading to endotoxin related end-organ failure [reviewed in 19].Although there is conflicting data, recent reports have sug-