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 endotoxin-induced 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.
Walker
P D
PD
Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana.
Shah
S V
SV
D058186:Acute Kidney Injury / Q000209:etiology* / Q000517:prevention & control; D000818:Animals; D003676:Deferoxamine / Q000627:therapeutic use*; D004731:Endotoxins / Q000633:toxicity*; D016166:Free Radical Scavengers; D006861:Hydrogen Peroxide / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000627:therapeutic use*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000627:therapeutic use
D004731:Endotoxins; D016166:Free Radical Scavengers; C038983:1,3-dimethylthiourea; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D013890:Thiourea; D003676:Deferoxamine