Hydrogen peroxide and ischemic renal injury: effect of catalase inhibition.
Although reactive oxygen species are believed to participate in postischemic renal injury, the actual chemical species involved and the role of endogenous scavenging systems in protecting against injury requires additional study. Hydrogen peroxide, which derives from superoxide radical, is toxic and also yields toxic hydroxyl radical. 3-amino-1,2,4-triazole reacts with catalase to form irreversibly inactivated catalase only in the presence of hydrogen peroxide. We made use of this chemical reaction both to determine whether inhibition of the hydrogen peroxide-scavenging enzyme catalase would influence ischemic renal injury and to measure hydrogen peroxide production rates after ischemia. Sprague-Dawley rats were given aminotriazole (100 mg/kg) one hour before 40 min of renal ischemia. Twenty-four h after ischemia GFR had decreased to 300 microL/min in control animals and to 50 microL/min in aminotriazole-treated animals. Histologic evidence of injury was also worse in catalase-inhibited animals. To measure hydrogen peroxide production rates aminotriazole was given 60 min before measurement of renal catalase activity. In control animals, aminotriazole caused a 53.4% decrease in catalase activity. In animals subjected to 40 min of ischemia plus either 10 or 60 min of reflow catalase activity decreased by 33.9 and 49.5% (not significantly different from control). Thus, when measured by this method total renal hydrogen peroxide production was considerable but was not increased by ischemia. However, in isolated proximal tubule segments 60 min of anoxia and 30 min of reoxygenation caused a 42% increase in H2O2 released into the incubation medium. In summary, inhibition of catalase before ischemia led to exacerbation of ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)
Paller
M S
MS
Department of Medicine, University of Minnesota, Minneapolis 55455.
D000640:Amitrole / Q000494:pharmacology*; D000818:Animals; D002374:Catalase / Q000037:antagonists & inhibitors*; D004789:Enzyme Activation / Q000187:drug effects; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000098:blood supply* / Q000201:enzymology; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism
D005609:Free Radicals; D006878:Hydroxides; D013481:Superoxides; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D002374:Catalase; D000640:Amitrole