Evidence suggesting a role for hydroxyl radical in glycerol-induced acute renal failure.
Reactive oxygen metabolites, in particular hydroxyl radical, have been shown to be important mediators of tissue injury in several models of acute renal failure. The aim of the present study was to examine the role of hydroxyl radical in glycerol-induced acute renal failure, a model for myoglobinuric renal injury. Rats injected with glycerol alone (8 mg/kg im following dehydration for 24 h) developed significant renal failure compared with dehydrated controls. Rats treated with glycerol and a hydroxyl radical scavenger, dimethylthiourea (DMTU), had significantly lower blood urea nitrogen (BUN) and creatinine. In contrast, urea, which is chemically similar to DMTU but is not a hydroxyl radical scavenger, provided no protection. In addition, DMTU prevented the glycerol-induced rise in renal cortical malondialdehyde content (a measure of lipid peroxidation that serves as a marker of free radical-mediated tissue injury). A second hydroxyl radical scavenger, sodium benzoate, had a similar protective effect on renal function (as measured by both BUN and creatinine). Because the generation of hydroxyl radical in biological systems requires the presence of a trace metal such as iron, we also examined the effect of the iron chelator, deferoxamine on glycerol-induced renal failure. Deferoxamine was also protective. The interventional agents were also associated with a marked reduction in histological evidence of renal damage. The protective effects of two hydroxyl radical scavengers as well as an iron chelator implicate a role for hydroxyl radical in glycerol-induced acute renal failure.
Shah
S V
SV
Department of Medicine (Nephrology), Tulane University School of Medicine, New Orleans, Louisiana 70112.
Walker
P D
PD
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005609:Free Radicals; D005990:Glycerol; D006878:Hydroxides / Q000378:metabolism*; D017665:Hydroxyl Radical; D007668:Kidney / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013890:Thiourea / Q000031:analogs & derivatives / Q000627:therapeutic use
D005609:Free Radicals; D006878:Hydroxides; D017665:Hydroxyl Radical; C038983:1,3-dimethylthiourea; D003404:Creatinine; D013890:Thiourea; D005990:Glycerol