Possible mechanism responsible for allopurinol-nephrotoxicity: lipid peroxidation and systems of producing- and scavenging oxygen radicals.
In order to elucidate toxic and protective mechanisms responsible for allopurinol-induced nephrotoxicity in rats, we investigated changes in plasma creatinine concentration, renal lipid peroxidation, and renal activities of xanthine oxidase, superoxide dismutase and catalase, as enzymatic factors in producing and scavenging oxygen radicals. The rats received subcutaneous injections of allopurinol in a dose of 100 mg/kg body weight, once a day for 3 days. In comparison to the control rats, the following changes were observed in the allopurinol-administered rats: an increase in plasma creatinine concentration, increases in renal contents of malonaldehyde, hypoxanthine and xanthine, and an increase of renal activity of xanthine oxidase, and decreases in renal activities of superoxide dismutase and catalase. Peaks in these changes were observed coincidentally on the third day after the administration of the drug was started. Afterwards, these parameters all returned to the control levels. These results strongly suggested that the allopurinol nephrotoxicity was attributed to the increase of lipid peroxidation which had been caused both by an increase in the ability of producing the oxygen radicals and by a decrease in the ability of scavenging the radicals.
Department of Toxicology and Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Higashi-Nippon-Gakuen University, Hokkaido, Japan.
Y
Y
Suzuki
J
J
Sudo
D000493:Allopurinol / Q000633:toxicity*; D000818:Animals; D002374:Catalase / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D005609:Free Radicals; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism*; D008054:Lipid Peroxides / Q000096:biosynthesis*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000378:metabolism; D019820:Xanthine; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism
D005609:Free Radicals; D007042:Hypoxanthines; D008054:Lipid Peroxides; D014970:Xanthines; D019820:Xanthine; D019271:Hypoxanthine; D000493:Allopurinol; D003404:Creatinine; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D010100:Oxygen