The effects of allopurinol (Allop) on the lipid peroxidation in the nephrotoxicity of an antitumor drug, cisplatin (CDDP) were studied in mice. CDDP was administered intraperitoneally to two groups (CDDP+Allop group and CDDP+CMC-Na group) at single doses of 10 mg/kg, and mice were sacrificed 3 days after CDDP administration. The body weights of the CDDP-administered group gradually decreased to approximately 78% of the values of the control group (saline+Allop group and saline+CMC-Na group) within 3 days. Plasma urea nitrogen and creatinine, especially in the CDDP+Allop group, increased after 3 days. Lipid peroxides in the blood and kidney were monitored by measuring the production of malondialdehyde (MDA), which increased in the CDDP+CMC-Na group. On the other hand, MDA levels in the CDDP+Allop group increased in the kidney but remained unchanged in the blood. Changes were observed in tissue glutathione (reduced form, GSH; oxidized form, GSSG) levels in the CDDP+Allop group but not in the CDDP+CMC-Na group. Histomorphological examination demonstrated the degeneration of the proximal tubuli in the CDDP-administered groups. Especially in the CDDP+Allop group, the increase of mesangium cells in the glomeruli was observed. From these results, it was suggested that Allop was not able to inhibit CDDP-induced lipid peroxidation in the kidney, and the kidney function became more severely impaired by the administration of Allop.
