[Effects of allopurinol for oxidative injury of cisplatin-induced nephrotoxicity in mice].
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.
Namikawa
K
K
Department of Clinical Chemistry, Faculty of Pharmaceutical Sciences, Kinki University, Osaka, Japan.
Hirai
K
K
Kitano
T
T
Tanaka
I
I
Miyauchi
K
K
Minami
T
T
Okazaki
Y
Y
Kadota
E
E
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051379:Mice
D000970:Antineoplastic Agents; D016166:Free Radical Scavengers; D000493:Allopurinol; D005978:Glutathione; D002945:Cisplatin