Potentiation of cisplatin-induced nephrotoxicity in rats by allopurinol.
Cisplatin (CDDP) is an effective chemotherapeutic agent used against various human malignancies. However, it induces nephrotoxicity, a severe side effect in which oxygen free radicals have been implicated to play an important role. The effect of allopurinol (Allp) given in a dose of 50 mg/kg subcutaneously (s.c.) for five days was examined on induced nephrotoxicity by a single dose of 5 mg/kg CDDP intraperitoneally (i.p.) in male wistar rats. Serum creatinine and blood urea nitrogen (BUN) concentrations were found significantly higher in the group given both Allp and CDDP than in the group given CDDP alone, p < 0.001, and histopathological examination showed more excessive degree of proximal tubular necrosis in the kidneys of animals given CDDP plus Allp than in those treated with CDDP alone. Increased renal lipid peroxidation, p < 0.001 associated with these pathological alterations suggested that oxidative stress may be involved in the potentiation of CDDP-induced nephrotoxicity by Allp.
Erdinç
M
M
Department of Pharmacology, Faculty of Medicine, University of Dicle, Diyarbakir, Turkey.
Erdinç
L
L
Nergiz
Y
Y
Işik
B
B
D000493:Allopurinol / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D004347:Drug Interactions; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D015227:Lipid Peroxidation; D008297:Male; D009336:Necrosis; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar
D000963:Antimetabolites; D000970:Antineoplastic Agents; D000493:Allopurinol; D002945:Cisplatin