Protective effects of apocynin against cisplatin-induced oxidative stress and nephrotoxicity.
Cis-diamminedichloroplatinum (II) (cisplatin) is an effective chemotherapeutic agent successfully used in the treatment of a wide range of tumors; however, nephrotoxicity has restricted its clinical use. Several studies have shown that reactive oxygen species are involved in cisplatin-induced nephrotoxicity, including hydrogen peroxide, hydroxyl radical and superoxide anion (O(2)(-)). The source of O(2)(-) in cisplatin-induced renal damage has not been established. The aim of this study was to investigate if NADPH oxidase is involved in cisplatin-induced nephrotoxicity using apocynin, a widely used NADPH oxidase inhibitor. Rats were studied 3 days after a single injection of cisplatin (7.5mg/kg, i.p.). Apocynin was given in the drinking water (2g/L) 7 days before and 3 days after cisplatin injection. Apocynin treatment was able to ameliorate the renal histological damage and the increase in blood urea nitrogen, serum creatinine, and urinary excretion of total protein, N-acetyl-beta-d-glucosaminidase and glutathione-S-transferase induced by cisplatin. In addition, the protective effect of apocynin was associated with the amelioration of cisplatin-induced oxidative and nitrosative stress. Our data suggest that O(2)(-) derived from NADPH oxidase triggers some of the side effects due to cisplatin administration.
Chirino
Yolanda I
YI
Facultad de Química, Departamento de Biología, Edificio F, Segundo Piso, Laboratorio 209, Universidad Nacional Autónoma de México, 04510 México D.F., Mexico.
Sánchez-González
Dolores Javier
DJ
Martínez-Martínez
Claudia Maria
CM
Cruz
Cristino
C
Pedraza-Chaverri
José
J
D000098:Acetophenones / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D002945:Cisplatin / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007677:Kidney Function Tests; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D000098:Acetophenones; D000975:Antioxidants; D008054:Lipid Peroxides; D008315:Malondialdehyde; C056165:acetovanillone; D002945:Cisplatin