Email updates

Keep up to date with the latest news and content from BMC Pharmacology and BioMed Central.

Open Access Research article

Peroxynitrite decomposition catalyst ameliorates renal damage and protein nitration in cisplatin-induced nephrotoxicity in rats

Yolanda I Chirino1, Rogelio Hernández-Pando2 and José Pedraza-Chaverrí1*

Author Affiliations

1 Departamento de Biología, Facultad de Química, Edificio B, Segundo Piso, Lab 209, Ciudad Universitaria, UNAM, México D.F. México

2 Departamento de Patología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" 14000, México, D.F. México

For all author emails, please log on.

BMC Pharmacology 2004, 4:20  doi:10.1186/1471-2210-4-20

Published: 30 September 2004

Abstract

Background

Oxidative stress is involved in cisplatin-nephrotoxicity. However, it has not completely established if reactive nitrogen species and nitrosative stress are involved in this experimental model. The purpose of this work was to study the role of peroxynitrite, a reactive nitrogen specie, in cisplatin-nephrotoxicity using the compound 5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato iron (III) (FeTPPS), a soluble complex able to metabolize peroxynitrite.

Results

In rats treated with cisplatin (a single intraperitoneal dose of 7.5 mg/kg body weight), renal nitrosative stress was made evident by the increase in 3-nitrotyrosine on day 3. In addition, cisplatin-induced nephrotoxicity was evident by the histological damage of proximal tubular cells and by the increase in (a) serum creatinine, (b) blood urea nitrogen, and (c) urinary excretion of N-acetyl-β-D-glucosaminidase and total protein. Cisplatin-induced nitrosative stress and nephrotoxicity were attenuated by FeTPPS-treatment (15 mg/kg body weight, intraperitoneally, every 12 hours for 3 days).

Conclusions

Nitrosative stress is involved in cisplatin-induced nephrotoxicity in rats. Our data suggest that peroxynitrite is involved, at least in part, in cisplatin-induced nephrotoxicity and protein nitration.