Carvedilol protects the kidneys of tumor-bearing mice without impairing the biodistribution or the genotoxicity of cisplatin

Author(s)

Carvalho Rodrigues, Maria A. ^[1] ; dos Santos, Neife A. G. ^[2] ; da Silva Faria, Marcia C. ^[3] ; Rodrigues, Jairo Lisboa ^[3] ; Kinoshita, Angela ^[4] ; Baffa, Oswaldo ^[4] ; Greggi Antunes, Lusania M. ^[2] ; Barbosa, Jr., Fernando ^[2] ; Gobe, Glenda C. ^[5] ; dos Santos, Antonio Cardozo ^[2]

Affiliation

^[1] Ctr Univ Distrito Fed, UDF, SEP, SEP SUL Conj A EQ704 904, BR-70390045 Brasilia, DF - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, Av Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] UFVJM, Campus Mucuri, Teofilo Otoni MG, Rua Cruzeiro, 01 Ja, BR-39803371 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Dept Fis, Fac Filosofia Ciencias & Letras Ribeirao Preto, Ave Cafe S-N, BR-14040901 Ribeirao Preto, SP - Brazil

^[5] Univ Queensland, Sch Med, Ctr Kidney Dis Res, Princess Alexandra Hosp, Brisbane, Qld 4102 - Australia

• Document type: Journal article
• Source: Chemico-Biological Interactions; v. 245, p. 59-65, FEB 5 2016.
• Web of Science Citations: 2

Abstract

Cisplatin (Cisp) is an effective antitumor drug; however, it causes severe nephrotoxicity. Minimization of renal toxicity is essential, but the interference of nephroprotective agents, particularly antioxidants, with the antitumor activity of cisplatin is a general concern. We have recently demonstrated that the antihypertensive and antioxidant drug carvedilol (CV) protects against the renal damage and increases the survival of tumor-bearing mice without impairing the tumor reduction by cisplatin. So far, reports on the antioxidant mechanism of CV are controversial and there are no data on the impact of CV on the antitumor mechanisms of cisplatin. Therefore, this study addresses the effect of CV on mechanisms underlying the tumor control by cisplatin. CV did not interfere with the biodistribution or the genotoxicity of cisplatin. We also addressed the antioxidant mechanisms of CV and demonstrated that it does not neutralize free radicals, but is an efficient chelator of ferrous ions that are relevant catalyzers in cisplatin nephrotoxicity. The present data suggest that oxidative damage and genotoxicity play different roles in the toxicity of cisplatin on kidneys and tumors and therefore, some antioxidants might be safe as chemoprotectors. Altogether, our studies provide consistent evidence of the beneficial effect of CV on animals treated with cisplatin and might encourage clinical trials. (C) 2016 Elsevier Ireland Ltd. All rights reserved. (AU)

• FAPESP's process: 09/10583-8 - Evaluation of the interference of the antioxidant effect of carvedilol, a potential nephroprotective agent, on cisplatin antitumoral activity
• Grantee: Maria Augusta Carvalho Rodrigues
• Support Opportunities: Scholarships in Brazil - Doctorate