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

Carvalho Rodrigues, Maria A., Santos, Neife A. G. dos, da Silva Faria, Marcia C., Rodrigues, Jairo Lisboa, Kinoshita, Angela, Baffa, Oswaldo, Antunes, Lusania M. Greggi, Barbosa, Fernando, Gobe, Glenda C. and Santos, Antonio Cardozo dos (2016) Carvedilol protects the kidneys of tumor-bearing mice without impairing the biodistribution or the genotoxicity of cisplatin. Chemico-Biological Interactions, 245 59-65. doi:10.1016/j.cbi.2015.12.020


Author Carvalho Rodrigues, Maria A.
Santos, Neife A. G. dos
da Silva Faria, Marcia C.
Rodrigues, Jairo Lisboa
Kinoshita, Angela
Baffa, Oswaldo
Antunes, Lusania M. Greggi
Barbosa, Fernando
Gobe, Glenda C.
Santos, Antonio Cardozo dos
Title Carvedilol protects the kidneys of tumor-bearing mice without impairing the biodistribution or the genotoxicity of cisplatin
Journal name Chemico-Biological Interactions   Check publisher's open access policy
ISSN 1872-7786
0009-2797
Publication date 2016-02-05
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.cbi.2015.12.020
Open Access Status Not Open Access
Volume 245
Start page 59
End page 65
Total pages 7
Place of publication Shannon, Clare Ireland
Publisher Elsevier Ireland
Collection year 2017
Language eng
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 anti-hypertensive 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.
Keyword Cisplatin
Carvedilol
Nephroprotection
Genotoxicity
Biodistribution
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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