Carvedilol efficiently protects kidneys without affecting the antitumor efficacy of cisplatin in mice

Carvalho Rodrigues, Maria A., da Silva Faria, Marcia C., dos Santos, Neife A. G., Gobe, Glenda C. and dos Santos, Antonio Cardozo (2013) Carvedilol efficiently protects kidneys without affecting the antitumor efficacy of cisplatin in mice. Chemico-Biological Interactions, 206 1: 90-99. doi:10.1016/j.cbi.2013.08.015


Author Carvalho Rodrigues, Maria A.
da Silva Faria, Marcia C.
dos Santos, Neife A. G.
Gobe, Glenda C.
dos Santos, Antonio Cardozo
Title Carvedilol efficiently protects kidneys without affecting the antitumor efficacy of cisplatin in mice
Journal name Chemico-Biological Interactions   Check publisher's open access policy
ISSN 0009-2797
1872-7786
Publication date 2013-10
Sub-type Article (original research)
DOI 10.1016/j.cbi.2013.08.015
Volume 206
Issue 1
Start page 90
End page 99
Total pages 10
Place of publication Shannon, Co. Clare, Ireland
Publisher Elsevier
Collection year 2014
Language eng
Abstract Cisplatin is an effective anticancer drug which has been used to treat a wide range of tumors for the last 30 years. However, its use is associated with nephrotoxicity. Protective strategies have been reported, but their impact on the antitumor activity of cisplatin has not been clarified. We have previously reported the protective potential of carvedilol against cisplatin nephrotoxicity in tumor-free rats. Therefore, in the present study we used a tumor-bearing model to investigate the impact of carvedilol on the antitumor activity of cisplatin. The renal damage induced by cisplatin and the protective effect of carvedilol were demonstrated by the levels of blood urea nitrogen and plasma creatinine as well as by renal histopathology and immunohistochemistry. The mechanism of protection was associated with significantly decreased (i) oxidative stress markers, (ii) Bax expression, (iii) caspase-3 activity and (iv) TUNEL labeling for apoptosis. More importantly, evaluation of tumor mass, tumor remission rate and the survival curve showed that carvedilol did not impair the antitumor action of cisplatin. These findings suggest that the mechanisms underlying the nephrotoxic and the antitumor activity of cisplatin might be different. This is the first study to report such findings. Compared to other reported potential cytoprotectors against cisplatin-induced nephrotoxicity, carvedilol stands out due to the fact that it is already clinically-employed and well tolerated by the patients. Based on these features and on the present findings, carvedilol is a very promising candidate for future clinical trials as nephroprotector in patients treated with cisplatin.
Keyword Cisplatin
Carvedilol
Kidneys
Nephrotoxicity
Sarcoma-180
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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