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Food Chem Toxicol. 2017 Sep;107(Pt A):226-236. doi: 10.1016/j.fct.2017.06.047. Epub 2017 Jun 30.

Differential effect of quercetin on cisplatin-induced toxicity in kidney and tumor tissues.

Author information

1
Unidad de Toxicología, University of Salamanca, Spain.
2
Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), Salamanca, Spain; Instituto de Estudios de Ciencias de la Salud de Castilla y León (IECSCYL), Soria, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
3
Grupo de Investigación en Polifenoles, Unidad de Nutrición y Bromatología, University of Salamanca, Spain.
4
Unidad de Toxicología, University of Salamanca, Spain; Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
5
Cellular Biology in Renal Diseases Laboratory, Instituto de Investigación Sanitaria Fundación Jimenez Diaz, Universidad Autónoma Madrid, Madrid, Spain.
6
Institut für Zellbiologie, Universitätsklinikum Essen, Germany.
7
Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
8
Unidad de Toxicología, University of Salamanca, Spain; Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain. Electronic address: amorales@usal.es.

Abstract

Strategies to minimize the nephrotoxicity of platinated antineoplastics without affecting its antitumour efficacy are strongly necessary to improve the pharmacotoxicological profile of these drugs. The natural flavonoid quercetin has been shown to afford nephroprotection without affecting cisplatin antitumour effect. The purpose of the present study has been to assess the differential mechanisms of action of cisplatin and quercetin on kidney and tumour tissues that could explain these effects. Wistar rats bearing subcutaneous tumours were treated with cisplatin and quercetin (and the appropriate controls). Tumour size and renal function evolution was monitored during 6 days. Platinum and quercetin content were also determined in both tissues. All the parameters studied, including blood supply, inflammation, apoptosis, critical MAPK signaling and oxidative stress in the cisplatin-treated animals are almost normalized by quercetin in the kidneys, but unaffected in the tumours. Our results suggest that in a cancer model in vivo, the protection exerted by quercetin on cisplatin nephrotoxicity is related to its antioxidant, vascular, anti-inflammatory and antiapoptotic effects, but these properties do not affect the mechanisms responsible for the antitumour effect of cisplatin.

KEYWORDS:

Antitumour activity; Cisplatin; Cytoprotection; Kidney injury; Quercetin; Rats

PMID:
28669851
DOI:
10.1016/j.fct.2017.06.047
[Indexed for MEDLINE]

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