Caloric Restriction Is More Efficient than Physical Exercise to Protect from Cisplatin Nephrotoxicity via PPAR-Alpha Activation

Caloric Restriction Is More Efficient than Physical Exercise to Protect from Cisplatin Nephrotoxicity via PPAR-Alpha Activation

Author Estrela, Gabriel R. Autor UNIFESP Google Scholar
Wasinski, Frederick Autor UNIFESP Google Scholar
Batista, Rogerio O. Autor UNIFESP Google Scholar
Hiyane, Meire I. Google Scholar
Felizardo, Raphael J. F. Autor UNIFESP Google Scholar
Cunha, Flavia Autor UNIFESP Google Scholar
de Almeida, Danilo C. Autor UNIFESP Google Scholar
Malheiros, Denise M. A. C. Google Scholar
Camara, Niels O. S. Google Scholar
Barros, Carlos C. Google Scholar
Bader, Michael Google Scholar
Araujo, Ronaldo C. Autor UNIFESP Google Scholar
Abstract The antineoplastic drug cisplatin promotes renal injury, which limits its use. Protocols that reduce renal cisplatin toxicity will allow higher doses to be used in cisplatin treatment. Here, we compare physical exercise and caloric restriction (CR) as protocols to reduce cisplatin renal injury in mice. Male C57BL/6 were divided into four groups: Control, cisplatin, exercise + cisplatin, and 30% CR + cisplatin. Animals were injected with a single dose of cisplatin (20 mg/kg i.p.) and sacrificed 96 h after injection. Quantitative real time PCR, histological analyses, immunohistochemistry, and biochemical measurements were performed to investigate renal injury, necrosis, apoptosis, and inflammatory mechanisms. Both protocols protected against cisplatin renal injury, but CR was more effective in reducing uraemia and renal necrosis. The CR + Cisplatin group exhibited reduced serum IL-1 beta and INF-alpha levels. No differences were noted in the renal mRNA expression of cytokines. Both interventions reduced apoptosis, but only the CR + Cisplatin group decreased TNFR2 protein expression. PPAR-ci was activated in mice after CR. An antagonist of PPAR-alpha blocked the protective effect of CR. Both interventions attenuated the nephrotoxicity caused by cisplatin injection, but CR + Cisplatin showed a better response by modulating TNFR2. Moreover, part of the CR benefit depends on PPAR-alpha activation.
Keywords cisplatin nephrotoxicity
caloric restriction
xmlui.dri2xhtml.METS-1.0.item-coverage Lausanne
Language English
Sponsor FAPESP (Fundacao de Apoio a Pesquisa do Estado de Sao Paulo)
Grant number FAPESP: 2013/06207-6
FAPESP: 2015/20082-7
CAPES/DAAD: 427/15
Date 2017
Published in Frontiers In Physiology. Lausanne, v. 8, p. -, 2017.
ISSN 1664-042X (Sherpa/Romeo, impact factor)
Publisher Frontiers Media Sa
Extent -
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000395104400002

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