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

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dc.citation.volume8
dc.contributor.authorEstrela, Gabriel R. [UNIFESP]
dc.contributor.authorWasinski, Frederick [UNIFESP]
dc.contributor.authorBatista, Rogerio O. [UNIFESP]
dc.contributor.authorHiyane, Meire I.
dc.contributor.authorFelizardo, Raphael J. F. [UNIFESP]
dc.contributor.authorCunha, Flavia [UNIFESP]
dc.contributor.authorde Almeida, Danilo C. [UNIFESP]
dc.contributor.authorMalheiros, Denise M. A. C.
dc.contributor.authorCamara, Niels O. S.
dc.contributor.authorBarros, Carlos C.
dc.contributor.authorBader, Michael
dc.contributor.authorAraujo, Ronaldo C. [UNIFESP]
dc.coverageLausanne
dc.date.accessioned2020-07-17T14:02:40Z
dc.date.available2020-07-17T14:02:40Z
dc.date.issued2017
dc.description.abstractThe 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.en
dc.description.affiliationUniv Fed Sao Paulo, Dept Biofis, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Med, Disciplina Nefrol, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Inst Ciencias Biomed, Dept Immunol, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Dept Clin Med, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Pelotas, Escola Nutr, Dept Nutr, Pelotas, Brazil
dc.description.affiliationMax Delbruck Ctr Mol Med, Berlin, Germany
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biofis, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Med, Disciplina Nefrol, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFAPESP (Fundacao de Apoio a Pesquisa do Estado de Sao Paulo)
dc.description.sponsorshipCAPES/DAAD
dc.description.sponsorshipIDFAPESP: 2013/06207-6
dc.description.sponsorshipIDFAPESP: 2015/20082-7
dc.description.sponsorshipIDCAPES/DAAD: 427/15
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.3389/fphys.2017.00116
dc.identifier.citationFrontiers In Physiology. Lausanne, v. 8, p. -, 2017.
dc.identifier.doi10.3389/fphys.2017.00116
dc.identifier.fileWOS000395104400002.pdf
dc.identifier.issn1664-042X
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54940
dc.identifier.wosWOS:000395104400002
dc.language.isoeng
dc.publisherFrontiers Media Sa
dc.relation.ispartofFrontiers In Physiology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectcisplatin nephrotoxicityen
dc.subjectinflammationen
dc.subjectcaloric restrictionen
dc.subjectexerciseen
dc.subjectPPAR-alphaen
dc.titleCaloric Restriction Is More Efficient than Physical Exercise to Protect from Cisplatin Nephrotoxicity via PPAR-Alpha Activationen
dc.typeinfo:eu-repo/semantics/article
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