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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Front+Physiol
2017 ; 8
(ä): 116
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Caloric Restriction Is More Efficient than Physical Exercise to Protect from
Cisplatin Nephrotoxicity via PPAR-Alpha Activation
#MMPMID28303105
Estrela GR
; Wasinski F
; Batista RO
; Hiyane MI
; Felizardo RJ
; Cunha F
; de Almeida DC
; Malheiros DM
; Câmara NO
; Barros CC
; Bader M
; Araujo RC
Front Physiol
2017[]; 8
(ä): 116
PMID28303105
show ga
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? and TNF-? 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-? was
activated in mice after CR. An antagonist of PPAR-? 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-? activation.