Artículos de revistas
Protective effects of L-carnitine and piracetam against mitochondrial permeability transition and PC3 cell necrosis induced by simvastatin
Registro en:
European Journal Of Pharmacology. Elsevier Science Bv, v. 701, n. 41699, n. 82, n. 86, 2013.
0014-2999
WOS:000315709100012
10.1016/j.ejphar.2013.01.001
Autor
Costa, RAP
Fernandes, MP
de Souza-Pinto, NC
Vercesi, AE
Institución
Resumen
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Mitochondrial oxidative stress followed by membrane permeability transition (MPT) has been considered as a possible mechanism for statins cytotoxicity. Statins use has been associated with reduced risk of cancer incidence, especially prostate cancer. Here we investigated the pathways leading to simvastatin-induced prostate cancer cell death as well as the mechanisms of cell death protection by L-carnitine or piracetam. These compounds are known to prevent and/or protect against cell death mediated by oxidative mitochondrial damage induced by a variety of conditions, either in vivo or in vitro. The results provide evidence that simvastatin induced MPT and cell necrosis were sensitive to either L-carnitine or piracetam in a dose-dependent fashion and mediated by additive mechanisms. When combined, L-carnitine and piracetam acted at concentrations significantly lower than they act individually. These results shed new light into both the cytotoxic mechanisms of statins and the mechanisms underlying the protection against MPT and cell death by the compounds L-carnitine and piracetam. (C) 2013 Elsevier B.V. All rights reserved. 701 41699 82 86 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Biolab Sanus Farmaceutica Ltda (convenio Biolab/UNICAMP) [4198] Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Biolab Sanus Farmaceutica Ltda (convenio Biolab/UNICAMP) [4198]