In vitro salicylate does not further impair aging-induced brain mitochondrial dysfunction

• Tipo: Artigo em Revista Científica Internacional
• Data: 2012

Autores

marques-aleixo, i (Autor) Outra; rocha-rodrigues, s (Autor) Outra; santos-alves, e (Autor) Outra; coxito, pm (Autor) Outra; passos, e (Autor) Outra; oliveira, pj (Autor) Outra; magalhaes, j (Autor) FADEUP; ascensao, a (Autor) FADEUP

Revista

Título: Toxicology

Vol. 302

Páginas: 51-59

ISSN: 0300-483X

Editora: Elsevier

Indexação

ISI Web of Knowledge - 5 Citações

Scopus - 5 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

Outras Informações

ID Authenticus: P-002-2DH

DOI: 10.1016/j.tox.2012.07.018

Abstract (EN): Aging and drug-induced side effects may contribute to the deterioration of mitochondrial bioenergetics in the brain. One hypothesis is that the combination of both deleterious stimuli accelerates the process of mitochondrial degradation, leading to progressive bioenergetic disruption. The hypothesis was tested by analyzing the isolated and combined effect of aging and salicylate, a vastly used anti-inflammatory drug, on isolated brain fractions in rats. Male Wistar rats were divided according to age in two groups: adult (n = 8, 19 weeks of age) and aged (n = 8, 106 weeks of age). In vitro endpoints of brain mitochondrial function including oxygen consumption and transmembrane electric potential (Delta psi) were evaluated in the absence and in the presence of salicylate (0.5 mM). Brain mitochondrial susceptibility to calcium-induced permeability transition pore (MPTP) was also assessed. Mitochondrial oxidative stress was determined by measuring aconitase and manganese-superoxide dismutase (SOD) activity, and content in sulfhydryl groups (-SH) and malondialdehyde (MDA). Mitochondrial content in apoptotic-related proteins Bax, Bcl-2 and cyclophilin D was determined by Western Blotting. Under basal, untreated, conditions, aging affected brain mitochondrial state 3 respiration, maximal Delta psi developed, ADP phosphorylation lag phase and calcium-induced MPTP. Interestingly, MDA decreased and Mn-SOD activity increased in the aged group. Brain mitochondrial Bcl-2 content decreased and Bax/Bcl-2 ratio increased in aged group. Salicylate incubation for 20 min increased lipid peroxidation in the aged group only and stimulated respiration during state 2, accompanied by decreased Delta psi, although both effects were independent of the animal age. We confirmed that both aging and salicylate per se impaired brain mitochondrial bioenergetics, although the combination of both does not seem to worsen the mitochondrial end-points studied.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9