Protective effect of acetyl-L-carnitine and alpha-lipoic acid against the acute toxicity of diepoxybutane to human lymphocytes

• Tipo: Artigo em Revista Científica Internacional
• Data: 2011

Autores

Filipa Ponte (Autor) Outra; Felix Carvalho (Autor) FFUP; Beatriz Porto (Autor) ICBAS

Revista

Título: Toxicology

Vol. 289

Páginas: 52-58

ISSN: 0300-483X

Editora: Elsevier

Indexação

ISI Web of Knowledge - 7 Citações

Scopus - 13 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

Outras Informações

ID Authenticus: P-002-KED

DOI: 10.1016/j.tox.2011.07.009

Abstract (EN): The biotransformation and oxidative stress may contribute to 1,2:3,4-diepoxybutane (DEB)-induced toxicity to human lymphocytes of Fanconi Anemia (FA) patients. Thus, the identification of putative inhibitors of bioactivation, as well as the determination of the protective role of oxidant defenses, on DEB-induced toxicity, can help to understand what is failing in FA cells. In the present work we studied the contribution of several biochemical pathways for DEB-induced acute toxicity in human lymphocyte suspensions, by using inhibitors of epoxide hydrolases, inhibitors of protective enzymes as glutathione S-transferase and catalase, the depletion of glutathione (GSH), and the inhibition of protein synthesis: and a variety of putative protective compounds, including antioxidants, and mitochondria I protective agents. The present study reports two novel findings: (i) it was clearly evidenced, for the first time, that the acute exposure of freshly isolated human lymphocytes to DEB results in severe GSH depletion and loss of ATP, followed by cell death; (ii) acetyl-L-carnitine elicits a significant protective effect on DEB induced toxicity, which was potentiated by alpha-lipoic acid. Collectively, these findings contribute to increase our knowledge of DEB-induce toxicity and will be very useful when applied in studies with lymphocytes from FA patients, in order to find out a protective agent against spontaneous and DEB-induced chromosome instability.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 7