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

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Filipa Ponte (Author) Other; Felix Carvalho (Author) FFUP; Beatriz Porto (Author) ICBAS

Journal

Title: Toxicology

Vol. 289

Pages: 52-58

ISSN: 0300-483X

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 13 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7