Improvement of genetic stability in lymphocytes from Fanconi anemia patients through the combined effect of alpha-lipoic acid and N-acetylcysteine

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Filipa Ponte (Author) Other; Rosa Sousa (Author) Other; Ana Paula Fernandes (Author) Other; Cristina Goncalves (Author) Other; Jose Barbot (Author) Other; Felix Carvalho (Author) FFUP; Beatriz Porto (Author) ICBAS

Journal

Title: Orphanet Journal of Rare Diseases

Vol. 7

Final page: 28

ISSN: 1750-1172

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 20 Citations

Scopus - 26 Citations

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Authenticus ID: P-002-A0G

DOI: 10.1186/1750-1172-7-28

Abstract (EN): Fanconi Anemia (FA) is a rare genetic disorder, characterized by progressive bone marrow failure and increased predisposition to cancer. Despite being highly heterogeneous, all FA patients are hypersensitive to alkylating agents, in particular to 1,2:3,4-diepoxybutane (DEB), and to oxidative damage. Recent studies point to defective mitochondria in FA cells, which is closely related with increased production of reactive oxygen species (ROS) and concomitant depletion of antioxidant defenses, of which glutathione is a well-known biomarker. The objective of the present work is to evaluate the putative protective effect of a-lipoic acid (alpha-LA), a mitochondrial protective agent, and N-acetylcysteine (NAC), a direct antioxidant and a known precursor for glutathione synthesis, in spontaneous and DEB-induced chromosome instability (CI) in lymphocyte cultures from FA patients. For that purpose, lymphocyte cultures from 15 FA patients and 24 healthy controls were pre-treated with 20 mu M alpha-LA, 500 mu M NAC and alpha-LA plus NAC at the same concentrations, and some of them were exposed to DEB (0.05 mu g/ml). A hundred metaphases per treatment were scored to estimate the relative frequency of spontaneous and DEB-induced chromosome breakage. The obtained results revealed that a cocktail of alpha-LA and NAC can drastically improve the genetic stability in FA lymphocytes in vitro, decreasing CI by 60% and 80% in cultures from FA patients and FA mosaic/chimera patients, respectively. These results suggest that the studied cocktail can be used as a prophylactic approach to delay progressive clinical symptoms in FA patients caused by CI, which can culminate in the delay of the progressive bone marrow failure and early cancer development.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11