Document Detail

N-acetylcysteine partially reverses oxidative stress and apoptosis exacerbated by Mg-deficiency culturing conditions in primary cultures of rat and human hepatocytes.
MedLine Citation:
PMID:  17031004     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: The effects of magnesium (Mg) deficiency on the rate of oxidative stress and apoptosis in primary cultures of human hepatocytes were compared to cultured rat hepatocytes. The possible reversion by N-acetylcysteine (NAC) in Mg-deficient culturing conditions was evaluated. METHODS: Incubations were conducted for up to 72 h in media containing a deficient (0-0.4 mM) or a physiological (0.8 mM) Mg concentration, and in the presence or absence of NAC after 24 h of culture in these Mg concentration conditions. RESULTS: We obtained similar profiles in terms of apoptosis and oxidative stress in primary cultures of human hepatocytes, as compared to rat hepatocytes, i.e. a Mg concentration-dependent effect on the caspase-3 activity and GSH levels after 72 h of culture, caspase-3 activity being highest and GSH levels being lowest in Mg-free cultures. The addition of NAC to culture media after the first 24 h of culture increased GSH concentrations. This was accompanied in Mg-deficient cultures by a decrease in both the caspase-3 activity and the lipid peroxidation. However, when culturing hepatocytes with physiological Mg concentrations, an increase in both caspase-3 activity and lipid peroxidation was observed. CONCLUSIONS: Our results indicate that Mg deficiency exacerbates the rate of apoptosis in cultured hepatocytes, associated with an increase in oxidative stress, the sensitivity of human hepatocytes being equivalent to that of rat hepatocytes. They also indicate a dual role of NAC and/or GSH, i.e. protective for hepatocytes placed in a Mg-deficient environment, while deleterious for hepatocytes placed in a Mg-physiological environment.
Hélène Martin; Catherine Abadie; Bruno Heyd; Georges Mantion; Lysiane Richert; Alain Berthelot
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of the American College of Nutrition     Volume:  25     ISSN:  0731-5724     ISO Abbreviation:  J Am Coll Nutr     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-10-10     Completed Date:  2007-01-09     Revised Date:  2008-06-23    
Medline Journal Info:
Nlm Unique ID:  8215879     Medline TA:  J Am Coll Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  363-9     Citation Subset:  IM    
Laboratoire de Biologie Cellulaire, EA 3921, UFR des Sciences Médicales et Pharmaceutiques, Place Saint-Jacques, 25030 Besançon cedex, France.
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MeSH Terms
Acetylcysteine / pharmacology*
Apoptosis / drug effects*
Caspase 3 / metabolism
Cells, Cultured
Dose-Response Relationship, Drug
Free Radical Scavengers / pharmacology
Glutathione / metabolism
Hepatocytes / cytology,  physiology*
Lipid Peroxidation / drug effects
Magnesium / metabolism,  pharmacology*
Magnesium Deficiency / physiopathology*
Oxidative Stress / drug effects*
Reg. No./Substance:
0/Free Radical Scavengers; 616-91-1/Acetylcysteine; 70-18-8/Glutathione; 7439-95-4/Magnesium; EC 3.4.22.-/Caspase 3

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