title: Preferential response of glutathione-related enzymes to folate-dependent changes in the redox state of rat liver.
abstract: BACKGROUND
  Oxidative stress likely constitutes an important contributing factor in the onset of degenerative diseases associated with folate deficiency. Direct, as well as homocysteine-linked, antioxidant properties of folate could explain its preventive effect on these pathologies.
  
  
  OBJECTIVE
  Our study aimed at determining the changes in the redox status of adult rats as a function of folate intake.
  
  
  METHODS
  Adult male rats were pair-fed for 4 weeks with a semi-synthetic diet containing 0, 0.5, 1.5, 8 or 20 mg of folic acid/kg. Folate and homocysteine concentrations, redox status markers and antioxidant enzyme activities were measured in the plasma and/or liver of the rats. A principal component analysis of the overall data was performed to draw a general scheme of the changes observed between the conditions.
  
  
  RESULTS
  Folate deficiency caused increased homocysteinemia and features of oxidative stress including reduced plasma antioxidant capacity together with increased lipid peroxidation in liver and heart. This was associated with an increase in the specific activity of several enzymes involved in liver glutathione metabolism (glutathione peroxidase, glutathione reductase and glutathione S-transferase), suggesting an adaptive tissue response to the oxidative stress induced by folate deficiency. In contrast, no such variation was observed for hepatic superoxide dismutase and catalase.
  
  
  CONCLUSIONS
  Despite no changes in hepatic levels of total glutathione, our findings indicate that glutathione-dependent antioxidant pathways could be particularly involved in the compensatory mechanism committed by liver to counteract the oxidative stress induced by folate deficiency. They also suggest that folate supplementation may not be associated with a better antioxidant protection of rats.
authors.affiliation: Unité de Nutrition Humaine, Institut National de la Recherche Agronomique, Centre de Theix/Clermont-Ferrand, Saint-Genès Champanelle, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Chanson
authors.forename: Edmond
authors.initials: E
authors.lastname: Rock
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Martin
authors.forename: Anne
authors.initials: A
authors.lastname: Liotard
authors.forename: Patrick
authors.initials: P
authors.lastname: Brachet
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005492:Folic Acid / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism; D005494:Folic Acid Deficiency / Q000097:blood / Q000378:metabolism*; D005978:Glutathione / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D005980:Glutathione Reductase / Q000187:drug effects / Q000378:metabolism; D005982:Glutathione Transferase / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D005492:Folic Acid; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione