title: Analysis of the effects of iron and vitamin C co-supplementation on oxidative damage, antioxidant response and inflammation in THP-1 macrophages.
abstract: OBJECTIVE
  The aims of the study were to test the susceptibility of THP-1 macrophages to develop oxidative stress and to deploy antioxidant defense mechanisms that insure the balance between the pro- and antioxidant molecules.
  
  
  METHODS
  Differentiated THP-1 were incubated in the presence or absence of iron-ascorbate (Fe/As) (100/1000μM) and the antioxidants Trolox, BHT, α-Tocopherol and NAC.
  
  
  RESULTS
  Fe/As promoted the production of lipid peroxidation as reflected by the formation of malondialdehyde and H(2)O(2) along with reduced PUFA levels and elevated glutathione disulfide/total glutathione ratio, a reliable index of cellular redox status. THP-1 macrophages developed an increase in cytoplasmic SOD activity due in part to high cytoplasmic SOD1. On the other hand, a decline was noted in mRNA and protein of extra-cellular SOD3, as well as the activity of GSH-peroxidase, GSH-transferase and ATOX-1 expression.
  
  
  CONCLUSIONS
  Macrophages activated under conditions of oxidative stress do not adequately deploy a powerful endogenous antioxidant response, a situation that can lead to an enhanced inflammatory response.
authors.affiliation: Research Centre, CHU-Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Marcil
authors.forename: J C
authors.initials: JC
authors.lastname: Lavoie
authors.forename: L
authors.initials: L
authors.lastname: Emonnot
authors.forename: E
authors.initials: E
authors.lastname: Seidman
authors.forename: E
authors.initials: E
authors.lastname: Levy
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002460:Cell Line; D019587:Dietary Supplements; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007249:Inflammation / Q000473:pathology*; D007501:Iron / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D008315:Malondialdehyde / Q000378:metabolism; D008954:Models, Biological; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005227:Fatty Acids; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D007501:Iron; D001205:Ascorbic Acid; D019803:Glutathione Disulfide