Phase 2 enzyme induction by conjugated linoleic acid improves lupus-associated oxidative stress

Free Radic Biol Med. 2007 Jul 1;43(1):71-9. doi: 10.1016/j.freeradbiomed.2007.03.023. Epub 2007 Apr 12.

Abstract

Conjugated linoleic acid (CLA) exhibits anticancer and anti-inflammatory properties. Its ability to increase total GSH (GSH+GSSG) amount and gamma-glutamylcysteine ligase (gammaGCL) protein expression was recently associated with the inhibition of typical pathological signs in MRL/MpJ-Fas(lpr) mice (MRL/lpr). In the present study the ability of CLA to modulate oxidative stress and phase 2 enzyme activity in the same animal model was investigated. Disease severity was associated with age-dependent production of anti-double-stranded DNA antibodies (anti-dsDNA IgGs) and with enhanced extent of oxidative stress markers: reduced total GSH, increased protein 3-nitrotyrosines (3-NT), and protein-bound carbonyl (PC) amounts. To examine the effect of CLA on antioxidant status, CLA or olive oil (as control) was administered to pregnant MRL/lpr mice. Significantly higher total GSH and Trolox equivalent antioxidant capacity (TEAC) levels were measured in serum of CLA-treated dams (and their pups), as compared with controls. Finally, the antioxidant and chemopreventive properties of CLA were investigated in old MRL/lpr mice. Sera of CLA-treated mice contained higher concentrations of total GSH which were negatively correlated with the levels of oxidative stress markers. Moreover, increased GSH, gammaGCL, glutathione S-transferase (GSTs), and NAD(P)H:quinone oxidoreductase (NQO1) activities were measured in liver and spleen of CLA-treated animals. In conclusion our data indicate that the activation of detoxifying enzymes may be one of the mechanisms whereby dietary CLA down-regulates oxidative stress in MRL/lpr mice.

MeSH terms

  • Animals
  • Antibodies, Antinuclear / blood
  • Antioxidants / analysis
  • Autoantibodies / blood
  • Biomarkers / blood
  • Chemoprevention*
  • Disease Models, Animal
  • Enzyme Induction
  • Glutamate-Cysteine Ligase / analysis
  • Glutamate-Cysteine Ligase / biosynthesis
  • Glutathione / metabolism
  • Glutathione Transferase / analysis
  • Glutathione Transferase / biosynthesis
  • Linoleic Acids, Conjugated / pharmacology*
  • Liver / enzymology
  • Lupus Erythematosus, Systemic / enzymology*
  • Mice
  • Mice, Inbred MRL lpr
  • NAD(P)H Dehydrogenase (Quinone)
  • NADPH Dehydrogenase / analysis
  • NADPH Dehydrogenase / biosynthesis
  • Oxidative Stress / drug effects*
  • Spleen / enzymology

Substances

  • Antibodies, Antinuclear
  • Antioxidants
  • Autoantibodies
  • Biomarkers
  • Linoleic Acids, Conjugated
  • NAD(P)H Dehydrogenase (Quinone)
  • Nqo1 protein, mouse
  • NADPH Dehydrogenase
  • Glutathione Transferase
  • Glutamate-Cysteine Ligase
  • Glutathione