Inhibition of lupus-associated oxidative stress by Conjugated Linoleic Acid paralleled by phase 2 enzymes activation.

Cis9, trans11 and trans19, cis12 Conjugated Linoleic acid (CLA) isomers, predominantly present in food from ruminant animals, exhibited anti-carcinogenic and anti-inflammatory properties. Oxidative stress is known to be implicated in autoimmunity and recent evidences supports an antioxidant basis for the anit-inflammatory activity of CLA in Systemic Lupus Erythematosuus (SLE), as evidenced by the association of enhanced expression of gammaglutamylcysteine ligase (gammaGCL) with the amelioration of autoimmune signs in a murine model of human SLE (MRL/lpr mice). As this enzyme belongs to a group of enzymes (phase 2) crucial for the protecting cells against oxidative stress, the aim of the present study was to examine CLA ability to modulate redox status and phase 2 enzymes activity, namely NAD(P)H:quinone oxidoreductase (NQO1), Glutathione S-Transferase (GST) and gammaGCL in MRL/lpr mice. Age-dependent oxidative stress in murine SLE was first confirmed by decreased GSH concentration and enhanced levels of oxidative stress markers (protein carbonyls, nitrosylated proteins and anti-dsDNA) in diseased mice (20-22 wks old) as compared with pre-diseased animals. Next, enhanced GSH concentration was found in serum of diseased MRL/lpr mice adminstered for two weeks with CLA (30 mg/day), as compared with animals receiving olive oil (control), and its negative correlation with oxidative stress markers content demonstrated the beneficial effects of CLA on animal redox status. Finally phase 2 enzyme involvement was indicated by the enhanced NQO1, GST and gammaGCL activities in spleen and liver of CLA-treated animals as compared with controls. Present results provide thefirst evidence of CLA Ability to activate phase 2 enzymes and to decrease SLE-associated oxidative stress.