Phase 2 enzyme induction by conjugated linoleic acid improves lupus-associated oxidative stress.
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.
Bergamo
Paolo
P
Istituto di Scienze dell' Alimentazione, Consiglio Nazionale delle Ricerche (CNR-ISA), via Roma 52, 83100, Avellino, Italy. p.bergamo@isa.cnr.it
Maurano
Francesco
F
Rossi
Mauro
M
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000975:Antioxidants / Q000032:analysis; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D018890:Chemoprevention; D004195:Disease Models, Animal; D004790:Enzyme Induction; D005721:Glutamate-Cysteine Ligase / Q000032:analysis / Q000096:biosynthesis; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000032:analysis / Q000096:biosynthesis; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D016660:NAD(P)H Dehydrogenase (Quinone); D009252:NADPH Dehydrogenase / Q000032:analysis / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects*; D013154:Spleen / Q000201:enzymology
D000974:Antibodies, Antinuclear; D000975:Antioxidants; D001323:Autoantibodies; D015415:Biomarkers; D044243:Linoleic Acids, Conjugated; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; D009252:NADPH Dehydrogenase; D005982:Glutathione Transferase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione