Protective effect of Rumenic acid rich cow's milk against colitis is associated with the activation of Nrf2 pathway in a murine model.

ABSTRACT

Dietary supplementation with pure cis9, trans11 isomer of Conjugated Linoleic Acid -known as Rumenic Acid (RA)- improves cytoprotective defenses downstream through the activation of nuclear factor-E2-related factor-2(Nrf2). This capability, when Rumenic Acid is consumed in the form of foods, is still unknown. The ability of standard (St) or cow milk naturally-enriched in RA (En) to activate Nrf2 pathway and its impact on dextran sodium sulfate (DSS)-induced colitis was comparatively evaluated. Activity of Nrf2 pathway was investigated in colonic tissue of BALB/c mice, receiving 4-week supplement with skimmed milk (SK), St or St reinforced with pure RA (RSt) providing increasing RA dose (0, 124 or 404mg RA/kg-1 b.w, respectively). Next, the anti-oxidant/ anti-inflammatory effect produced by St or En treatment (383mg RA/kg-1 b.w.) was explored. Finally, macroscopic and histomorphologic features of colitis were evaluated in animals challenged with 5% (w/v) DSS, at the end of St or En treatment. Significant activation of Nrf2 pathway is associated with RSt and En intake (P<0.05), but not with SK or En treatment. En pre-treatment offers better protection, in comparison with St, against pro-oxidant, pro-inflammatory signs (P<0.01) and macroscopic signs triggered by DSS. It can be concluded that Nrf2 activation by higher RA amount contained in En is, at least in part, responsible for the improved protection associated with En intake against DSS-induced colitis.