Ultramicronized palmitoylethanolamide reduces inflammation an a Th1-mediated model of colitis

Abstract

Inflammatory bowel diseases are idiopathic relapsing disorders characterized by chronic inflammation of the intestinal tract. The aim of the present study was to examine the effect of ultramicronized palmitoylethanolamide (PEAultra), underlining its correlation with PPARα and TLR4; in particular, we aimed at evaluating its anti-inflammatory effect in mice subjected to experimental colitis. Colitis was induced in mice by intracolonic instillation of dinitrobenzene sulfonic acid (DNBS), PEAultra was administered daily intraperitoneally (10 mg/kg) for 4 days. On day 4, animals were sacrificed and tissues were taken for histological and biochemical analysis. Four days after DNBS administration, TNF-α and IL-1β productions were increased in association with colon damage. Neutrophil infiltration, evaluated by MPO activity, in the mucosa was associated with upregulation of ICAM-1 and P-selectin. Immunohistochemistry for nitrotyrosine and PARP showed an intense staining in the inflamed colon. Treatment with PEAultra significantly reduced the appearance of colon damage and the loss of body weight. These effects were associated with a remarkable amelioration in the disruption of the colonic architecture and reduction in colonic MPO activity. PEAultra also reduced the pro-inflammatory cytokine release, the appearance of nitrotyrosine and PARP immunoreactivity as well as the upregulation of ICAM-1 and P-selectin; moreover, pro-MMP-9 and MMP-2 expressions were significantly inhibited in the colon of DNBS-treated mice. Furthermore, we studied PEAultra correlation with PPARα and TLR4, demonstrating that PEAultra inhibited TLR4 pathway through a PPARα independent pathway. Taken together, our results clearly show that this new formulation of PEA may be considered as a possible therapeutic approach against Th1-induced colitis.