Leukocyte infiltration, improved levels of
intercellular adhesion molecule 1 (ICAM-1), and oxidative stress in the colon are the principal factors in
inflammatory bowel disease. The goal of the current study was to explore the effects of
adelmidrol, an analog of the anti-inflammatory
fatty acid amide signaling molecule
palmitoylethanolamide, in mice subjected to experimental
colitis. Additionally, to clarify whether the protective action of
adelmidrol is dependent on the activation of
peroxisome proliferator-activated receptors (PPARs), we investigated the effects of a PPARγ antagonist,
GW9662, on
adelmidrol action.
Adelmidrol (10 mg/kg daily, o.s.) was tested in a murine experimental model of
colitis induced by intracolonic administration of
dinitrobenzene sulfonic acid. Nuclear factor-κB translocation,
cyclooxygenase-2, and phosphoextracellular signal-regulated
kinase, as well as
tumor necrosis factor-α and interleukin-1β, were significantly increased in colon tissues after
dinitrobenzene sulfonic acid administration. Immunohistochemical staining for
ICAM-1,
P-selectin,
nitrotyrosine, and
poly(ADP)ribose showed a positive staining in the inflamed colon. Treatment with
adelmidrol decreased
diarrhea,
body weight loss, and
myeloperoxidase activity.
Adelmidrol treatment, moreover, reduced nuclear factor-κB translocation,
cyclooxygenase-2, and phosphoextracellular signal-regulated
kinase expression; proinflammatory
cytokine release; and the incidence of
nitrotyrosine and
poly(ADP)ribose in the colon. It also decreased the upregulation of
ICAM-1 and
P-selectin.
Adelmidrol treatment produced a reduction of Bax and an intensification of Bcl-2 expression. This study clearly demonstrates that
adelmidrol exerts important anti-inflammatory effects that are partly dependent on PPARγ, suggesting that this molecule may represent a new pharmacologic approach for
inflammatory bowel disease treatment.