Abstract
Abstract AIM To investigate the mucosal protective effect and the mechanisms of action of the anti-ulcer drug oleo-gum-resin in gastric injury induced by indomethacin in rats. METHODS Gastric mucosal injury was induced in male Wistar rats by oral administration of indomethacin at a dose of 60 mg/kg. One hour before indomethacin treatment, animals were orally pretreated with oleo-gum-resin at doses of 125 mg/kg, 250 mg/kg or 500 mg/kg. Four hours after indomethacin administration, the animals were sacrificed and their stomachs were rapidly removed and processed for the evaluation of gastric mucosal damage and the determination of the concentrations of TNF-α, IL-1β, IL-6, NO, PGE2 and myeloperoxidase (MPO) in mucosal tissues. RESULTS Linear hemorrhagic mucosal lesions were observed primarily in the glandular stomach 4 h after oral administration of indomethacin. Pretreatment with oleo-gum-resin markedly reduced the number and severity of gastric lesions in a dose dependent manner. The mucosal concentrations of TNF-α, IL-1β, IL-8, NO, and MPO, which indicates the degree of mucosal infiltration by neutrophils, increased concomitantly with the occurrence of gastric injury in the indomethacin administered rats while PGE2 levels inhibited in this group. Pretreatment with oleo-gum-resin significantly decreased the levels of these inflammatory factors in gastric tissue elicited by indomethacin and enhanced the PGE2 levels. CONCLUSION The mucosal protective effects afforded by oleo-gum-resin on gastric injury induced by indomethacin are mediated by inhibition of mucosal proinflammatory cytokine production and neutrophil infiltration, leading to suppression of mucosal inflammation and subsequent tissue destruction.