5‐HT2 Blockade Protects Against Gastric Ischaemia‐reperfusion Injury in Rats. Role of Oxygen Free Radicals and Lipid Peroxidation

Abstract

Lipid peroxidation and active oxygen metabolites have been suggested to play an important role in the pathogenesis of acute gastric mucosal injury induced by ischaemia-reperfusion. On the-other hand 5-hydroxytryptamine (5-HT) has been shown to contribute to gastric mucosal damage. This ulcerogenic action is likely to be mediated through a depressive action on gastric-mucosal flow via 5-HT blockade and 5-HT2-receptor activation. The aim of this study was to examine the effects of ketanserin a specific 5-HT2 antagonist on gastric injury induced by ischaemia-reperfusion. The peroxidation of lipids and changes in the activities of related enzymes such as gluthatione peroxidase and myeloperoxidase, as a marker of neutrophil infiltration, were also studied. Intraperitoneal administration of ketanserin prevented post-ischaemic mucosal injury. The mean ulcer indexes of rats treated with 2.5, 5 and 10 mg kg−1 were significantly lower than that of control rats. These protective effects were specifically related to a reduction of neutrophil infiltration. Lipid peroxidation in the stomach was increased by ischaemia-reperfusion injury and this increase was inhibited by the administration of all the tested doses of ketanserin. In addition, treatment with ketanserin could improve the decreased gluthatione peroxidase activity. These results suggest that selective blockade of 5-HT2 receptors by ketanserin may be effective on ischaemia-reperfusion gastric injury. The inhibitory effects of ketanserin on neutrophil function and lipid-peroxidation and the increase of glutathione peroxidase activity seem to contribute significantly to the gastroprotection afforded by ketanserin in this experimental model.