Role of leukotrienes in acute gastric lesions induced by ethanol,taurocholate, aspirin,platelet-activating factor and stress in rats

This study was designed to determine the role of leukotriene C₄ (LTC₄) in the formation of acute gastric lesions induced by 100% ethanol, acidified taurocholate (TC), acidified aspirin (ASA), platelet-activating factor (PAF), and water-immersion and restraint stress. Exogenous LTC₄ alone administered in gradually increasing doses (5–20g/kg/hr) caused only mild hemorrhagic lesions in the gastric mucosa but when combined with 100% ethanol, acidified TC, acidified ASA, or stress, it increased significantly the mean lesion area and lesion number as compared to those produced by these ulcerogens alone. FPL 55712, a LTC₄ antagonist, given orally (2.5–10 mg/kg) reduced dose-dependently the extent of gastric lesions in all experimental models used and completely prevented the deleterious effects of exogenous LTC₄ on gastric mucosa. PAF augmented the mucosal lesions induced by 100% ethanol, and this was also reduced by the pretreatment with FPL 55712. FPL 55712-induced gastroprotection against various ulcerogens was reversed, in part, by indomethacin, indicating that it could be attributed not only to the LTC₄ antagonism but also to increased biosynthesis of PGs. This study provides evidence that LTC₄ is involved in the formation of acute gastric damage and the antagonism of LTC₄ may protect the mucosa against various ulcerogens.