Inhibition by 16, 16-dimethyl PGE2 of ethanol-induced gastric mucosal damage and leukotriene B4 and C4 formation

The effects of PGE₂ and its stable analogue, 16, 16 dimethyl PGE₂ (dmPGE₂) were investigated on ethanol-induced gastric mucosal haemorrhagic lesions and leukotriene formation in the rat. Exposure of the rat gastric mucosa to ethanol , produced a concentration-related increase in the mucosal formation of leukotriene B₄ (LTB₄) which was correlated with macroscopically-apparent haemorrhagic damage to the mucosa. Challenge with absolute ethanol likewise enhanced the mucosal formation of LTC₄ whereas the mucosal formation of 6-keto-PGF_1α was unaffected. Challenge of the rat gastric mucosa with ethanol induced a concentration-dependent increase in the formation of LTB₄ and LTC₄, but not 6-keto PGF_1α. Pretreatment with PGE₂ (200–500μg/kg p.o.) prevented the haemorrhagic mucosal damage induced by oral administration of absolute ethanol but not the increased formation of leukotrienes by the mucosa. In contrast, pretreatment with a high dose of dmPGE₂ (20μg/kg p.o.) prevented both the gastric mucosal lesions and the increase mucosal leukotriene formation. The differences in the effects of these prostaglandins may be related to the nature or degree of protection of the gastric mucosa. Thus, high doses of dmPGE₂ but not PGE₂ may protect the cells close the luminal surface of the mucosa and hence reduce the stimulation of leukotriene synthesis by these cells.