Prostaglandin protection of rat colonic mucosa from damage induced by ethanol

The effects of pretreatment with 16,16-dimethyl prostaglandin E₂ (dmPGE₂) on ethanol-induced colonic damage were studied in the rat. Colonic damage was assessed macroscopically, histologically, and using cytoplasmic (lactate dehydrogenase) and lysosomal (acid phosphatase) enzyme markers of cell disruption. Intrarectal administration of 30% ethanol produced grossly visible regions of hyperemia and hemorrhage. Histologically, the ethanol injury was characterized by complete destruction of the surface epithelium and necrosis extending throughout most of the mucosal layer. When incubatedin vitro after challenge with ethanolin vivo, the colons released significantly more acid phosphatase and lactate dehydrogenase than did controls. Intrarectal pretreatment with dmPGE₂ caused a dose-dependent reduction in ethanol-induced damage, as measured by all three parameters. A significant (P<0.05) reduction of macroscopically visible damage was observed with 0.2 g/kg dmPGE₂, while at higher doses (20 g/kg) the histological signs of damage, including that to the colonic epithelium, were reduced or completely prevented. This dose of dmPGE₂ also reduced (P<0.01) the release of the enzymemarkers to control levels. The possibility that this protection was mediated by increased colonic fluid secretion was studied. Pretreatment with dmPGE₂ had no effect on net colonic fluid secretion (measured using the nonabsorbable marker [³H]inulin) or on the absorption of ethanol by the colon. This study demonstrates that intrarectal administration of dmPGE₂ can protect the colonic mucosa from damage induced by direct application of a potent topical irritant. With the highest dose of dmPGE₂ tested (20 g/kg), protection of the colonic epithelium from ethanol injury was observed.