Leukotriene C4 and D4 are putative mediators of the severe gastric mucosal injury caused by a variety of topical irritants. The purpose of this present study was (1) to investigate the effect of pretreatment with topical leukotriene C4 and D4 on the more superficial injury caused by low concentrations of bile acid and (2) to determine the effect of leukotriene receptor blockade, alone and during leukotriene pretreatment, on this injury. Prior to injury with topical 5 mM acidified taurocholate (pH 1.2) rat stomachs were pretreated with either normal saline, leukotriene C4 or D4, SKF-104353 (a leukotriene receptor antagonist), SKF-104353/LTC4, or SKF-104353/LTD4. Injury was assessed by measuring hydrogen ion flux and DNA efflux, a marker of gastric mucosal cell exfoliation. Both LTC4 and LTD4 significantly increased bile acid-induced luminal hydrogen ion loss and DNA efflux. Leukotriene receptor blockade not only blocked this effect, but also significantly decreased the injury from bile acid alone. Thus, both LTC4 and LTD4 exacerbate the superficial gastric mucosal injury caused by physiologic concentrations of bile acids. Leukotriene receptor blockade with SKF-104353 completely blocks these effects and reduces injury from bile acid alone.
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