Selective lipoxygenase inhibitor reduces bile acid-induced gastric mucosal injury.
Leukotriene receptor blockade attenuates topical bile acid-induced gastric mucosal injury, suggesting that peptidyl-leukotrienes may be mediators of this injury. The purpose of this study was to test the hypothesis that a selective 5-lipoxygenase inhibitor protects against bile acid-induced gastric epithelial injury in the rat. Prior to injury with 10 and 20 mM acidified taurocholate (pH 1.2), rat stomachs were pretreated with either vehicle or WY50295K (selective 5-lipoxygenase inhibitor, 20 mg/kg). Injury was assessed by measuring net transmucosal hydrogen ion flux, luminal appearance of DNA, and gross mucosal injury. Topical 5-lipoxygenase inhibitor significantly reduced luminal H+ ion loss, surface epithelial cell loss (as measured by luminal accumulation of DNA), and gross mucosal injury in bile acid-injured stomachs compared to controls. This study lends further support to the hypothesis that leukotrienes may be mediators of bile acid-induced gastric mucosal injury.
Sullivan
T R
TR
Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Cordero
J A
JA
Mercer
D W
DW
Ritchie
W P
WP
Dempsey
D T
DT
D000143:Acids / Q000494:pharmacology; D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D009280:Naphthaleneacetic Acids / Q000494:pharmacology*; D014677:Pharmaceutical Vehicles; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid / Q000494:pharmacology
D000143:Acids; D001647:Bile Acids and Salts; D016859:Lipoxygenase Inhibitors; D009280:Naphthaleneacetic Acids; D014677:Pharmaceutical Vehicles; D011804:Quinolines; C067525:S(alpha)-methyl-6-(2-quinolinylmethoxy)-2-naphthaleneacetic acid; D013656:Taurocholic Acid; D004247:DNA