Role of arachidonic acid metabolites in acid-pepsin injury to rabbit esophagus.
The role of cyclooxygenase and lipoxygenase metabolites of arachidonic acid in experimental esophageal were lumenally perfused for 1 h with acidified saline (pH 2.0) with or without pepsin followed by a second hour with acidified saline. Separate groups of pepsin-perfused animals were pretreated with indomethacin, a cyclooxygenase inhibitor, or BW755C, a lipoxygenase-cyclooxygenase inhibitor. Esophageal injury was graded grossly. H+ and hemoglobin fluxes were determined. Acidified saline caused no significant damage. Pepsin induced moderate injury. Indomethacin decreased pepsin-induced H+ flux by 55% without affecting the other indices. BW755C, by all measurements, dramatically increased pepsin-induced injury. In separate experiments, cyclooxygenase activity was decreased by indomethacin and BW755C by 62% and 49%, respectively. Lipoxygenase activity was decreased 74% by BW755C and was not significantly affected by indomethacin. These results suggest that esophageal cytoprotection is mediated by endogenous lipoxygenase metabolites.
Stein
B E
BE
Department of Medicine, New York Medical College, Valhalla.
Schwartzman
M L
ML
Carroll
M A
MA
Stahl
R E
RE
Rosenthal
W S
WS
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001091:Arachidonate Lipoxygenases / Q000502:physiology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000502:physiology*; D004941:Esophagitis / Q000139:chemically induced / Q000473:pathology*; D004947:Esophagus / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000627:therapeutic use*; D008297:Male; D010434:Pepsin A / Q000633:toxicity; D011292:Premedication; D011720:Pyrazoles / Q000627:therapeutic use*; D011817:Rabbits; D012965:Sodium Chloride / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D011720:Pyrazoles; D016718:Arachidonic Acid; D012965:Sodium Chloride; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D001091:Arachidonate Lipoxygenases; D010434:Pepsin A; D007213:Indomethacin