Leukotrienes do not contribute to the pathogenesis of indomethacin-induced ulceration of the gastric antrum in the re-fed rat.
The potential involvement of leukotrienes in the pathogenesis of indomethacin-induced ulceration of the rat gastric antrum has been studied. Pretreatment with the leukotriene biosynthesis inhibitor, MK886 (30 mg/kg p.o.), inhibited the increases in blood and antral leukotriene B4 release ex vivo associated with the evolution of antral ulceration. Despite this, however, there was no significant reduction in either the area of antral ulceration, or in the associated blood neutrophilia and neutrophil infiltration into the gastric antrum. Similarly, pretreatment with the leukotriene B4 antagonist, SC41930 (50 mg/kg p.o.) or the peptidyl leukotriene antagonist ICI198,615 (50 mg/kg p.o.) did not inhibit the area of antral ulceration induced by indomethacin. Thus, in contrast to published reports studying fundic ulceration, our results suggest that leukotrienes do not play a major role either in the pathogenesis of indomethacin-induced ulceration of the rat gastric antrum or neutrophil infiltration into the damaged antrum.
Trevethick
M A
MA
Department of Gastrointestinal Pharmacology, Glaxo Group Research Ltd, Ware, Herts, UK.
Clayton
N M
NM
Bahl
A K
AK
Strong
P
P
Harman
I W
IW
D000284:Administration, Oral; D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D007191:Indazoles / Q000008:administration & dosage / Q000494:pharmacology; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007213:Indomethacin / Q000008:administration & dosage / Q000633:toxicity*; D007279:Injections, Subcutaneous; D020024:Leukotriene Antagonists; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors* / Q000097:blood; D008854:Microscopy, Electron; D011706:Pyloric Antrum / Q000187:drug effects* / Q000293:injuries; D051381:Rats; D013189:SRS-A / Q000037:antagonists & inhibitors; D013276:Stomach Ulcer / Q000139:chemically induced*; D002722:Chlorobenzenes
D001578:Benzopyrans; D007191:Indazoles; D007211:Indoles; D007213:Indomethacin; D020024:Leukotriene Antagonists; D007975:Leukotriene B4; D013189:SRS-A; C060893:MK-886; D002722:Chlorobenzenes; C054217:ICI 198615; C059950:SC 41930