[Preventive effects of troxipide on a newly developed model of acute gastric mucosal lesion (AGML) induced by ischemia/reperfusion plus ammonia in the rat].
We have developed a unique rat AGML model produced by ischemia/reperfusion plus 0.2% ammonia (I/R.NH3), either treatment which would not induce mucosal injury when used alone. The effects of troxipide and other gastric mucosal defensive drugs were investigated with this I/R.NH3-induced AGML model and other AGML models in rats. The following results were obtained: 1) Like allopurinol, troxipide at 50-200 mg/kg, p.o. dose-dependently prevented I/R.NH3-induced development of AGML and also the ischemia/reperfusion-induced increase of gastric mucosal thiobarbituric acid (TBA)-reactive substances; 2) Troxipide at 10(-6)-10(-4) M, like allopurinol, inhibited concentration-dependently in vitro xanthine oxidase activity in gastric mucosal homogenates; 3) Troxipide at 50-200 mg/kg, p.o. inhibited AGMLs induced by bleeding plus 0.2% ammonia and by 1.0% ammonia alone; and 4) Troxipide and sofalcone were similar in preventing all AGMLs tested and also the increase of mucosal TBA-reactive substances, but somewhat differed from teprenone, cetraxate hydrochloride, azulene plus L-glutamine and sucralfate. These findings suggest that troxipide may inhibit I/R.NH3-induced AGML development by preventing generation of oxygen free radicals and by protecting against mucosal fragility due to reduced energy metabolism from poor blood flow and also against ammonia-induced disruption of the gastric mucosal barrier. Therefore, troxipide may be highly effective for various AGMLs with multifactor involvement.
Momo
K
K
Technical Center of Development, Kyorin Pharmaceutical Co., Ltd, Tokyo, Japan.
Hoshina
K
K
Ishibashi
Y
Y
Saito
T
T
D000208:Acute Disease; D000641:Ammonia; D000818:Animals; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000473:pathology*; D008297:Male; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury; D013276:Stomach Ulcer / Q000473:pathology / Q000517:prevention & control*
D010880:Piperidines; D017382:Reactive Oxygen Species; D000641:Ammonia; C028936:troxipide