We examined the effect of egualen, a stable
azulene derivative, against gastric damage induced by
ischemia/reperfusion (I/R), gastric
bleeding induced by double antiplatelet
therapy with
aspirin (ASA) plus
clopidogrel, and small intestinal damage generated by
loxoprofen, and investigated the possible mechanisms involved in its protective action. Male C57BL/6 mice or SD rats were used under
urethane anesthesia (gastric lesions) or in a conscious (intestinal lesions) state. I/R-induced gastric injury was produced in mice by clamping the celiac artery for 30 min, followed by reperfusion for 60 min. Gastric
bleeding was induced in rats by
luminal perfusion with 25 mM ASA+50 mM HCl for 2 hours in the presence of
clopidogrel (30 mg/kg). To produce small intestinal lesions the rats were given
loxoprofen (60 mg/kg) p.o. and killed 24 hours later. Egualen was given i.d. 60 min before I/R or ASA perfusion, while given p.o. twice 30 min before and 6 hours after
loxoprofen. Egualen significantly prevented the I/R-induced gastric damage, and the effect was equivalent to that of
seratrodast (TXA2 antagonist). This agent also significantly suppressed gastric
bleeding induced by ASA plus
clopidogrel, similar to
PGE2. Likewise, egualen significantly prevented
loxoprofen-induced damage in the small intestine, accompanied by an increase in the secretion of mucus and suppression of bacterial invasion as well as iNOS expression. These results suggest that egualen has a prophylactic effect against various lesions in the gastrointestinal mucosa, probably through its characteristic pharmacological properties, such as TXA2 antagonistic action, local mucosal protection, and stimulation of mucus secretion.