[Effect of FOY-305 on post-operative reflux esophagitis in rats (II). Analysis of mechanism in the pathogenesis of reflux esophagitis after total gastrectomy in rats].
Esophagitis after total gastrectomy has been associated with biliary and pancreatic reflux into the esophagus. The purpose of this study is to clarify the effect of FOY-305 on these factors in the esophagitis. We initially produced esophagitis in rats with total gastrectomy followed by an end-to-side esophago-jejunostomy (Billroth-II). After treatment of FOY-305 on post-operative day 7 in this model, esophageal washout samples were analyzed for increases in activity of trypsin and total bile acid concentration. FOY-305 completely inhibited increases of trypsin activity in 2 and 4 hr, and it significantly (P less than 0.05) reduced bile acid concentration in 4 hr after initiating treatment. In addition, we evaluated the injurious effect of trypsin and sodium taurocholate (Tc-Na) on isolated esophagus of rats by measuring released tyrosine in the medium and used it as an index of the degree of injury. Tc-Na (3-fold of enteral bile acid concentration) inflicted only a slight injurious effect with negligible tyrosine release increases, and it did not show synergistic action when concomitantly used with trypsin. However, trypsin clearly induced increased tyrosine release from the esophageal mucosa, and this effect was significantly (P less than 0.001) inhibited by FOY-305 (50 microM). These results indicate that trypsin is one of the important factors in the pathogenesis of reflux esophagitis after total gastrectomy, and FOY-305 exerts a therapeutic effect by eliciting an inhibitory action against trypsin activity.
Kamiyasu
K
K
Minase Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
Inoshiri
S
S
Omawari
N
N
Okegawa
T
T
Kawasaki
A
A
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D003864:Depression, Chemical; D004942:Esophagitis, Peptic / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism; D004952:Esters; D016670:Gabexate / Q000031:analogs & derivatives*; D005743:Gastrectomy / Q000009:adverse effects*; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014357:Trypsin / Q000378:metabolism* / Q000494:pharmacology; D014361:Trypsin Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D014443:Tyrosine / Q000378:metabolism
D001647:Bile Acids and Salts; D004952:Esters; D006146:Guanidines; D014361:Trypsin Inhibitors; C034532:camostat; D014443:Tyrosine; D016670:Gabexate; D014357:Trypsin