Long-lasting cytoprotection after pentadecapeptide BPC 157, ranitidine, sucralfate or cholestyramine application in reflux oesophagitis in rats

Recently, the effectiveness of pentadecapeptide BPC 157 and other anti-ulce r agents, called 'direct cytoprotection', was evidenced in totally gastrect omized rats duodenum challenged with cysteamine 24 h after surgery, and sac rificed 23 h after ulcerogen application. The further focus was on the poss ibility that this effect could be seen over a more prolonged period (1, 2, 4 weeks), and in other parts of the gastrointestinal tract (i.e. oesophagus ). After the removal of the stomach, the oesophagus and jejunum were joined by a termino-lateral anastomosis. The animals were euthanized 7, 14 or 28 d after surgery, when oesophagitis was blindly assessed both macroscopicall y (percentage of ulcerations areas) and microscopically (percentage of area s of ulcers, regeneration and hyperplasia; number of inflammatory cells - p olymorphonuclear and mononuclear). Starting 24 h after surgery, the medicat ion was continuously given in the drinking water, in a volume of 12.5 mL/ra t daily, until euthanasia at the end of the observation period, i.e. 7, 14, 28 d following surgery. Based on previous experiments, the doses of agents were daily calculated per kg b.w. as follows: BPC157 125 mg or 125 ng, cho lestyramine 2.5 mg, ranitidine 125 mg, sucralfate 725 mg, whereas controls received 72.5 mL.kg(-1) water. In support of these initial findings, and co nsidering gastrectomized acid-free rats as an ideal model for long-term cyt oprotective studies as well, pentadecapeptide BPC 157 markedly attenuated t ermino-lateral oesophagojejunal anastomosis-reflux oesophagitis also over a quite prolonged period. This efficacy was only partly shared by other anti -ulcer agents. After I-week-old oesophagitis (microscopical assessment), bu t not after 2 or 4 weeks, less damaged mucosa was noted in rats drinking ra nitidine or sucralfate compared to controls. Similar effectiveness was note d for cholestyramine. The obtained results were supported also by inflammat ory cell assessment. Compared with control values, BPC 157-treated groups c onsistently presented less polymorphonuclears and less mononuclears in all assessed periods. Interestingly, the values obtained in other treated group s showed no difference compared with control values. Thus, despite limitati ons, a generalization supporting a direct importance of a common cytoprotec tive approach, could be clearly provided. A useful, long-lasting cytoprotec tive activity (apparently more prominent in BPC 157 rats, than in reference agents, ranitidine, sucralfate, as well as cholestyramine) may be a likely suitable therapy in otherwise resistant reflux oesophagitis conditions. (C ) 1999 Elsevier Science Ltd. Published by Editions scientifiques et medical es Elsevier SAS.