ORAL TREFOIL PEPTIDES PROTECT AGAINST ETHANOL-INDUCED AND INDOMETHACIN-INDUCED GASTRIC INJURY IN RATS

Background & Aims: The trefoil factors, a family of proteins abundantl y expressed in gastrointestinal mucous cells, protect the epithelium i n vitro. This study determines the effects of exogenously administered trefoil peptides on experimental injury in rats in vivo, Methods: Gas tric injury was induced by either intragastric absolute ethanol (1.0 m t) or subcutaneous indomethacin (20 mg/kg). Recombinant human spasmoly tic polypeptide (rHSP) or rat intestinal trefoil factor (ITF) were adm inistered at different doses and time points before or after injury. V ehicle or bovine serum albumin was used as control. The pH of the stom ach contents was assessed when the rats were killed, Gastric injury wa s blindly evaluated macroscopically and histologically. Serum levels o f rHSP and ITF were determined by an enzyme-linked immunosorbent assay , Results: Oral rHSP and ITF markedly protected against both ethanol- and indomethacin-induced gastric injury (P < 0.005 at doses of 1-15 mg /rat) when given up to 2 hours before injury; no protection was noted by intraperitoneal rHSP against ethanol injury, Intraperitoneal rHSP p rotected against indomethacin-induced injury only at the maximal dose given (15 mg). Neither rHSP nor ITF altered gastric pH, Protection was not associated with systemic absorption of trefoil peptides, Conclusi ons: Topical trefoil peptides protect the gastric mucosa against ethan ol- and indomethacin-induced gastric injuries. These peptides contribu te to surface mucosal defense.