MUCOSAL ULCEROGENIC ACTION OF MONOCHLORAMINE IN RAT STOMACHS - EFFECTS OF POLAPREZINE AND SUCRALFATE

Effects of a novel zinc compound polaprezinc [N-(3-aminopropionyl)-L-h istidinatozinc] and sucralfate on the mucosal ulcerogenic responses in duced by monochloramine (NH2Cl) were examined in rat stomachs. Oral ad ministration of NH2Cl (>60 mM) produced severe lesions in unanesthetiz ed rat stomachs, with concomitant increase of lipid peroxidation. Thes e lesions were aggravated by sensory deafferentation but not affected by pretreatment with indomethacin or L-NAME. The mucosal ulcerogenic r esponse to NH2Cl was significantly inhibited by oral pretreatment with either dmPGE(2) (10 mu g/kg), capsaicin (30 mg/kg), or NOR-3 (3 mg/kg ), the NO donor. Gastric lesions induced by NH2Cl were also inhibited by prior oral administration of polaprezinc (3-30 mg/kg) as well as su cralfate (30 and 100 mg/kg). The protective effect of polaprezinc was not affected by any pretreatments such as indomethacin, L-NAME, or sen sory deafferentation, while that of sucralfate was significantly mitig ated in the presence of either indomethacin or L-NAME. On the ether ha nd, mucosal exposure to NH4OH (60 mM) caused a marked PD reduction in ex vivo stomachs made ischemic by bleeding from the carotid artery, fo llowed by severe gastric lesions. These ulcerogenic and PD responses c aused by NH4OH plus ischemia were also attenuated by prior application of polaprezinc, while dmPGE(2) and sucralfate prevented such lesions without affecting the reduced PD response. These results suggest that: (1) NH2Cl generated either exogenously or endogenously damages the ga stric mucosa, (2) both polaprezine and sucralfate protect the stomach against injury caused by NH2Cl, and (3) the mechanisms underlying the protective action of sucralfate may be partly mediated by both endogen ous PGs and NO but may be different from those of polaprezinc.