Mucosal Ulcerogenic Action of Monochloramine in Rat Stomachs (Effects of Polaprezinc and Sucralfate)

Abstract

Effects of a novel zinc compound polaprezinc[N-(3-aminopropionyl)-L-histidinatozinc] and sucralfateon the mucosal ulcerogenic responses induced bymonochloramine (NH₂Cl) were examined in ratstomachs. Oral administration of NH₂Cl (≥60mM) produced severe lesions in unanesthetized ratstomachs, with concomitant increase of lipidperoxidation. These lesions were aggravated by sensorydeafferentation but not affected by pretreatment with indomethacinor L-NAME. The mucosal ulcerogenic response toNH₂Cl was significantly inhibited by oralpretreatment with either dmPGE₂ (10μg/kg), capsaicin (30 mg/kg), or NOR-3 (3 mg/kg), the NO donor. Gastriclesions induced by NH₂Cl were also inhibitedby prior oral administration of polaprezinc (3-30 mg/kg)as well as sucralfate (30 and 100 mg/kg). The protectiveeffect of polaprezinc was not affected by anypretreatments such as indomethacin, L-NAME, or sensorydeafferentation, while that of sucralfate wassignificantly mitigated in the presence of eitherindomethacin or L-NAME. On the other hand, mucosal exposureto NH₂OH (60 mM) caused a marked PD reductionin ex vivo stomachs made ischemic by bleeding from thecarotid artery, followed by severe gastric lesions.These ulcerogenic and PD responses caused by NH OHplus ischemia were also attenuated by prior applicationof polaprezinc, while dmPGE₂ and sucralfateprevented such lesions without affecting the reduced PDresponse. These results suggest that: (1)NH₂Cl generated either exogenously orendogenously damages the gastric mucosa, (2) bothpolaprezinc and sucralfate protect the stomach againstinjury caused by NH₂Cl, and (3) the mechanisms underlying the protectiveaction of sucralfate may be partly mediated by bothendogenous PGs and NO but may be different from those ofpolaprezinc.