Irritant action of monochloramine in rat stomachs: effects of zinc L-carnosine (polaprezinc).
1. Effects of a novel zinc compound (polaprezinc), N-(3-aminopropionyl)-L-histidinato zinc, on the mucosal ulcerogenic response induced by ammonia (NH4OH) and monochloramine (NH2Cl) were examined in rat stomachs. 2. Oral administration (1 ml) of NH4OH (> 600 mM) and NH2Cl (> 60 mM) produced severe hemorrhagic lesions in unanesthetized rat stomachs, whereas hypochlorous acid (HClO) even at 120 mM did not cause any macroscopic damage. 3. Pretreatment of the animals with polaprezinc (2-12 mg/ml, 1 ml, PO) showed a dose-dependent inhibition against gastric lesions induced by NH4OH (1,800 nM) or NH2Cl (120mM), and this effect was significant at > 6 mg/ml in either case. These lesions were also significantly prevented by prior administration of dmPGE2 (2 micrograms/ml, 1 ml, PO). 4. Mucosal application of NH4OH (300 mM) and NH2Cl (10 mM) caused a marked reduction of transmucosal potential difference (PD) in ex vivo stomachs of anesthetized rats. The reduced PD responses caused by NH4OH and NH2Cl were prevented dose dependently by preexposure of the mucosa to polaprezinc, but not affected by dmPGE2. 5. Mucosal exposure to NH4OH (60 mM) caused a marked PD reduction in ex vivo stomachs made ischemic by bleeding from the carotid artery (1 ml per 100 g body wt), followed by severe gastric lesions. These ulcerogenic and PD responses caused by NH4OH plus ischemia were attenuated by prior application of polaprezinc as well as taurine (25 mg/ml, 1 ml), while dmPGE2 prevented the lesions without affecting the reduced PD response. 6. These results suggest that (a) NH2Cl damages the gastric mucosa at much lower concentrations than NH4OH, (b) polaprezinc protects the stomach against injury caused by either NH2Cl or NH4OH, and (c) the mechanisms underlying the protective action of polaprezinc remain unclear but may be different from those of dmPGE2.
Nishiwaki
H
H
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Japan.
Kato
S
S
Takeuchi
K
K
D000643:Ammonium Chloride; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002336:Carnosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002700:Chloramines; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009942:Organometallic Compounds / Q000494:pharmacology*; D010438:Peptic Ulcer Hemorrhage / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D017967:Zinc Compounds
D000897:Anti-Ulcer Agents; D002700:Chloramines; D009942:Organometallic Compounds; D017967:Zinc Compounds; D000643:Ammonium Chloride; C061957:polaprezinc; D002336:Carnosine; C030816:chloramine