Ulcerogenic and healing impairing actions of monochloramine in rat stomachs: effects of zinc L-carnosine, polaprezinc.
Effects of a novel zinc compound (polaprezinc), N-(3-aminopropionyl)-L-histidinato zinc, on the mucosal ulcerogenic and healing impairing responses induced by monochloramine (NH2Cl) were examined in rat stomach. Oral administration of NH2Cl (> 60 mM) produced severe hemorrhagic lesions in unanesthetized rat stomachs with a marked increase of thiobarbituric acid reactants (TBAR). Pretreatment of the animals with polaprezinc (3 approximately 30 mg/kg, p.o.) showed a dose-dependent inhibition against gastric ulcerogenic and TBAR responses induced by NH2Cl (120 mM). Likewise, mucosal exposure to NH4OH (60 mM) in urethane anesthetized stomachs made ischemic by bleeding from the carotid artery (1 ml per 100 g body w.t.) resulted in severe gastric lesions. This ulcerogenic response caused NH4OH plus ischemia was also attenuated by prior application of polaprezinc as well as taurine (25 mg/ml, 1 ml). On the other hand, the healing of gastric mucosal lesions induced by NH2Cl occurred more slowly than of ethanol-induced lesions, and the latter was significantly delayed by the repeated administration of NH2Cl. Polaprezinc (> 10 mg/kg, p.o.) given twice daily for 7 days not only accelerated the healing of NH2Cl-induced gastric lesions but also antagonized the delayed healing of ethanol-induced lesions in the presence of NH2Cl as well. Polaprezinc showed a scavenging action against NH2Cl in vitro. These results suggest that NH2Cl caused deleterious action on the healing of pre-existing acute lesions as well as irritating action to the mucosa in the rat stomach. Polaprezinc not only protects the stomach against injury caused by NH2Cl but also promotes healing of NH2Cl-induced gastric lesions as well as the delayed healing of ethanol-induced lesions caused by NH2Cl. Although the detailed mechanisms underlying these actions of polaprezinc remain unknown, they may be partly attributable to a scavenging action of this agent against NH2Cl.
Nishiwaki
H
H
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Japan.
Kato
S
S
Sugamoto
S
S
Umeda
M
M
Morita
H
H
Yoneta
T
T
Takeuchi
K
K
D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D002336:Carnosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002700:Chloramines / Q000008:administration & dosage / Q000494:pharmacology*; D003603:Cytotoxins / Q000494:pharmacology / Q000502:physiology*; D000431:Ethanol; D005753:Gastric Mucosa / Q000187:drug effects; D008297:Male; D009942:Organometallic Compounds / Q000627:therapeutic use*; D051381:Rats; D012997:Solvents; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy*; D014945:Wound Healing / Q000187:drug effects*; D017967:Zinc Compounds
D000897:Anti-Ulcer Agents; D002700:Chloramines; D003603:Cytotoxins; D009942:Organometallic Compounds; D012997:Solvents; D017967:Zinc Compounds; C061957:polaprezinc; D000431:Ethanol; D002336:Carnosine; C030816:chloramine