title: Polaprezinc, a gastroprotective agent: attenuation of monochloramine-evoked gastric DNA fragmentation.
abstract: We previously reported that NH2Cl induced extensive DNA fragmentation in gastric cells. Polaprezinc, a zinc-carnosine chelate compound, is reported to be a potent antioxidant in gastric mucosa. The present study was designed to examine whether polaprezinc could attenuate the NH3Cl-induced DNA damage. Gastric cell lines, MKN45, were exposed to NH2Cl in Ca(2+)-containing Hanks' balanced salt solution. DNA fragmentation was evaluated by photometric enzyme immunoassay for in vitro determination of cytoplasmic mono- and oligonucleosomes. Polaprezinc, L-carnosine, and zinc sulfate (ZnSO4) were added to the cell incubation medium to evaluate the inhibitory effect on the formation of cytoplasmic mono- and oligonucleosomes. Separately, the bleaching level of beta-carotene with the addition of each test solution was evaluated to confirm the inhibitory effect against hypochlorous acid. Polaprezinc or L-carnosine, but not ZnSO4, at a concentration of 0.001 mM, significantly attenuated the increased levels of cytoplasmic mono- and oligonucleosomes evoked by 0.001 mM NH2Cl. Polaprezinc and L-carnosine, but not ZnSO4, also inhibited NH2Cl-induced beta-carotene bleaching in the cell-free system. In conclusion, polaprezinc, especially its subportion L-carnosine, inhibited NH2Cl-evoked gastric epithelial DNA fragmentation, suggesting a role for this agent in preventing the progression of gastric epithelial injury induced by NH2Cl.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.forename: K
authors.initials: K
authors.lastname: Seto
authors.forename: S
authors.initials: S
authors.lastname: Nagahashi
authors.forename: C
authors.initials: C
authors.lastname: Kawaguchi
authors.forename: H
authors.initials: H
authors.lastname: Morita
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: S
authors.initials: S
authors.lastname: Miura
authors.forename: T
authors.initials: T
authors.lastname: Yoneta
authors.forename: H
authors.initials: H
authors.lastname: Ishii
mesh_terms: D000704:Analysis of Variance; D000897:Anti-Ulcer Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002336:Carnosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D002700:Chloramines; D004249:DNA Damage; D053938:DNA Fragmentation / Q000187:drug effects*; D005753:Gastric Mucosa / Q000187:drug effects*; D016481:Helicobacter Infections / Q000188:drug therapy; D016480:Helicobacter pylori; D006801:Humans; D009942:Organometallic Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D013654:Taurine / Q000494:pharmacology; D017967:Zinc Compounds; D019287:Zinc Sulfate / Q000494:pharmacology
chemical_list: D000897:Anti-Ulcer Agents; D002700:Chloramines; D009942:Organometallic Compounds; D017967:Zinc Compounds; C061957:polaprezinc; D013654:Taurine; D019287:Zinc Sulfate; D002336:Carnosine; C030816:chloramine