Polaprezinc, a gastroprotective agent: attenuation of monochloramine-evoked gastric DNA fragmentation.
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.
Suzuki
H
H
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Mori
M
M
Seto
K
K
Nagahashi
S
S
Kawaguchi
C
C
Morita
H
H
Suzuki
M
M
Miura
S
S
Yoneta
T
T
Ishii
H
H
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
D000897:Anti-Ulcer Agents; D002700:Chloramines; D009942:Organometallic Compounds; D017967:Zinc Compounds; C061957:polaprezinc; D013654:Taurine; D019287:Zinc Sulfate; D002336:Carnosine; C030816:chloramine