Polaprezinc attenuates the Helicobacter pylori-induced gastric mucosal leucocyte activation in Mongolian gerbils--a study using intravital videomicroscopy.
BACKGROUND
We previously demonstrated that Helicobacter pylori colonization evokes gastric mucosal inflammation and an extensive increase in lipid peroxides and glutathione in Mongolian gerbils. Zinc and its derivative, polaprezinc, have been reported to be potent antioxidants in gastric mucosa.


OBJECTIVE
To examine the effect of polaprezinc on gastric mucosal oxidative inflammation in H. pylori-colonized Mongolian gerbils.


METHODS
Sixty-eight male Mongolian gerbils were orally inoculated with H. pylori (ATCC43504, 5 x 10(8) CFUs/gerbil; H. pylori group) and 35 gerbils were inoculated with the culture media (control group). Twenty-two gerbils in the H. pylori and 13 gerbils in the control group were fed with diets containing polaprezinc (0.06%, 100 mg/kg, 10 times the usual clinical dose) (H. pylori + polaprezinc group, polaprezinc group). The remaining gerbils were fed a standard laboratory chow diet. Neutrophil infiltration, assessed histologically and by the activity of myeloperoxidase, the contents of CXC-chemokine (GRO/CINC-1-like protein) and the contents of thiobarbituric acid-reactive substances, was evaluated in each group 12 weeks after the inoculation. Separately, gastric mucosal leucocyte activation and capillary perfusion were also assessed using intravital microscopy 2, 4, 8 and 12 weeks after the inoculation.


RESULTS
In all H. pylori-inoculated animals, the bacterial infection persisted throughout the experimental period. Gastric mucosal lesion formation in the H. pylori group was significantly inhibited in the H. pylori + polaprezinc group. Elevated levels of myeloperoxidase activity, GRO/CINC-1 and thiobarbituric acid-reactive substances in the H. pylori group at 12 weeks were attenuated significantly by polaprezinc treatment. Enhanced levels of venular leucocyte activation observed in the H. pylori group were attenuated significantly in the H. pylori + polaprezinc group during both the early phase (2 weeks) and late phase (12 weeks).


CONCLUSIONS
Polaprezinc inhibited H. pylori-associated gastric mucosal oxidative inflammation, including initial micro-vascular leucocyte activation, in Mongolian gerbils.
Suzuki
H
H
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Mori
M
M
Seto
K
K
Miyazawa
M
M
Kai
A
A
Suematsu
M
M
Yoneta
T
T
Miura
S
S
Ishii
H
H
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002336:Carnosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000276:immunology* / Q000473:pathology; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000276:immunology* / Q000473:pathology / Q000662:veterinary; D016480:Helicobacter pylori / Q000472:pathogenicity*; D007249:Inflammation; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D009942:Organometallic Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction; D017967:Zinc Compounds
D000897:Anti-Ulcer Agents; D009942:Organometallic Compounds; D017967:Zinc Compounds; C061957:polaprezinc; D002336:Carnosine