Polaprezinc (N-(3-aminopropionyl)-L-histidinato zinc) ameliorates dextran sulfate sodium-induced colitis in mice.
OBJECTIVE
Polaprezinc (N-(3-Aminopropionyl)-L-histidinato zinc), an anti-ulcer drug, has been reported to have an anti-inflammatory action in several inflammatory diseases. The aim of this study was to investigate the effect of polaprezinc on dextran sulfate (DSS)-induced colitis in mice.


METHODS
Mice with colitis induced by DSS were intrarectally treated with polaprezinc (15 mg/kg) or zinc sulfate (7.5 mg/kg) every day after the administration of DSS for 7 days. Disease activity index (DAI) and histological tissue damage were assessed. Levels of myeloperoxidase (MPO) activity, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma in the colon were measured. Expression of heat shock protein (HSP) 25 and HSP70 in the colon was analyzed by Western blot analysis.


RESULTS
DAI and histological scores were remarkably reduced in polaprezinc-treated mice with DSS-induced colitis. Polaprezinc suppressed the increase of MPO activity and the production of TNF-alpha and IFN-gamma in the colon tissues of mice with DSS-induced colitis. Expression of HSP25 and HSP70 was remarkably up-regulated in the colon tissues of polaprezinc-treated mice during DSS treatment.


CONCLUSIONS
Polaprezinc suppresses DSS-induced colitis in mice, partly through inhibition of production of pro-inflammatory cytokine, suppression of neutrophils accumulation and cytoprotection by overexpression of HSPs. Polaprezinc could be useful in the treatment of inflammatory bowel diseases.
Ohkawara
Tatsuya
T
Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. tokawara@med.hokudai.ac.jp
Takeda
Hiroshi
H
Kato
Kanji
K
Miyashita
Kencho
K
Kato
Mototsugu
M
Iwanaga
Toshihiko
T
Asaka
Masahiro
M
D000704:Analysis of Variance; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001707:Biopsy, Needle; D002336:Carnosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003092:Colitis / Q000188:drug therapy* / Q000473:pathology*; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds / Q000494:pharmacology*; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D017967:Zinc Compounds
D000897:Anti-Ulcer Agents; D016207:Cytokines; D006360:Heat-Shock Proteins; D009942:Organometallic Compounds; D017967:Zinc Compounds; C061957:polaprezinc; D002336:Carnosine; D016264:Dextran Sulfate; D009195:Peroxidase