Polaprezinc (N-(3-aminopropionyl)-L-histidinato zinc) ameliorates dextran sulfate sodium-induced colitis in mice.

Abstract

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.

MATERIAL AND 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.

• Authors: Tatsuya Ohkawara, Hiroshi Takeda, Kanji Kato, Kencho Miyashita, Mototsugu Kato, Toshihiko Iwanaga, Masahiro Asaka
• Journal: Scandinavian journal of gastroenterology (Scand J Gastroenterol) Vol. 40 Issue 11 Pg. 1321-7 (Nov 2005) ISSN: 0036-5521 [Print] England
• PMID: 16334442 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Ulcer Agents
• Cytokines
• Heat-Shock Proteins
• Organometallic Compounds
• Zinc Compounds
• polaprezinc
• Carnosine
• Dextran Sulfate
• Peroxidase

Topics

• Analysis of Variance
• Animals
• Anti-Ulcer Agents (pharmacology)
• Biopsy, Needle
• Carnosine (analogs & derivatives, pharmacology)
• Colitis (drug therapy, pathology)
• Cytokines (drug effects, metabolism)
• Dextran Sulfate
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Heat-Shock Proteins (drug effects, metabolism)
• Immunohistochemistry
• Intestinal Mucosa (drug effects, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Organometallic Compounds (pharmacology)
• Peroxidase (drug effects, metabolism)
• Probability
• Random Allocation
• Reference Values
• Sensitivity and Specificity
• Zinc Compounds