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

Scand J Gastroenterol. 2005 Nov;40(11):1321-7. doi: 10.1080/00365520510023530.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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