Effects of trimetazidine on acetic acid-induced colitis in female Swiss rats


Kuralay F., Yildiz C., Ozutemiz O. , Islekel H., Caliskan S., Bingol B., ...More

JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES, vol.66, no.2, pp.169-179, 2003 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 66 Issue: 2
  • Publication Date: 2003
  • Doi Number: 10.1080/15287390306402
  • Title of Journal : JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES
  • Page Numbers: pp.169-179

Abstract

Induction of colitis by acetic acid (AA) in the rat is widely used experimental model of inflammatory bowel disease (IBD) and ulcerations. AA as an irritant induces colitis involving infiltration of colonic mucosa with neutrophils and increased production of inflammatory mediators, such as hydrogen peroxide (H2O2), nitric oxide (NO), myeloperoxiclase activity (MPO), and tumor necrosis factor (TNF-alpha). Trimetazidine (TMZ), an antianginal compound, was administered to investigate if its cytoprotective features in cardiac tissue are also effective in AA colitis where ischemic injury contributes to colitis. Administration of TMZ intraperitoneally improved the macroscopic and microscopic score alterations produced by AA, AA administration significantly elevated colonic MPO activity; however, treatment with TMZ significantly lowered this enzyme activity compared to AA. AA administration significantly enhanced superoxide dismutase (SOD) activities, except for A/A + TMZ given rectally, TMZ treatment significantly, lowered nitrate levels, but AA increased these levels. AA administration markedly lowered TNF-alpha levels, but TMZ treatment elevated these levels to control. These findings indicate that overproduction of NO may be involved in the immunosuppression observed during acute AA-induced rat colitis, In conclusion, TMZ treatment was more effective via the intraperitoneal than rectal route, and may be beneficial in therapy of colitis.