The effect of heparin on trinitrobenzene sulphonic acid-induced colitis in the rat

Aliment Pharmacol Ther. 1998 Mar;12(3):229-36. doi: 10.1046/j.1365-2036.1998.00293.x.

Abstract

Background: Reduced blood coagulability seems to protect against inflammatory bowel disease; pilot studies using heparin in patients with inflammatory bowel disease have reported positive results.

Aim: To evaluate the effects of heparin treatment on microangiographic and on inflammatory parameters in experimental colitis, induced by trinitrobenzene sulphonic acid (TNBS)-ethanol.

Methods: Four groups of rats: (i) controls (saline enema), TNBS-induced colitis with (ii) sham treatment (saline, s.c.), (iii) dexamethasone (0.25 mg/kg/day s.c.) and (iv) heparin (500 U/kg t.d.s., s.c.). Microangiography was performed 2 and 4 days after colitis induction. Partial thromboplastin time, colonic wet weight, macroscopic damage score and mucosal myeloperoxidase (MPO) activity were determined at day 4.

Results: TNBS-induced colitis caused a reduction in visible bowel wall vessels, which was prevented by heparin (P < 0.05) but not by steroids. The macroscopic damage scores and colon wet weights were similar in all colitis groups. Compared to untreated colitis the MPO activity in heparin-treated animals was of borderline significance.

Conclusions: Heparin treatment improved microangiographic features and reduced inflammation to a certain degree. Steroids delayed development of colon hypoperfusion, but were ineffective on MPO activity. It remains to be determined if the observed effects are due to the antithrombotic activity of heparin or to an anti-inflammatory action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / therapeutic use
  • Anticoagulants / administration & dosage
  • Anticoagulants / therapeutic use*
  • Blood Platelets / drug effects
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colon / drug effects
  • Colon / enzymology
  • Colon / pathology
  • Dexamethasone / administration & dosage
  • Dexamethasone / therapeutic use
  • Erythrocyte Count / drug effects
  • Heparin / administration & dosage
  • Heparin / therapeutic use*
  • Male
  • Microradiography
  • Partial Thromboplastin Time
  • Peroxidase / drug effects
  • Peroxidase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Treatment Outcome
  • Trinitrobenzenesulfonic Acid

Substances

  • Anti-Inflammatory Agents
  • Anticoagulants
  • Dexamethasone
  • Trinitrobenzenesulfonic Acid
  • Heparin
  • Peroxidase