Effect of thalidomide on the healing of colonic anastomosis, in rats

Acta Cir Bras. 2008:23 Suppl 1:17-23; discussion 23. doi: 10.1590/s0102-86502008000700004.

Abstract

Purpose: Thalidomide, because of its anti-inflammatory properties, as re-emerged as an option for the treatment of Crohn's disease refractory to standard therapy. We studied the effect of thalidomide on the healing of colonic anastomosis.

Methods: Sixty male rats (Rattus norvegicus), were divided into 3 groups of 20 animals each, respectively receiving 0.5 or 1.0 mg/kg thalidomide by the oral route for 7 days, or saline solution (control). All animals were submitted to continuous end-to-end anastomosis with 6-0 Prolene sutures. After sacrifice the anastomoses were analyzed macroscopically and submitted to determination of hydroxyproline, to histology and to immunohistochemistry for metalloproteinase 1, metalloproteinase 1 inhibitor and vascular endothelial growth factor (VEGF).

Results: Statistical analysis of the data showed no significant difference in macroscopic aspect or hydroxyproline determination (p= 0.5403). In the immunohistochemical analysis, the following p values were obtained: p = 0.5817 for VEGF, p = 0.1854 for metalloproteinase 1, and p = 0.0023 for metalloproteinase 1 inhibitor, with this last value being considered statistically significant.

Conclusion: We conclude that thalidomide influenced collagen maturation. There was a stronger action of metalloproteinases, possibly indicating a negative tendency for the healing process.

MeSH terms

  • Anastomosis, Surgical
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Biomarkers / analysis
  • Collagen / biosynthesis
  • Colon / surgery*
  • Disease Models, Animal
  • Hydroxyproline / analysis
  • Male
  • Matrix Metalloproteinase 1 / analysis
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Surgical Wound Dehiscence
  • Thalidomide / pharmacology*
  • Vascular Endothelial Growth Factor A / analysis
  • Wound Healing / drug effects*

Substances

  • Angiogenesis Inhibitors
  • Biomarkers
  • Vascular Endothelial Growth Factor A
  • Thalidomide
  • Collagen
  • Matrix Metalloproteinase 1
  • Hydroxyproline