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


CONCLUSIONS
We conclude that thalidomide influenced collagen maturation. There was a stronger action of metalloproteinases, possibly indicating a negative tendency for the healing process.
Division of Coloproctology, Department of Surgery and Anatomy, Ribeirão Preto Faculty of Medicine, University of São Paulo, SP, Brazil.
Samuel Gama
SG
Veneziano
Leandra Naira Zambelli
LN
Ramalho
Fernando Silva
FS
Ramalho
Antônio Dorival
AD
Campos
José Joaquim Ribeiro da
JJ
Rocha
Omar
O
Feres
D000714:Anastomosis, Surgical; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D003094:Collagen / Q000096:biosynthesis; D003106:Colon / Q000601:surgery*; D004195:Disease Models, Animal; D006909:Hydroxyproline / Q000032:analysis; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013529:Surgical Wound Dehiscence; D013792:Thalidomide / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D014945:Wound Healing / Q000187:drug effects*
D020533:Angiogenesis Inhibitors; D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A; D013792:Thalidomide; D003094:Collagen; D020781:Matrix Metalloproteinase 1; D006909:Hydroxyproline