Mycophenolate mofetil impairs the integrity of colonic anastomosis.
BACKGROUND
The aim of this experimental study was to investigate the effect of mycophenolate mofetil (MMF) during the three phases of colonic anastomosis healing and specifically to check the effect of MMF on the expression of transforming growth factor-beta1 (TGF-beta1), one of the most important growth factors contributing to mechanical stability of colonic anastomosis.


METHODS
Sixty male Wistar rats underwent colonic resection and end-to-end anastomosis. The animals were divided into two groups, a study group given MMF 40 mg/kg, intraduodenally and a control group given vehicle. The rats were sacrificed at 3, 7, and 14 days (10 animals in each group). The anastomoses were tested by measuring bursting pressure and hydroxyproline content. Histological examination and immunohistochemical expression of TGF-beta1 also were assessed.


RESULTS
The mean bursting pressure in the study group was significantly lower on day 3 and 7, but there was no statistical significance on day 14. The mean hydroxyproline content was lower in the study group on days 3, 7, and 14. Histology showed decreased number of macrophages and fibroblasts on days 3 and 7 but no difference on day 14. The expression of TGF-beta1 was significantly reduced in the study group, with the difference being more pronounced on days 3 and 7.


CONCLUSIONS
MMF weakens the integrity of colonic anastomosis, and this effect is more significant during the inflammatory phase of healing. MMF has a negative effect on macrophages and TGF-beta1 expression, resulting in decreased collagen accumulation at the anastomosis.
Sikas
Nicholas
N
Transplantation Department, Hippokration Hospital, Thessaloniki, Greece. nsikas@hotmail.com
Imvrios
George
G
Takoudas
Dimitrios
D
Gakis
Dimitrios
D
Papanikolaou
Vasilios
V
D000714:Anastomosis, Surgical; D000818:Animals; D003106:Colon / Q000033:anatomy & histology / Q000601:surgery*; D005347:Fibroblasts; D006909:Hydroxyproline / Q000032:analysis; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007249:Inflammation; D008264:Macrophages; D008297:Male; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives*; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D012421:Rupture; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000032:analysis; D053773:Transforming Growth Factor beta1; D014945:Wound Healing / Q000187:drug effects
D007166:Immunosuppressive Agents; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D009173:Mycophenolic Acid; D006909:Hydroxyproline