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Transplant Direct. 2016 May 20;2(6):e80. doi: 10.1097/TXD.0000000000000591. eCollection 2016 Jun.

The Effect of Mycophenolate Mofetil on Early Wound Healing in a Rodent Model.

Transplantation direct

Martine Cm Willems, Thijs Hendriks, Roger Mlm Lomme, Ben M de Man, J Adam van der Vliet

Affiliations

  1. Division of Vascular and Transplantation Surgery, Department of Surgery, Radboud University Medical Centre, Nijmegen, The Netherlands.

PMID: 27500270 PMCID: PMC4946522 DOI: 10.1097/TXD.0000000000000591

Abstract

BACKGROUND: Immunosuppressant agents are inevitable for solid organ recipients, but may have a negative effect on wound healing that is difficult to measure because of clinical use of a polydrug regime. The evidence on mycophenolate mofetil (MMF) is scarce and contradictory. This study aims to investigate the effect of MMF administration on wound healing.

METHODS: Ninety-six male Wistar rats divided into 4 groups underwent anastomotic construction in ileum and colon at day 0. Three groups received daily oral doses of 20 or 40 mg/kg MMF or saline (control group) from day 0 until the end of the experiment. Half of each group was analyzed after 3 days and half after 7 days. Another group started the medication 3 days after the laparotomy and was analyzed after 7 days, half of this group received 20 mg/kg and half 40 mg/kg MMF. Wound strength in anastomoses and in the abdominal wall was measured using bursting pressure, breaking strength, and histology. Trough levels were measured.

RESULTS: Significant differences in wound strength were seen in ileum tissue after 3 days, which surprisingly showed a stronger anastomosis in the experimental groups. Bursting pressure as well as breaking strength was higher in the low-dose and high-dose MMF group compared with the control group. A negative effect was measured in abdominal wall tissue for the highest-dose group, which disappeared when the medication was delayed for 3 days. Histology showed poorer bridging of the submucosal layer and more polymorphonuclear cell infiltration in the ileum specimens of the control group compared with the treatment groups.

CONCLUSIONS: As a single agent in a preclinical wound healing model in the rat, MMF has no negative effect on healing of bowel anastomoses but might have a negative effect on the healing of abdominal wall.

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