Mycophenolate mofetil attenuates uterine ischaemia/reperfusion injury in a rat model

Reprod Biomed Online. 2017 Feb;34(2):115-123. doi: 10.1016/j.rbmo.2016.11.007. Epub 2016 Nov 21.

Abstract

This study evaluated the effect of mycophenolate mofetil (MMF) on uterine tissue preservation following ischaemia/reperfusion (I/R) injury. Uterine I/R injury was induced in rats by clamping the lower abdominal aorta and ovarian arteries for 30 min. Group I/R + V (n = 7) received vehicle alone while Group I/R + M (n = 7) received 20 mg/kg/day MMF. Control groups underwent sham surgery and received vehicle (Group C) or 20 mg/kg/day MMF (Group M) (n = 7 for both). Four hours after detorsion, uterine tissue 8-hydroxy-2'-deoxyguanosine (8-OHdG), glutathione, malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD) and serum ischaemia modified albumin (IMA) concentrations were measured. Histopathological analyses were performed. The I/R + M group showed significant reduction in serum IMA and uterine tissue 8-OHdG, MDA and MPO and significant increase in SOD concentrations compared with the I/R + V group, indicating a protective effect against I/R oxidative damage (P = 0.009, P = 0.006, P = 0.002, P = 0.003 and P = 0.009, respectively). Histopathological evaluation revealed MMF treatment resulted in significantly less tissue and cellular damage and apoptosis compared with the I/R + V group. These results indicate MMF is effective in attenuating uterine tissue damage and preventing apoptosis following uterine I/R injury, probably via anti-inflammatory and anti-oxidative action.

Keywords: mycophenolate mofetil; oxygen species-free radicals; rat; uterine ischaemia-reperfusion; uterine transplantation.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Albumins / metabolism
  • Animals
  • Antibiotics, Antineoplastic / pharmacology*
  • Antioxidants / metabolism
  • Aorta, Abdominal / pathology
  • Arteries / pathology
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Disease Models, Animal
  • Female
  • Glutathione / metabolism
  • Immunosuppressive Agents / therapeutic use
  • Mycophenolic Acid / pharmacology*
  • Ovary / blood supply
  • Peroxidase / metabolism
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / pathology
  • Superoxide Dismutase / metabolism
  • Uterus / pathology*

Substances

  • Albumins
  • Antibiotics, Antineoplastic
  • Antioxidants
  • Immunosuppressive Agents
  • 8-Hydroxy-2'-Deoxyguanosine
  • Peroxidase
  • Superoxide Dismutase
  • Deoxyguanosine
  • Glutathione
  • Mycophenolic Acid