An investigation of the effects of metformin on ovarian ischemia-reperfusion injury in rats

Topcu A. , BALIK G. , ATAK M. , Mercantepe T. , UYDU H. A. , Tumkaya L.

EUROPEAN JOURNAL OF PHARMACOLOGY, vol.865, 2019 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 865
  • Publication Date: 2019
  • Doi Number: 10.1016/j.ejphar.2019.172790


Damage to the ovaries or tissue torsion can significantly reduce the ovarian reserve and thus cause severe gynecological and hormonal deficiencies. The discovery of new agents is always needed in the treatment of this condition. Metformin (MET) has been shown to be beneficial in attenuating ovarian ischemia-reperfusion injury. Fifty-six female Sprague Dawley rats were divided into seven groups. Group 1 represented the control group (C), Group 2, the ischemia group (I), and Group 3, the ischemia/reperfusion group (I/R). Group 4, the ischemia (I) + 250 group, and Group 5, the ischemia (I) + 500 group, received 250 mg/kg and 500 mg/kg MET, respectively. Group 6, the ischemia/reperfusion (I/R) + 250 group, and Group 7, the ischemia/reperfusion (I/R) + 500 group, received 250 mg/kg and 500 mg/kg MET, respectively. Tissue malondialdehyde (MDA), glutathione (GSH), and tumor necrosis factor-alpha (TNF-alpha) levels in ovarian tissue increased following I/R, while estradiol (E-2) levels decreased. Moreover, infiltration and diffuse edematous areas were observed in addition to diffuse vascular congestion and hemorrhage findings. Caspase-3 and nuclear factor kappa B (NF-kappa beta) expression levels also increased. MDA and TNF-alpha concentrations decreased in the MET treatment groups, while GSH and E-2 levels increased. The findings showed that I/R causes ovarian damage through the induction of oxidative stress, inflammation, and apoptosis. However, MET application was effective in preventing damage in ovarian tissue by reducing levels of reactive oxygen species, proinflammatory cytokines, caspase-3 and NF-kappa beta.