Impact of Enoxaparin +α Lipoic acid combination on oxidative stress, follicle development and apoptotic damage in ovarian ischemia reperfusion model

M. Dogan Ozcil, O. Ozcan, S. Hakverdi, H.S. Bayraktar, E. Dirican, F. Kacmaz

Department of Obstetrics and Gynecology, Department of Medical Biochemistry, Department of Pathology, Tayfur Ata Sökmen Faculty of Medicine, Experimental Research Application and Research Center, Department of Biostatistics, Tayfur Ata Sökmen Faculty of Medicine, Department of Molecular Biochemistry and Genetics, Health Sciences Institute, Hatay Mustafa Kemal Üniversitesi, Antakya, Hatay, Turkey. mustafadoganozcil2@gmail.com

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• Gynecology

OBJECTIVE: With this study we aimed at investigating the impact of enoxaparin (E) and α-lipoic acid (α-LA) on ischemia/reperfusion (I/R) damage in an experimental ovarian torsion (T) detorsion (D) model.

MATERIALS AND METHODS: The study comprised 80 female albino rats aged 12 weeks. They were divided into 8 groups as follows, with 10 rats in each group: Group 1 (Sham), Group 2 (Ischemia, 3 hours), Group 3 (I/R, 6 hours reperfusion), Group 4 (I/R, 3 days reperfusion), Group 5 (I/R, E, 6 hours), Group 6 (I/R, E, 3 days), Group 7 (I/R, E+α-LA, 6 hours), and Group 8 (I/R, E+α-LA, 3 days). Immediately after detorsion, enoxaparin (0.5 mg/kg/day, sc) or α-LA (100 mg/kg/day, ip) were administered. Ovarian levels of malondialdehyde (MDA), glutathione peroxidase (GPx), and catalase were measured. In addition to total Antioxidant Status (TAS) and Total Oxidative Stress (TOS), the Oxidative Stress Index (OSI) was calculated. Serum levels of AMH, FSH, LH, E2, and progesterone were measured. Ovarian samples were histopathologically examined and they underwent Tag staining for apoptosis.

RESULTS: Compared with the sham group, there was a significant increase in TOS, OSI, and MDA levels in I/R group (p<0.001). Compared to Group 2, a significant increase was determined in TOS and OSI in Group 3 (p<0.05). In Group 4, a significant increase was found compared to Group 2 (p<0.01). The lowest level of I/R damage and the highest level of antioxidants were found in Group 2, 7, and 8. The highest values of TOS, OSI, and MDA were found in Group 3, Group 4, Group 5, and Group 6 (p<0.001). When the sham group and Group 4 were compared, it was found that AMH and E2 levels decreased (p<0.001), while FSH levels increased (p<0.001). In Group 6, AMH and E2 values were significantly decreased compared to the sham group (p<0.001). In the histopathological examination, the findings were observed to be parallel to those of the biochemical markers.

CONCLUSIONS: Combined use of α-Lipoic acid and enoxaparin prevents oxidative stress and ovarian damage due to ischemia-reperfusion injury better than the use of drugs alone.

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