title: Prevention of infertility induced by ovarian ischemia reperfusion injury by benidipine in rats: Biochemical, gene expression, histopathological and immunohistochemical evaluation.
abstract: BACKGROUND
  Benidipine has been reported to prevent the ischemia/reperfusion (I/R) damage in heart tissue and to suppress oxidant and proinflammatory cytokine production, increased by I/R. However, There was no information about the effects of benidipine on I/R injury in the ovary and the damage of I/R-induced infertility.
  
  
  OBJECTIVE
  The aim of the study was to investigate the effects of benidipine on bilateral ovarian I/R injury and whether or not effective in the treatment of I/R-induced infertility in rats.
  
  
  METHODS
  Forty-eight females, albino Wistar rats were randomly divided into 4 groups: IRC group (ovarian I/R group, n=12), IRB-2 group (ovarian I/R+2mg/kg benidipine group, n=12), IRB-4 group (ovarian I/R+4mg/kg benidipine group, n=12) and HG group (healthy group with sham operation, n=12). In IRB-2 and IRB-4 groups, two hours ischemia and two hours reperfusion was performed following orally benidipine administration. After this I/R procedure, 6 rats from each group performed bilateral overectomy. Ovarian levels of malondialdehyde (MDA) and total glutathione (tGSH), ovarian gene expressions of interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) and also apoptosis were evaluated. The other 6 rats from each group were put in together with six male rats in separated cages for 2 months in order to reproduce. During this period, rats which did not become pregnant were accepted as infertile.
  
  
  RESULTS
  MDA levels, expressions of TNF-α and IL-1β in IRC group were significantly higher than in the SGA group and tGSH was decreased. In total, 4mg/kg benidipine has better prevented ovaries from the increase of oxidants and proinflammatory cytokines, the decrease of antioxidants than 2mg/kg benedipine. In the histopathological examination hemorrhage, congestion, follicle degeneration, neutrophil infiltration and necrosis were seen in ovarian tissue of IRC group. Only dilated and congested blood vessels were found in the IRB-2 group. No histopathological finding was encountered in the IRB-4 group. I/R caused infertility in rats. In total, 4mg/kg benidipine prevented from infertility better than the dose of 2mg/kg benedipine.
  
  
  CONCLUSIONS
  In total, 4mg/kg benidipine reduced I/R injury and I/R-related infertility more significantly compared to 2mg/kg benedipine in rat ovaries.
authors.affiliation: Department of obstetrics and gynecology, Etlik Zubeyde Hanim education and research hospital, Ankara, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Unlubilgin
authors.affiliation: Department of pharmacology, faculty of medicine, Erzincan university, 24030 Erzincan, Turkey.
authors.forename: B
authors.initials: B
authors.lastname: Suleyman
authors.affiliation: Department of pathology, Mengucek Gazi training and research hospital, Erzincan, Turkey.
authors.forename: G
authors.initials: G
authors.lastname: Balci
authors.affiliation: Department of obstetrics and gynecology, faculty of medicine, Ataturk university, Erzurum, Turkey.
authors.forename: R
authors.initials: R
authors.lastname: Atakan Al
authors.affiliation: Department of biology, faculty of arts and sciences, Erzincan university, Erzincan, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Cankaya
authors.affiliation: Department of obstetrics and gynecology, faculty of medicine, Erzincan university, Erzincan, Turkey.
authors.forename: U
authors.initials: U
authors.lastname: Arslan Nayki
authors.affiliation: Department of pharmacology, faculty of medicine, Erzincan university, 24030 Erzincan, Turkey. Electronic address: halis.suleyman@gmail.com.
authors.forename: H
authors.initials: H
authors.lastname: Suleyman
mesh_terms: D000818:Animals; D017209:Apoptosis; D004095:Dihydropyridines / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D005978:Glutathione / Q000378:metabolism; D007247:Infertility, Female / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D023421:Models, Animal; D010053:Ovary / Q000098:blood supply* / Q000378:metabolism; D017208:Rats, Wistar; D015427:Reperfusion Injury; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D004095:Dihydropyridines; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; C061004:benidipine; D008315:Malondialdehyde; D005978:Glutathione
keywords: Benidipine; Ischemia; Ovary; Rat; Reperfusion