Ameliorative effect of nicorandil in ovarian ischemia-reperfusion–induced injury in rats: role of potassium channel

Abstract

Ovarian torsion is a gynecological emergency that leads to serious outcomes. Nicorandil (NIC) is an ATP-sensitive potassium (KATP) channel activator that protects the heart from ischemia. The current study aimed to investigate the role and mechanism of action of NIC in ovarian ischemia-reperfusion (OIR) and possible KATP participation. Twenty-four female albino rats were classified into 4 groups: sham control, OIR, OIR + NIC, OIR + NIC+ glibenclamide (GLB) groups. Serum anti-Müllerian hormone (AMH), ovarian malondialdehyde (MDA), total nitrites (NOx) contents, and superoxide dismutase (SOD) activity were evaluated. Bax and Bcl2 mRNA were also assessed. Histological and immunohistochemical (anti-COX-2 and anti CD68) studies were done. The OIR non-treated group showed histopathological ovarian injury with decreased AMH level. Ovarian MDA, NOx, and Bax mRNA and the expression of COX-2 and CD68 were increased; however, SOD activity and Bcl2 mRNA level were decreased by OIR. NIC significantly ameliorated the histopathological ovarian injury with the restoration of AMH level. NIC significantly corrected oxidative stress and apoptotic biomarkers with decreased COX-2 and CD68 immunostaining. GLB co-administration significantly decreased the protection afforded by NIC. These results imply that NIC has a protective role against OIR via antioxidant, anti-inflammatory, and anti-apoptotic effects and such protection relies, at least partially, on the KATP channel.

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Acknowledgments

The authors would like to thank Dr Nagwa Mohammed Zynhom, Lecturer of biochemistry, Biochemistry Department, Faculty of Medicine, Minia University, Egypt, for her kind help and support in the PCR determination part.

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SA, MA, and WY conceived and designed research. SA conducted experiments. WY wrote the manuscript. SM performed and wrote the part of histopathology, immunohistochemistry. MA revised the manuscript. All authors read and approved the manuscript.

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Correspondence to Walaa Yehia Abdelzaher.

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The experiments were conducted in accordance with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and the protocol was approved by the Faculty of Medicine, Minia University Ethics Committee, for the Care and Use of Laboratory Animals.

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Abdel-Gaber, S.AW., Atta, M., Abdel-Hafez, S.M.N. et al. Ameliorative effect of nicorandil in ovarian ischemia-reperfusion–induced injury in rats: role of potassium channel. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1599–1610 (2020). https://doi.org/10.1007/s00210-020-01854-w

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Keywords

  • Ovarian ischemia
  • Nicorandil
  • Glibenclamide
  • Potassium channel
  • Oxidative stress