Blockade of endothelin receptors with bosentan limits ischaemia/reperfusion-induced injury in rat ovaries

Abstract

Objective: To investigate the role of endothelin receptors in ovarian ischaemia/reperfusion (I/R) injury in rats using the endothelin receptor antagonist bosentan.

Study design: Group 1: sham operation; Group 2: sham operation and bosentan 60 mg/kg; Group 3: bilateral ovarian ischaemia; Group 4: 3-h period of ischaemia followed by 3h of reperfusion; Groups 5 and 6: bosentan 30 and 60 mg/kg, respectively, with bilateral ovarian ischaemia applied 30 min later; the bilateral ovaries were removed after 3h of ischaemia; Groups 7 and 8: 3h of bilateral ovarian ischaemia was applied, with bosentan 30 and 60 mg/kg, respectively, administered 2.5h after the induction of ischaemia; following the 3-h period of ischaemia, 3h of reperfusion was applied, after which the ovaries were removed.

Results: Ischaemia and I/R decreased superoxide dismutase (SOD) activity and the level of glutathione (GSH) in ovarian tissue, but increased the level of malondialdehyde (MDA) significantly compared with the sham operation group. Bosentan 30 and 60 mg/kg before ischaemia and I/R decreased the MDA level and increased SOD activity and the GSH level in the experimental groups. The serum levels of the inflammatory cytokines interleukin (IL)-1β, IL-6 and tumour necrosis factor-α were also measured in the I/R injury model in rat ovaries. The levels of these cytokines were significantly higher in the ischaemia and I/R groups compared with the sham operation and sham operation plus bosentan groups. The histopathological findings also demonstrated the protective role of bosentan against I/R-induced injury in rat ovaries.

Conclusion: Administration of bosentan protects the ovaries against oxidative damage and I/R-induced injury.

Keywords: Bosentan; Endothelin; Ischaemia/reperfusion; Ovarian; Oxidative stress.