Underlying mechanisms behind the protective effect of angiotensin (1–7) in experimental rat model of ovarian ischemia reperfusion injury

Abstract

AimsOvarian ischemia as a consequence of torsion constitutes a gynecologic emergency affecting females during reproductive age. Its management by detorsion results in ovarian ischemia-reperfusion (IR) injury. Thus, a conservative treatment with detorsion is highly recommended. Therefore, we attempted to investigate the effect and underlying mechanisms of angiotensin 1–7 (Ang-(1–7)) treatment against ovarian IR injury. Main methodsFemale rats were included into: Sham group; Ang-(1–7) (300 μg/kg, i.p.) group; ovarian IR groups with and without Ang-(1–7) treatment. We determined ovarian Ang-(1–7), malondialdehyde (MDA) and nitric oxide (NO) in addition to serum total anti-oxidant capacity (TAC) levels. Ovarian gene expressions of angiotensin converting enzyme 2 (ACE2), Mas receptor, tumor necrosis factor alpha (TNF-α) and B-cell leukemia/lymphoma-2 (BCL-2) were estimated. Furthermore, histopathological changes and ovarian expressions of nuclear factor kappa B (NF-κB), inducible and endothelial nitric oxide synthases (iNOS and eNOS) were done. Key findingsTreatment of ovarian IR rats with Ang-(1–7) led to marked improvement of ovarian damage through histological examination which was accompanied with marked increase in ovarian Ang-(1–7) level and expressions of ACE2 and Mas receptor, decrease in MDA and NO levels and expressions of NF–kB, iNOS and TNF-α with increase in serum TAC levels and ovarian expressions of eNOS and BCL-2. SignificanceOur results proved the protective effect of Ang-(1–7) against ovarian IR injury in rats and this may be attributed to ACE2/Ang (1–7)/Mas axis which showed anti-oxidant, anti-inflammatory and anti-apoptotic effects. Therefore, Ang-(1–7) can be used in the future for treatment of ovarian IR injury.