Losartan ameliorates premature ovarian failure by regulation of the Sirti1/NF-κB pathway in female albino rats.

OBJECTIVES: Recently, cancer rates have increased among women of reproductive age. As a result, chemotherapy exposure is a common cause of premature ovarian failure (POF). The present study evaluated Losartan's protective effects against cyclophosphamide (CP)-induced POF.

METHODS AND RESULTS: Forty female nuligravid Sprague-Dawley rats were used. Rats were randomly placed in four groups: Group I (control group); Group II (losartan group); received Losartan 100 mg/kg daily by gavage oraly for 30 days; Group III (POF group): POF was induced by intraperitoneal injection of 50 mg/kg of CP on day one of the experiment and then 8 mg/kg/day for fifteen serial days; Group IV (Losartan + POF group): received losartan 100 mg/kg daily for thirty days one hour before CP intraperitoneal dosage of 50 mg/kg on the first day of the experiment and then CP has given in a dose of 8 mg/kg/day for fifteen successive days. Physiological sera of blood and tissue samples were evaluated biochemically, hormonally, and histopathologically at the end of the experiment. Losartan treatment improved E2, FSH, LH, and oxidative stress biomarkers. Furthermore, coadministration of Losartan to the POF group exhibited a significant lessening in systolic blood pressure, a significant improvement in ovarian blood flow velocity, and a significant decline in ovarian vascular resistance related to the POF group. Furthermore, Losartan reduced the histopathological and immunohistochemical alterations, enhanced SIRT1 gene expression, and decreased NF-κB gene expression.

DISCUSSION: Our findings suggest that Losartan protects rats from cyclophosphamide-induced ovarian toxicity.