Rivastigmine Attenuates Doxorubicin-Induced Ovarian Injury in Rats Associated with Modulation of α7nAChR/NF-κB/TNF-α/Caspase-3 Signaling.

Abstract

The present study aimed to investigate the potential protective effect of rivastigmine (RIVA) against doxorubicin (DOX)-induced ovarian injury in female rats, with particular emphasis on its anti-inflammatory, antioxidant, and antiapoptotic effects. Thirty-two adult female albino rats were randomly divided into four groups: control, RIVA (0.3mg/kg, intraperitoneally), DOX (10mg/kg, intraperitoneally), and RIVA+DOX groups. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Müllerian hormone (AMH) levels, as well as Alpha-7 Nicotinic Acetylcholine Receptor (α7nAChR) gene expression, were assessed. Ovarian oxidative stress, inflammatory, and apoptotic biomarkers were also evaluated. Histopathological examination of the ovaries and immunohistochemical assessment of caspase-3 expression were performed. DOX significantly increased serum FSH and LH levels and ovarian oxidative stress, inflammatory, and apoptotic biomarkers, while decreasing serum AMH levels and α7nAChR gene expression. These changes were accompanied by marked ovarian histopathological alterations and increased caspase-3 immunoexpression. RIVA significantly attenuated the DOX-induced alterations in hormonal levels, α7nAChR gene expression, oxidative stress, inflammatory, and apoptotic biomarkers, with improvement in ovarian histopathology and reduction of caspase-3 immunoexpression. Overall, the protective effect of RIVA against DOX-induced ovarian injury was associated with modulation of α7nAChR/NF-κB/TNF-α/caspase-3 signaling, suggesting the involvement of this pathway in its protective effects.