Repurposing rupatadine to attenuate ovarian ischemia reperfusion in rats through modulation of PAF/NF-κB/TNF-α/IL-1β; HIF-1α/VEGF/Caspase 3 signaling pathways

Abstract

The aim of the current study is to identify the possible protective effect of rupatadine (RUP) on ovarian ischemia reperfusion (OIR) in rats. RUP was administered in the presence and absence of OIR. Thirty-two adult Wistar albino female rats were randomly arranged into four groups: Sham, RUP (6 mg/kg/day) for 14 days, OIR and OIR + RUP groups.The results demonstrated that OIR significantly lowered serum anti-mullerian hormone level and ovarian total antioxidant capacity. Besides, a significant elevation in serum follicle stimulating hormone, lutenizing hormone, ovarian malondialdehyde level, hypoxia-inducible factor-1(HIF-1α), platelet activating factor (PAF), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and interleukin 1beta (IL-1β) levels along with an evident increase in ovarian vascular endothelial growth factor (VEGF) and caspase-3 immunoexpression. While, OIR + RUP pretreated group showed a reversal in OIR damaging effects in a significant manner in all the aforementioned parameters. Based on these findings; RUP has powerful anti-IR actions by lowering oxidative stress, inflammation, and apoptosis via modulation of the PAF/ NF-κB/TNF-α/ IL-1β; HIF-1α/ VEGF / Caspase 3 signaling pathways. Graphical abstract

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