Serelaxin alleviates ischemia reperfusion-induced kidney injury by modulating inflammatory response and inhibiting of notch-2/hes-1 signaling pathway

Background: Renal transplantation is the last standard option for the treatment of patients with end-stage renal failure. During renal transplantation, the renal damage occurs after a short time of warm ischemia after the harvest of the kidney from the donor, a long period of the cold ischemia through cryopreservation and a last phase of the warm ischemia through recipient implantation. Ischemia reperfusion (IR) complications are one of the challenges of transplantation. Objectives: The study aimed to diagnose the protective effect of serelaxin against kidney damage induced by IR and to understand the possible impact of the Notch-2/Hes-1 signaling pathway in this problem. Methods: Eighteen Sprague Dawley rats were divided into three groups: serelaxin group was treated with serelaxin (5?g/kg SC), while the control group was treated with distilled water and the sham group was not treated with serelaxin or D.W. The renoprotective effect of serelaxin was studied by assessing the kidney function by measuring of serum urea and creatinine. The anti-inflammatory impact, was evaluated by measurement of interleukin-1?. Also the effect of serelaxin on Notch-2/Hes-1 pathway in ischemia reperfusion injury was investigated. Results: The results disclosed that serelaxin pretreatment remarkably restored S.u, S.cr, and ameliorated kidney damage. Through IHC, the result showed that serelaxin produced a magic effect against IRI through downregulated the protein expression of cytoplasmic and nuclear cleaved Notch-2 in addition to nuclear Hes-1. Serelaxin also produced potent anti-inflammatory effect via the reduction in the protein expression of the IL-1?. Conclusion: These results highlight the nephroprotective effects of serelaxin against IRI by numerous pathways that also include Notch-2/Hes1. These novel findings uphold the use of serelaxin or serelaxin derived agents as a promising medication for those illnesses in which IRI is the main pathogen.