Protective effect of estradiol copreservation against kidney ischemia‐reperfusion injury

Background Ischemia-reperfusion injury (IRI) is the major cause of delayed graft function (DGF) during the post-transplantation period. Estradiol (E2) prevents IRI-induced kidney dysfunction and tissue injury. However, many side-effects limit E2's in vivo application. Recent evidence uncovers E2's expanded use in the field of transplantation. We aimed to study if and how E2 exerts protective activity during the period of kidney organ preservation. Methods The autologous kidney transplant model in rats was first established. Rats were divided into 5 groups, which were normal group (N), sham group (Sham), static cold storage (SCS) 4 h group (Control), SCS 4 h + ethanol (1 µl/mL) group (Solvent), and SCS 4 h + ethanol (1 µl/mL) + E2 (1000 ng/mL) group (E2). ERα expression under hypothermia was measured by western blotting. Moreover, biochemical analysis of plasma levels of Creatinine, BUN, Estradiol, and testosterone were examined. Among all groups, kidney tissues were collected and processed for further western blot analysis about ERα, eNOS, Bcl-2, and Bax expression, histological analyses such as H&E staining to evaluate pathological severity. In addition, a TUNEL assay is performed to evaluate apoptosis. Results E2 co-preservation up-regulated ERα expression under hypothermia. Moreover, E2 co-preservation reduced levels of Creatinine and BUN in plasma but without affecting estradiol and testosterone. Further, E2 co-preservation increased expression of eNOS and anti-apoptotic Bcl-2, and decreases expression of pro-apoptotic Bax. E2 co-preservation significantly inhibited IRI-induced apoptosis and evidently improved pathological severity in the kidney of rats. Conclusions E2 co-preservation exerts protective activity against IRI-induced pro-inflammatory and pro-apoptotic effects in kidneys during organ preservation time and improves transplanted kidney function.