Protective effect of estradiol copreservation against kidney ischemia-reperfusion injury

Ischemia-reperfusion injury (IRI) is the major cause of delayed graft function (DGF) during the posttransplantation 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. The autologous kidney transplant model in rats was first established. Rats were divided into 5 groups: normal group (N), sham group (sham), static cold storage (SCS) 4 hours group (control), SCS 4 hours + ethanol (1 mu L/mL) group (solvent), and SCS 4 hours + ethanol (1 mu L/mL) + E2 (1000 ng/mL) group (E2). ER alpha expression under hypothermia was measured by western blotting. Moreover, biochemical analyses 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 ERa, 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. E2 copreservation upregulated ERa expression under hypothermia. Moreover, E2 copreservation reduced levels of creatinine and BUN in plasma but without affecting estradiol and testosterone. Further, E2 copreservation increased expression of eNOS and antiapoptotic Bcl-2 and decreases expression of proapoptotic Bax. E2 copreservation significantly inhibited IRI-induced apoptosis and evidently improved pathological severity in the kidney of rats. E2 copreservation exerts protective activity against IRI-induced pro-inflammatory and proapoptotic effects in kidneys during organ preservation time and improves transplanted kidney function.