The Selective Estrogen Receptor Modulator, Raloxifene, Is Protective Against Renal Ischemia–reperfusion Injury

Abstract

Background. There is increasing evidence that estrogen is responsible for improved outcomes in female kidney transplant recipients. Although the exact mechanism is not yet known, estrogen appears to exert its protective effects by ameliorating ischemia–reperfusion injury (IRI). In this study, we have examined whether the beneficial effects of exogenous estrogen in renal IRI are replicated by therapy with any one of several selective estrogen receptor modulators. Methods. C57BL/6 adult mice underwent standardized warm renal ischemia for 28 min after being injected with the selective estrogen receptor modulators, raloxifene, lasofoxifene, tamoxifen, bazedoxifene, or control vehicle (dimethyl sulfoxide), at 16 and 1 h before IRI. Plasma concentrations of blood urea nitrogen and creatinine were assessed 24, 48, 72, and 96 h post-IRI. Tissue was collected 30 d postischemia for fibrosis analysis using Sirius Red staining. Results. Raloxifene treatment in female mice resulted in significantly lower blood urea nitrogen and creatinine after IRI and significantly lower fibrosis 30 d following IRI. Conclusions. Raloxifene is protective against both acute kidney injury and fibrosis resulting from renal IRI in a mouse model.

The potential renoprotective effect of Raloxifene in renal ischemia-reperfusion injury in a male rat model

“…One study showed significantly less renal interstitial fibrosis in the RAL-treated group than in controls. In another study, RAL reduced renal tubular damage in a mice model with hereditary glomerulonephritis [38]. This renoprotective effect in rats can be explained by the ability of RAL to alter the balance of antioxidants by reducing levels of oxidative stress and increasing redox system activity.…”

The combinatorial effect of age and biological sex on alloimmunity and transplantation outcome

“…In young females, estrogens play a predominantly protective role, ameliorating the consequences of IRI while the protective effects of estrogens may be less pronounced with aging (54,66). In support, pre-clinical studies investigating the effects of selective estrogen receptor modulators and treatment suggest that the loss of protection in aging could at least in part be preserved (55,67).…”