Renal protective effects of 17β-estradiol on mice with acute aristolochic acid nephropathy

Abstract

Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by a Chines herb containing aristolochic acid. Excessive death of renal tubular epithelial cells (RTECs characterized the acute phase of AAN. Therapies for acute AAN were limited, such as steroid and angiotensin-receptor blockers (ARBs)/angiotensin-converting enzyme inhibitors (ACEIs). It wa interesting that, in acute AAN, female patients showed relative slower progression to renal failur than males. In a previous study, female hormone 17--estradiol (E2) was found to attenuate rena ischemia-reperfusion injury. Thus, the aim of this study was to investigate the potential protectiv role of E2 in acute AAN. Compared with male C57BL/6 mice of acute AAN, lower serum creatinin (SCr) and less renal injury, together with RTEC apoptosis in females, were found. Treatment wit E2 in male AAN mice reduced SCr levels and attenuated renal tubular injury and RTEC apoptosis In the mice kidney tissue and human renal proximal tubule cells (HK-2 cells), E2 both attenuate AA-induced cell apoptosis and downregulated the expression of phosphor-p53 (Ser15), p53, an cleaved-caspase-3. This study highlights that E2 exhibited protective effects on the renal injury of acute AAN in male mice by reducing RTEC apoptosis, which might be related to inhibiting the p53 signaling pathway.