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Molecules 2016, 21(10), 1391; doi:10.3390/molecules21101391

Renal Protective Effects of 17β-Estradiol on Mice with Acute Aristolochic Acid Nephropathy

1
,
1,2
,
1,2,* and 1,2,*
1
Division of Nephrology, Department of Internal Medicine, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China
2
Kidney Research Institute, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Diego Muñoz-Torrero
Received: 24 August 2016 / Revised: 5 October 2016 / Accepted: 13 October 2016 / Published: 18 October 2016
(This article belongs to the Section Medicinal Chemistry)
View Full-Text   |   Download PDF [11987 KB, uploaded 18 October 2016]   |  

Abstract

Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by a Chinese 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 steroids and angiotensin-receptor blockers (ARBs)/angiotensin-converting enzyme inhibitors (ACEIs). It was interesting that, in acute AAN, female patients showed relative slower progression to renal failure than males. In a previous study, female hormone 17β-estradiol (E2) was found to attenuate renal ischemia-reperfusion injury. Thus, the aim of this study was to investigate the potential protective role of E2 in acute AAN. Compared with male C57BL/6 mice of acute AAN, lower serum creatinine (SCr) and less renal injury, together with RTEC apoptosis in females, were found. Treatment with 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 attenuated AA-induced cell apoptosis and downregulated the expression of phosphor-p53 (Ser15), p53, and 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. View Full-Text
Keywords: estradiol; aristolochic acid nephropathy; apoptosis; renal tubular epithelial cell; p53 estradiol; aristolochic acid nephropathy; apoptosis; renal tubular epithelial cell; p53
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Shi, M.; Ma, L.; Zhou, L.; Fu, P. Renal Protective Effects of 17β-Estradiol on Mice with Acute Aristolochic Acid Nephropathy. Molecules 2016, 21, 1391.

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