Related Experiment Video
Updated: Mar 13, 2026
Ovariectomy and 17β-estradiol Replacement in Rats and Mice: A Visual Demonstration
Published on: June 7, 2012
Renal Protective Effects of 17β-Estradiol on Mice with Acute Aristolochic Acid Nephropathy
Min Shi1, Liang Ma2,3, Li Zhou4,5
1Division of Nephrology, Department of Internal Medicine, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China. minshi0616@163.com.
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.
Insights
17β-estradiol (E2) may protect male mice from aristolochic acid nephropathy (AAN). E2 reduced kidney injury and renal tubular epithelial cell apoptosis, potentially by inhibiting the p53 pathway.
Area of Science:
- Nephrology
- Toxicology
- Endocrinology
Background:
- Aristolochic acid nephropathy (AAN) is a progressive kidney disease causing renal tubular epithelial cell (RTEC) death.
- Current therapies for acute AAN are limited.
- Female patients with AAN exhibit slower progression, suggesting a potential protective role of female hormones.
Purpose of the Study:
- To investigate the protective role of 17β-estradiol (E2) in acute aristolochic acid nephropathy (AAN).
Main Methods:
- Male C57BL/6 mice with acute AAN were used.
- E2 treatment was administered to male AAN mice.
- Renal injury, RTEC apoptosis, serum creatinine (SCr), and p53 signaling pathway markers were assessed in kidney tissue and HK-2 cells.
Main Results:
- Female mice with AAN showed less renal injury and RTEC apoptosis compared to males.
- E2 treatment in male AAN mice reduced SCr levels and attenuated renal tubular injury and RTEC apoptosis.
- E2 decreased aristolochic acid-induced apoptosis and downregulated p-p53, p53, and cleaved-caspase-3 expression.
Conclusions:
- 17β-estradiol (E2) demonstrates protective effects against acute aristolochic acid nephropathy (AAN) in male mice.
- E2 reduces RTEC apoptosis, potentially through the inhibition of the p53 signaling pathway.
More Related Videos
10:15Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection
Published on: November 10, 2021
09:33Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018