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Polydatin protects against gouty nephropathy by inhibiting renal tubular cell pyroptosis
Xingliang Shi1,2, Lili Zhuang1,2, Zeqing Zhai1,2
1Department of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.
Objective:
To investigate the protective effect and mechanism of polydatin (PD) against gouty nephropathy (GN) in mice.
Methods:
Twenty-four mice were randomly divided into three groups: the control group (no treatment), the GN group (300 mg/kg hypoxanthine + 150 mg/kg potassium oxonate), and the GN + PD group (300 mg/kg hypoxanthine + 150 mg/kg potassium oxonate + 50 mg/kg PD). Histological changes in the kidneys and the levels of uric acid (UA), blood urea nitrogen (BUN), and serum creatinine (SCr) in the sera were measured. In addition, the expression of gasdermin D (GSDMD) protein in renal tubular epithelial cells, and the expression of NOD-like receptor protein 3 (NLRP3), GSDMD, and caspase-1 proteins in the kidney tissues were determined by immunohistochemistry, immunofluorescence, and Western blot.
Results:
In vitro, PD inhibited the expression of NLRP3, caspase-1, and GSDMD and protected the renal tubular epithelial cells from pyroptosis. In vivo, PD treatment significantly ameliorated the pathological changes in kidney tissue, and reversed the decrease of serum UA and BUN in GN model mice. The expression of NLRP3, GSDMD, and caspase-1 proteins was also decreased in the PD-treated GN mice.
Conclusion:
The results suggest that PD has a protective effect on mice with GN, which may be related to the downregulation of NLRP3, GSDMD, and caspase-1 proteins and the inhibition of renal tubular epithelial cells pyroptosis.
Insights
Polydatin (PD) protects against gouty nephropathy (GN) in mice by inhibiting pyroptosis. This involves downregulating NLRP3, caspase-1, and gasdermin D (GSDMD) proteins, offering a potential therapeutic strategy for GN.
Area of Science:
- Nephrology
- Pharmacology
- Cell Biology
Background:
- Gouty nephropathy (GN) is a serious complication of gout, characterized by kidney damage.
- Pyroptosis, a pro-inflammatory form of programmed cell death, plays a significant role in the pathogenesis of GN.
- Identifying therapeutic agents that can mitigate GN progression by targeting pyroptosis is crucial.
Purpose of the Study:
- To investigate the protective effects of polydatin (PD) against gouty nephropathy (GN) in a mouse model.
- To elucidate the underlying mechanism of PD's action, focusing on its impact on pyroptosis and related proteins.
Main Methods:
- A mouse model of GN was established using hypoxanthine and potassium oxonate.
- Mice were treated with polydatin (PD) and compared to control and GN-only groups.
- Kidney histology, serum markers (uric acid, BUN, creatinine), and protein expression (NLRP3, caspase-1, GSDMD) were analyzed.
Main Results:
- Polydatin (PD) treatment significantly ameliorated kidney tissue damage in GN mice.
- PD reversed abnormal levels of serum uric acid and blood urea nitrogen.
- PD inhibited the expression of NLRP3, caspase-1, and GSDMD, thereby reducing renal tubular epithelial cell pyroptosis.
Conclusions:
- Polydatin (PD) demonstrates a significant protective effect against gouty nephropathy (GN) in mice.
- The protective mechanism involves the downregulation of NLRP3, caspase-1, and GSDMD proteins.
- PD's inhibition of pyroptosis suggests its potential as a therapeutic agent for GN.
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