Sulforaphane alleviates membranous nephropathy by inhibiting oxidative stress-associated podocyte pyroptosis

Document Type : Original Article

Authors

1 Department of Nephrology, Affiliated Hospital of Jiangnan University, Wuxi, China

2 Wuxi School of Medicine, Jiangnan University, Wuxi, China

3 Department of Nephrology, Jiangmen Central Hospital, Jiangmen, China

4 Department of Infectious Disease, General Hospital of Southern Theater Command, Guangzhou, China

10.22038/ijbms.2024.78960.17083

Abstract

Objective(s): To investigate the natural product sulforaphane (SFN) in protection of membranous nephropathy (MN) by inhibiting oxidative stress-associated podocyte pyroptosis. 
Materials and Methods: A passive Heymann nephritis (PHN) model was established and treated with SFN. Clinical manifestations were examined by testing 24-hr urine protein, albumin, total cholesterol, triglyceride, high-density and low-density lipoprotein levels. Podocyte injury was observed through glomerular ultrastructure and the expression of podocin and desmin. Intrarenal oxidative stress was evaluated through assessment of oxidative markers, including malondialdehyde, 8-isoprostane, and 8-hydroxydeoxyguanosine, and the activities of anti-oxidant enzymes, including total superoxide dismutase, catalase, and γ-glutamylcysteine synthetase. Podocyte and intrarenal pyroptosis were investigated by observing the localization of the GSDMD N-terminus (GSDMD(N)) in podocytes; the expression of pyroptosis signaling pathway, including GSDMD, NF-κB p65, p-NF-κB p65 (Ser536), NLRP3, ASC, caspase-1, IL-1β, and IL-18; and pyroptosis encounter Nrf2 in the glomeruli and kidney. 
Results: SFN has a protective effect on MN, as reflected by alleviation of nephrotic syndrome, amelioration of podocyte foot process fusion, increased expression and normalization of podocin, and decreased expression of desmin in the glomeruli. Mechanistically, SFN relieved intrarenal oxidative stress, as indicated by decreased renal malondialdehyde, 8-isoprostane, and 8-hydroxydeoxyguanosine and increased activity of total superoxide dismutase, catalase, and γ-glutamylcysteine synthetase. SFN also inhibited podocyte and intrarenal pyroptosis, as revealed by decreased colocalization of GSDMD (N) with synaptopodin and ZO-1, decreased expression of pyroptosis signaling pathway, and increased expression of Nrf2 in the glomeruli and kidney. 
Conclusion: SFN could alleviate MN by inhibiting oxidative stress-associated podocyte pyroptosis.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences
Volume 28, Issue 2
February 2025
Pages 237-244

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