Sulforaphane alleviates membranous nephropathy by inhibiting oxidative stress-associated podocyte pyroptosis
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...
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| Format: | Article |
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Mashhad University of Medical Sciences
2025-02-01
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| Series: | Iranian Journal of Basic Medical Sciences |
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| Online Access: | https://ijbms.mums.ac.ir/article_25231_2dbd19502a8656c7c14dbc01690e99df.pdf |
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| author | Daoyuan Lv Laping Chu Yuan Du Chunqing Li Neng Bao Yuqing Su Gang Wang Yanlie Zheng Yafen Yu |
| author_facet | Daoyuan Lv Laping Chu Yuan Du Chunqing Li Neng Bao Yuqing Su Gang Wang Yanlie Zheng Yafen Yu |
| author_sort | Daoyuan Lv |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-fec0ba262b004045b7106f096bb2bfd2 |
| institution | Kabale University |
| issn | 2008-3866 2008-3874 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj-art-fec0ba262b004045b7106f096bb2bfd22025-08-20T03:35:48ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742025-02-0128223724410.22038/ijbms.2024.78960.1708325231Sulforaphane alleviates membranous nephropathy by inhibiting oxidative stress-associated podocyte pyroptosisDaoyuan Lv0Laping Chu1Yuan Du2Chunqing Li3Neng Bao4Yuqing Su5Gang Wang6Yanlie Zheng7Yafen Yu8Department of Nephrology, Affiliated Hospital of Jiangnan University, Wuxi, ChinaDepartment of Nephrology, Affiliated Hospital of Jiangnan University, Wuxi, ChinaDepartment of Nephrology, Affiliated Hospital of Jiangnan University, Wuxi, ChinaDepartment of Nephrology, Affiliated Hospital of Jiangnan University, Wuxi, ChinaDepartment of Nephrology, Affiliated Hospital of Jiangnan University, Wuxi, ChinaDepartment of Nephrology, Affiliated Hospital of Jiangnan University, Wuxi, ChinaDepartment of Nephrology, Jiangmen Central Hospital, Jiangmen, ChinaDepartment of Infectious Disease, General Hospital of Southern Theater Command, Guangzhou, ChinaDepartment of Nephrology, Affiliated Hospital of Jiangnan University, Wuxi, ChinaObjective(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.https://ijbms.mums.ac.ir/article_25231_2dbd19502a8656c7c14dbc01690e99df.pdfmembranous nephropathyoxidative stresspodocytepyroptosissulforaphane |
| spellingShingle | Daoyuan Lv Laping Chu Yuan Du Chunqing Li Neng Bao Yuqing Su Gang Wang Yanlie Zheng Yafen Yu Sulforaphane alleviates membranous nephropathy by inhibiting oxidative stress-associated podocyte pyroptosis Iranian Journal of Basic Medical Sciences membranous nephropathy oxidative stress podocyte pyroptosis sulforaphane |
| title | Sulforaphane alleviates membranous nephropathy by inhibiting oxidative stress-associated podocyte pyroptosis |
| title_full | Sulforaphane alleviates membranous nephropathy by inhibiting oxidative stress-associated podocyte pyroptosis |
| title_fullStr | Sulforaphane alleviates membranous nephropathy by inhibiting oxidative stress-associated podocyte pyroptosis |
| title_full_unstemmed | Sulforaphane alleviates membranous nephropathy by inhibiting oxidative stress-associated podocyte pyroptosis |
| title_short | Sulforaphane alleviates membranous nephropathy by inhibiting oxidative stress-associated podocyte pyroptosis |
| title_sort | sulforaphane alleviates membranous nephropathy by inhibiting oxidative stress associated podocyte pyroptosis |
| topic | membranous nephropathy oxidative stress podocyte pyroptosis sulforaphane |
| url | https://ijbms.mums.ac.ir/article_25231_2dbd19502a8656c7c14dbc01690e99df.pdf |
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