α-amanitin induces hepatotoxicity via PPAR-γ inhibition and NLRP3 inflammasome activation
Mushroom poisoning, predominantly caused by α-amanitin, is a critical food safety concern in worldwide, with severe cases leading to hepatotoxicity and fatalities. This study delves into the hepatotoxic effects of α-amanitin, focusing on the NLRP3 inflammasome and PPAR-γ's regulatory role in in...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325000855 |
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| author | Haowei Wang Huijie Zhang Lin Miao Chan Wang Hanxin Teng Xiaodong Li Xiaoxing Zhang Genmeng Yang Shangwen Wang Xiaofeng Zeng |
| author_facet | Haowei Wang Huijie Zhang Lin Miao Chan Wang Hanxin Teng Xiaodong Li Xiaoxing Zhang Genmeng Yang Shangwen Wang Xiaofeng Zeng |
| author_sort | Haowei Wang |
| collection | DOAJ |
| description | Mushroom poisoning, predominantly caused by α-amanitin, is a critical food safety concern in worldwide, with severe cases leading to hepatotoxicity and fatalities. This study delves into the hepatotoxic effects of α-amanitin, focusing on the NLRP3 inflammasome and PPAR-γ's regulatory role in inflammation. In vitro studies with L-02 cells showed that α-amanitin reduces cell viability and triggers NLRP3 inflammasome activation, increasing NF-κB phosphorylation and pro-inflammatory cytokines IL-18 and IL-1β. The NLRP3 inhibitor MCC950 mitigated these effects without impacting NF-κB. Conversely, PPAR-γ knockdown intensified the inflammatory response. In vivo, α-amanitin induced dose-dependent liver injury in mice, evident by elevated serum ALT and AST, and histological liver damage. MCC950 pretreatment offered protection against hepatotoxicity, while PPAR-γ inhibition with GW9662 worsened the condition. The study highlights the interplay between α-amanitin, NLRP3, and PPAR-γ in hepatotoxicity, proposing potential therapeutic targets for mushroom poisoning-induced liver diseases. |
| format | Article |
| id | doaj-art-c5a65339893e4a0496ed23ba7035c9a8 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-c5a65339893e4a0496ed23ba7035c9a82025-02-12T05:30:11ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01290117749α-amanitin induces hepatotoxicity via PPAR-γ inhibition and NLRP3 inflammasome activationHaowei Wang0Huijie Zhang1Lin Miao2Chan Wang3Hanxin Teng4Xiaodong Li5Xiaoxing Zhang6Genmeng Yang7Shangwen Wang8Xiaofeng Zeng9Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, ChinaDepartment of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, ChinaDepartment of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, ChinaDepartment of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, ChinaDepartment of Pathogen Biology and Immunology, School of Basic Medical Science, Kunming Medical University, Kunming, ChinaDepartment of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, ChinaDepartment of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, ChinaDepartment of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, China; Correspondence to: Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue Chenggong District, Kunming, Yunnan 650500, China.Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, China; Correspondence to: Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue Chenggong District, Kunming, Yunnan 650500, China.Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, China; Correspondence to: Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue Chenggong District, Kunming, Yunnan 650500, China.Mushroom poisoning, predominantly caused by α-amanitin, is a critical food safety concern in worldwide, with severe cases leading to hepatotoxicity and fatalities. This study delves into the hepatotoxic effects of α-amanitin, focusing on the NLRP3 inflammasome and PPAR-γ's regulatory role in inflammation. In vitro studies with L-02 cells showed that α-amanitin reduces cell viability and triggers NLRP3 inflammasome activation, increasing NF-κB phosphorylation and pro-inflammatory cytokines IL-18 and IL-1β. The NLRP3 inhibitor MCC950 mitigated these effects without impacting NF-κB. Conversely, PPAR-γ knockdown intensified the inflammatory response. In vivo, α-amanitin induced dose-dependent liver injury in mice, evident by elevated serum ALT and AST, and histological liver damage. MCC950 pretreatment offered protection against hepatotoxicity, while PPAR-γ inhibition with GW9662 worsened the condition. The study highlights the interplay between α-amanitin, NLRP3, and PPAR-γ in hepatotoxicity, proposing potential therapeutic targets for mushroom poisoning-induced liver diseases.http://www.sciencedirect.com/science/article/pii/S0147651325000855α-AmanitinHepatotoxicityNLRP3 inflammasomePPAR-γInflammation |
| spellingShingle | Haowei Wang Huijie Zhang Lin Miao Chan Wang Hanxin Teng Xiaodong Li Xiaoxing Zhang Genmeng Yang Shangwen Wang Xiaofeng Zeng α-amanitin induces hepatotoxicity via PPAR-γ inhibition and NLRP3 inflammasome activation Ecotoxicology and Environmental Safety α-Amanitin Hepatotoxicity NLRP3 inflammasome PPAR-γ Inflammation |
| title | α-amanitin induces hepatotoxicity via PPAR-γ inhibition and NLRP3 inflammasome activation |
| title_full | α-amanitin induces hepatotoxicity via PPAR-γ inhibition and NLRP3 inflammasome activation |
| title_fullStr | α-amanitin induces hepatotoxicity via PPAR-γ inhibition and NLRP3 inflammasome activation |
| title_full_unstemmed | α-amanitin induces hepatotoxicity via PPAR-γ inhibition and NLRP3 inflammasome activation |
| title_short | α-amanitin induces hepatotoxicity via PPAR-γ inhibition and NLRP3 inflammasome activation |
| title_sort | α amanitin induces hepatotoxicity via ppar γ inhibition and nlrp3 inflammasome activation |
| topic | α-Amanitin Hepatotoxicity NLRP3 inflammasome PPAR-γ Inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325000855 |
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