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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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325000855 |
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| Summary: | 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. |
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| ISSN: | 0147-6513 |