Mechanism and treatment of α-amanitin poisoning

Xue, Jinfang; Lou, Xiran; Ning, Deyuan; Shao, Ruifei; Chen, Guobing

doi:10.1007/s00204-022-03396-x

Cited by 10 publications

(2 citation statements)

References 87 publications

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“…We showed that ICG could effectively prevent AMA-induced cell death and increase resistance to AMA in vitro. The enterohepatic cycle of AMA could significantly influence the clinical course of amatoxin poisoning in humans and animals 61 . Interruption of enterohepatic circulation such as biliary drainage has become an alternative detoxification method 62 .…”

Section: Discussionmentioning

confidence: 99%

Identification of indocyanine green as a STT3B inhibitor against mushroom α-amanitin cytotoxicity

Wang

Wan

et al. 2023

Nat Commun

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The “death cap”, Amanita phalloides, is the world’s most poisonous mushroom, responsible for 90% of mushroom-related fatalities. The most fatal component of the death cap is α-amanitin. Despite its lethal effect, the exact mechanisms of how α-amanitin poisons humans remain unclear, leading to no specific antidote available for treatment. Here we show that STT3B is required for α-amanitin toxicity and its inhibitor, indocyanine green (ICG), can be used as a specific antidote. By combining a genome-wide CRISPR screen with an in silico drug screening and in vivo functional validation, we discover that N-glycan biosynthesis pathway and its key component, STT3B, play a crucial role in α-amanitin toxicity and that ICG is a STT3B inhibitor. Furthermore, we demonstrate that ICG is effective in blocking the toxic effect of α-amanitin in cells, liver organoids, and male mice, resulting in an overall increase in animal survival. Together, by combining a genome-wide CRISPR screen for α-amanitin toxicity with an in silico drug screen and functional validation in vivo, our study highlights ICG as a STT3B inhibitor against the mushroom toxin.

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Section: Discussionmentioning

confidence: 99%

Identification of indocyanine green as a STT3B inhibitor against mushroom α-amanitin cytotoxicity

Wang

Wan

et al. 2023

Nat Commun

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“…While AMA has been shown to cause damage to both the liver and kidneys, the liver stands out as the predominant affected target organ according to AMA toxicokinetic performance [4]. Furthermore, the main target and its primary biological target are thought to be RNA polymerase II in liver cells [5]. However, other studies have reported that an inhibition of RNA polymerase II by AMA is not the only mechanism by which liver injury can occur [6,7].…”

Section: Introductionmentioning

confidence: 99%

Metabolomic Insights into the Mechanisms of Ganoderic Acid: Protection against α-Amanitin-Induced Liver Injury

Zheng,

Lv,

et al. 2023

Metabolites

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α-Amanitin is a representative toxin found in the Amanita genus of mushrooms, and the consumption of mushrooms containing α-Amanitin can lead to severe liver damage. In this study, we conduct toxicological experiments to validate the protective effects of Ganoderic acid A against α-amanitin-induced liver damage. By establishing animal models with different durations of Ganoderic acid A treatment and conducting a metabolomic analysis of the serum samples, we further confirmed the differences in serum metabolites between the AMA+GA and AMA groups. The analysis of differential serum metabolites after the Ganoderic acid A intervention suggests that Ganoderic acid A may intervene in α-amanitin-induced liver damage by participating in the regulation of retinol metabolism, tyrosine and tryptophan biosynthesis, fatty acid biosynthesis, sphingosine biosynthesis, spermidine and spermine biosynthesis, and branched-chain amino acid metabolism. This provides initial insights into the protective intervention mechanisms of GA against α-amanitin-induced liver damage and offers new avenues for the development of therapeutic drugs for α-Amanitin poisoning.

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Transforming toxins into treatments: the revolutionary role of α-amanitin in cancer therapy

Ning,

Xue,

Lou

et al. 2024

Arch Toxicol

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Mechanism and treatment of α-amanitin poisoning

Cited by 10 publications

References 87 publications

Identification of indocyanine green as a STT3B inhibitor against mushroom α-amanitin cytotoxicity

Identification of indocyanine green as a STT3B inhibitor against mushroom α-amanitin cytotoxicity

Metabolomic Insights into the Mechanisms of Ganoderic Acid: Protection against α-Amanitin-Induced Liver Injury

Transforming toxins into treatments: the revolutionary role of α-amanitin in cancer therapy

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