Intravenous rifampicin use in the management of amanita phalloides toxicity

Zuker-Herman, Rona; Tong, Roger; Wong, Anselm

doi:10.1080/15563650.2021.1887492

Cited by 4 publications

(3 citation statements)

References 9 publications

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“…The "death cap" Amanita is the most toxic mushroom in the world, responsible for 90% of mushroom-related fatalities. 1 α-Amanitin is the most lethal component in Amanita, which primarily targets the liver and ultimately leads to acute liver failure. Currently, there is no specific antidote available for amanitin poisoning, and most developed drugs lack satisfactory clinical efficacy.…”

Section: Introductionmentioning

confidence: 99%

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Salidroside Inhibits α-Amanitin-Induced AML-12 Cell Apoptosis via the Regulation of PINK1/Parkin-Mediated Mitophagy and Mitochondrial Function

Zhou,

Wang,

Zhao

et al. 2024

Chem. Res. Toxicol.

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Poisoning caused by the mushroom Amanita phalloides, due to the toxin αamanitin, accounts for approximately 90% of food poisoning deaths in China with no specific antidotes. To investigate the role of salidroside (Sal) in α-amanitin (α-AMA)induced mitophagy, mouse liver cells AML-12 were exposed to α-AMA in the presence of Sal or not. Intracellular reactive oxygen species (ROS) levels were measured using a ROS detection kit, mitochondrial activity was evaluated using a mitochondrial red fluorescent probe kit or JC-1 dye, and protein expression levels of PINK1, Parkin, LC3 II, P62, Bax, Bcl-2, Caspase 3, Cleaved-Caspase 3, PARP I, and Cleaved-PARP I were detected through Western blot. Results demonstrated that α-AMA led to increased intracellular ROS levels, cell apoptosis, and decreased mitochondrial membrane potential. Notably, expression levels of mitophagy-related proteins PINK1, Parkin, and LC3 increased significantly while the P62 protein expression decreased remarkably. Furthermore, Sal reversed the α-AMAinduced decrease in cell viability and mitochondrial membrane potential and increase in intracellular ROS level. In addition, Sal promoted expression levels of PINK1, Parkin, and LC3 II while suppressing the Bax/Bcl-2 ratio, Cleaved-Caspase 3, and Cleaved-PARP I as well as P62. The results above proved that salidroside alleviates α-AMA-induced mouse liver cells damage via promoting PINK1/Parkin-mediated mitophagy and reducing cell apoptosis.

show abstract

Section: Introductionmentioning

confidence: 99%

“…The “death cap” Amanita is the most toxic mushroom in the world, responsible for 90% of mushroom-related fatalities . α-Amanitin is the most lethal component in Amanita , which primarily targets the liver and ultimately leads to acute liver failure.…”

Section: Introductionmentioning

confidence: 99%

Salidroside Inhibits α-Amanitin-Induced AML-12 Cell Apoptosis via the Regulation of PINK1/Parkin-Mediated Mitophagy and Mitochondrial Function

Zhou,

Wang,

Zhao

et al. 2024

Chem. Res. Toxicol.

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“…A total of 10,036 exposure events, resulting in 38,676 illnesses and 788 deaths, were reported between 2010 and 2020 in China 3 . Among all poisonous mushrooms, death caps ( Amanita phalloides ) are responsible for more than 90% of death 4 . Amatoxin poisoning is commonly associated with poor outcomes, mainly owing to the irreparable acute failure of the liver or kidney 5 , 6 .…”

Section: Introductionmentioning

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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Silibinin: a toxicologist’s herbal medicine?

Horowitz

2022

Clinical Toxicology

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Intravenous rifampicin use in the management of amanita phalloides toxicity

Cited by 4 publications

References 9 publications

Salidroside Inhibits α-Amanitin-Induced AML-12 Cell Apoptosis via the Regulation of PINK1/Parkin-Mediated Mitophagy and Mitochondrial Function

Salidroside Inhibits α-Amanitin-Induced AML-12 Cell Apoptosis via the Regulation of PINK1/Parkin-Mediated Mitophagy and Mitochondrial Function

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

Silibinin: a toxicologist’s herbal medicine?

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