A team of researchers led by China has discovered that a commonly used medical dye shows promise in reducing the toxic effects of death cap mushrooms, potentially leading to the development of the first targeted antidote for these deadly fungi. Although the dye has already received approval from the US Food and Drug Administration (FDA) for other applications, it has yet to be tested as an antidote in humans. The researchers believe that this discovery could save numerous lives since death cap mushrooms, scientifically known as Amanita phalloides, are responsible for more than 90 percent of mushroom poisoning fatalities worldwide. Consuming just half of a death cap mushroom can lead to severe liver or kidney failure.
In their study, published in the journal Nature Communications, the team focused on targeting alpha-amanitin, the primary toxin produced by death cap mushrooms. They employed genome-wide CRISPR screening, a relatively new technique used to investigate the roles of specific genes in infections and poisonings. This technology had previously aided in the discovery of a potential antidote for box jellyfish venom, one of the most dangerous toxins found in animals. Through CRISPR screening, the researchers identified the protein STT3B as a key contributor to the toxic effects of death cap mushroom poisoning.
To find a substance capable of inhibiting this protein, the researchers screened a database of drugs already approved by the FDA. They identified indocyanine green, a fluorescent dye administered intravenously, which has been widely used in diagnostic imaging to assess liver and heart function. This unexpected connection surprised the research team. They conducted tests using the antidote on liver cells in a petri dish and then on mice. In both cases, the dye demonstrated significant potential in mitigating the toxic impact of mushroom poisoning.
Qiaoping Wang, a researcher at Sun Yat-sen University in China and the senior author of the study, expressed optimism about the findings, stating that the molecule holds immense potential for treating human cases of mushroom poisoning. The researchers plan to proceed with human trials using indocyanine green as an antidote for death cap mushrooms. While an extract from milk thistle seeds known as silibinin has been used in the past to treat death cap poisoning, its exact mechanism of action remains unclear. The potential antidote discovered in this study, if proven effective in humans, could serve as the first targeted antidote for death cap mushroom poisoning and save numerous lives.
