In search of an antidote to poisonous mushrooms


Foragers around the world are looking to wild mushrooms to bring their earthy, nutty, and meaty flavors to the table. But more often than not, people mistake a potentially deadly species for an edible species.

A fungus called a death cap – Amanita phalloides – and dozens of related species that contain the same toxin, alpha amanitin, are responsible for the vast majority of mushroom poisoning deaths. Many scientists have tried to find a quick cure.

“There is no antidote,” said Terrence Delaney, a plant biologist and mycologist at the University of Vermont who studies the toxic profiles of a related mushroom called the destroying angel.

In the past, such poisoning was fatal in more than half of cases, but today approximately 85 to 90 percent of people survive. The main treatment is water, because the toxin is excreted in the urine, Dr. Delaney said, and it also contains electrolytes and substances to protect the liver. “But a lot of people don’t get better, and the only effective treatment is a liver transplant,” he said.

Over the years, researchers have proposed and tested several treatments, said Dr. Delaney, adding, “Frankly, none of these therapies are convincing.”

Alpha Amanitine wreaks havoc in the body by impairing the ability of cells to produce messenger RNA. Messenger RNA builds proteins, and without new proteins, the cell machinery shuts down. When the toxin circulates in the body, it causes severe damage to the liver.

Researchers have very little idea how the toxin does its dirty work, said Qiaoping Wang, a pharmacologist and toxicologist at Sun Yat-sen University in Shenzhen, China.

Dr. Wang and his colleagues are not themselves foragers. However, they are working to scan the genome to look for the chains of biological events triggered by the toxins, as well as the molecules that prevent them. in Study published On Tuesday in Nature Communication, they report finding a promising molecule that appears to block some of the toxic effects of alpha-amanitine.

Researchers have for the first time used CRISPR, a gene-editing technology, to create human cells with thousands of specific genes knocked out, one by one. Then they doused the cells with alpha-amanitin and tracked which cells continued to thrive. They concluded that if cells’ life is more rosy when a specific gene is disabled, that gene may be involved in fighting off the toxin. They narrowed down one gene, STT3B, that seemed particularly important for toxicity.

Next, the researchers used computer modeling to search for FDA-approved compounds that might inhibit STT3B, and came up with 34 potential drugs. All but one fell through further tests on the cells.

The remaining compound, called indocyanine green (ICG), is a dye widely used to take pictures of liver and heart function. When Dr. Wang and his team injected the toxin into mice, followed by ICG, the animals’ recovery improved and liver damage decreased dramatically.

“The exact mechanism is still unknown,” said Dr. Wang. But his team’s work so far suggests that the STTB3 gene somehow helps alpha-amanitin enter cells, and that ICG inhibits this step.

“It’s an amazingly beautiful leaf,” said Ann Pringle, a mycologist and geneticist at the University of Wisconsin, Madison, who has studied death caps for 20 years. “They do such an incredible amount of work and end up with this premise that they’ve found an antidote.”

Whether the compound will work in people remains to be seen, Dr. Pringle said, but it’s a good starting point. “I love that they took it all the way to a mouse model,” she said, “because that’s a lot more than what I’ve seen with some of these other ideas that have come and gone.”

The effectiveness of ICG also depends on the interval between injecting the toxin and receiving the drug; Potential cure is diminished if given after more than four hours.

Often, people don’t know they’ve eaten a poisonous mushroom like death’s cap until eight or more hours later because they don’t feel sick until then, Dr. Delaney said. After experiencing some severe gastrointestinal symptoms, people undergo two to three days in which they feel much better. But all the while, the poison continues to cause damage.

Dr. Delaney is part of a global network of experts who run a Facebook group called Poison help. Identify the contingency of mushrooms and plants.

People ask the group to identify death caps or related mushrooms. Last year, he remembers, a boy told his relatives that he had eaten a marshmallow he found in the yard. The family realized what had happened, took him to the emergency room, and asked the Facebook group to identify the mushroom. Knowing what it was, the doctors provided proper care and the boy recovered.

“We are really good at quickly identifying Amanitas and almost always provide responses within 15 minutes,” he said.

Treatment or not, Dr. Delaney said, “early knowledge that someone has taken one of these medications is absolutely essential.”


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