Amanita Phalloides Intoxication Gene Expression Patterns In Mice: Apoptotic and Necrotic Pathways

Abstract

The Amanita phalloides mushroom is the most dangerous in the world, and it induces abrupt liver failure, which is the
main goal of this study. Hepatotoxicity is caused by the most powerful toxin, α-amanitin (α-AMA), which inhibits
RNA polymerase II in hepatocytes and interrupts protein synthesis. Nevertheless, there is a severe lack of sufficient
knowledge about the processes that lead to hepatotoxicity produced by α-AMA. This work seeks to uncover the
intricate processes of necrosis and apoptosis that take place in mouse hepatocytes as a function of the duration of in
vivo exposure to A. phalloides. Methods: The seven-mice BALB-c group was split into five subgroups: control, αAMA-2, α-AMA-12, α-AMA-72, and α-AMA-96. Mice were given an oral dose of A. phalloides mushroom extract
containing 10 mg/kg of α-AMA to simulate poisoning. After 2, 12, 72, and 96 hours, the mice were killed. Afterwards,
the RT-qPCR technique was used to measure the amounts of TNF-α, Bax, caspase-3, and Bcl-2 gene expression in
liver tissues. Additionally, histological evaluations were conducted to assess damage to liver tissues over time. The
findings demonstrated that, when comparing the groups, the levels of the proinflammatory cytokine TNF-α mRNA
expression in mouse liver tissues rose at 2 and 12 hours following A. phalloides administration, according to the RTqPCR data. After ingesting A. phalloides, the levels of Bax mRNA expression spiked at 12 and 72 hours. When
comparing the groups at 72 and 96 hours, we found that caspase-3 mRNA expression levels were higher, but Bcl-2
mRNA expression levels were lower. In conclusion, our results demonstrated that apoptotic mechanisms become
effective after A. phalloides mushroom poisoning, after which necrotic processes emerge. Finally, novel therapeutic
options may be devised by understanding the processes of A. phalloides-induced hepatotoxicity.
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