Understanding α-amanitin hepatotoxicity: Mechanisms from cellular models

α-Amanitin (α-AMA), a principal lethal compound in mushroom intoxication, induces hepatotoxicity through multifaceted and complex mechanisms. This review synthesizes current knowledge of α-AMA-induced hepatotoxicity, particularly emphasizing recent advances derived from cellular model studies. Evidence indicates that α-AMA damages hepatocytes through multiple pathways, including RNA polymerase II inhibition, oxidative stress induction, apoptosis and autophagy activation, inflammatory response elicitation, and immunotoxicity. Recent studies have also revealed the involvement of endoplasmic reticulum stress and the N-glycosylation pathway in α-AMA-mediated hepatotoxicity. Although several detoxification agents are available for α-AMA poisoning, their therapeutic efficacy remains suboptimal. A comprehensive elucidation of the cellular mechanisms underlying α-AMA-induced hepatotoxicity is essential for developing more effective therapeutic strategies. Future research should prioritize the exploration of these mechanisms and leverage high-throughput screening and gene-editing technologies to identify novel therapeutic targets and advance the development of more efficacious detoxification agents.