In vivo and in vitro ?-amanitin metabolism studies using molecular networking

Amanitin poisonings are among the most life-threatening mushroom poisonings, and mainly caused by genus Amanita. Hepatotoxicity is hallmark of amanitins, powerful toxins contained in these mushrooms, can require liver transplant. Among amatoxins, ?-amanitin studied. However, hypothesis a possible metabolism amanitins still controversial this pathophysiology. Therefore, there need clarification using cutting-edge tools allowing study. Molecular network has emerged as tool study through organization representation untargeted tandem mass spectrometry (MS/MS) data graphical form. The aim to investigate amanitin molecular networking. In vivo (four positive urine samples) vitro (differentiated HepaRG cells supernatant incubated with 2 ?M for 24 h) samples were extracted analyzed LC-HRMS/MS Q Exactive™ Orbitrap spectrometer. Using networking on both vivo, we have demonstrated that does not undergo human. Thus, provide solid evidence production metabolites cannot be involved its toxicity pathways. These findings help settle debate toxicity.