Ilan Yaron

Bio: Ilan Yaron is an academic researcher. The author has contributed to research in topics: Hepatitis & Chronic liver disease. The author has an hindex of 1, co-authored 1 publications receiving 320 citations.

Ferroptosis driven by radical oxidation of n-6 polyunsaturated fatty acids mediates acetaminophen-induced acute liver failure

Abstract: Acetaminophen (APAP) overdose is a common cause of drug-induced acute liver failure. Although hepatocyte cell death is considered to be the critical event in APAP-induced hepatotoxicity, the underlying mechanism remains unclear. Ferroptosis is a newly discovered type of cell death that is caused by a loss of cellular redox homeostasis. As glutathione (GSH) depletion triggers APAP-induced hepatotoxicity, we investigated the role of ferroptosis in a murine model of APAP-induced acute liver failure. APAP-induced hepatotoxicity (evaluated in terms of ALT, AST, and the histopathological score), lipid peroxidation (4-HNE and MDA), and upregulation of the ferroptosis maker PTGS2 mRNA were markedly prevented by the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1). Fer-1 treatment also completely prevented mortality induced by high-dose APAP. Similarly, APAP-induced hepatotoxicity and lipid peroxidation were prevented by the iron chelator deferoxamine. Using mass spectrometry, we found that lipid peroxides derived from n-6 fatty acids, mainly arachidonic acid, were elevated by APAP, and that auto-oxidation is the predominant mechanism of APAP-derived lipid oxidation. APAP-induced hepatotoxicity was also prevented by genetic inhibition of acyl-CoA synthetase long-chain family member 4 or α-tocopherol supplementation. We found that ferroptosis is responsible for APAP-induced hepatocyte cell death. Our findings provide new insights into the mechanism of APAP-induced hepatotoxicity and suggest that ferroptosis is a potential therapeutic target for APAP-induced acute liver failure.

British Society of Haematology Guidelines on the spectrum of fresh frozen plasma and cryoprecipitate products: their handling and use in various patient groups in the absence of major bleeding

Abstract: Laura Green, Paula Bolton-Maggs, Craig Beattie, Rebecca Cardigan, Yiannis Kallis, Simon J Stanworth, Jecko Thachil and Sharon Zahra NHS Blood and Transplant, Barts Health NHS Trust, Blizard Institute, Queen Mary University of London, London, Serious Hazards of Transfusion Office, Manchester Blood Centre, Manchester, Dept of Anaesthesia, Critical Care and Pain Medicine, Royal Infirmary of Edinburgh, Edinburgh, NHS Blood and Transplant/Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, Department of Hepatology, Barts Health NHS Trust, London, Oxford University Hospitals NHS Trust/NHS Blood and Transplant, University of Oxford, Oxford, Haematology Department, Manchester Royal Infirmary, Manchester, and Scottish National Blood Transfusion Service, Edinburgh, UK