Keap1 Deletion Rescues Cell Death Associated With Gpx4 Loss in Hepatocytes During Acute Liver Injury

BACKGROUND & AIMS: Acute liver failure (ALF) is a life-threatening condition with limited treatment options beyond liver transplantation in non-acetaminophen cases. The extensive loss of liver function results from severe hepatocyte death, where elevated reactive oxygen species (ROS) play a significant role. Nuclear factor erythroid-2 like 2 (Nrf2) is crucial in ROS defence by regulating genes like glutathione peroxidase 4 (GPX4), which prevents lipid peroxidation (LPO). GPX4 is involved in several regulated cell processes, including apoptosis and ferroptosis. METHODS: GPX4 expression was measured in liver samples from healthy, ALF, and acute-on-chronic liver failure (ACLF) patients. To investigate GPX4's role, mice with hepatocyte-specific deletion of Gpx4 (Gpx4(

• Colyn, L.
• Grube, J.
• Wang, C.
• Dietrich, J.
• Kühnel, M.
• Reinders, J.
• Edlund, K.
• Jonigk, D.
• Gaßler, N.
• Hengstler, J.
• Trautwein, C.