In high hepatic cholesterol-induced NASH and fibrosis, mitochondrial proteins related to ROS generation, such as cytochrome P450-2E1 (CYP2E), were upregulated,256,257 and Cyp2e1-null mice showed resistance to high cholesterol-induced NASH and fibrosis,256 while ROS clearance proteins, including SOD1, SOD2, Gclc, Gclm and Gpx1, were downregulated.258–262 Silibinin is used for the clinical treatment of NASH because it significantly activates antioxidase activity (CAT, GSH-Px and HO-1) and inhibits pro-oxidase activity (CYP2E1 and CYP4A) to reduce ROS generation.257. Here, GCLM is linked to metabolic dysfunction-associated steatohepatitis.