Excess superoxide could be generated within injured mitochondria through electron leakage, and the resulting excess of superoxide would be converted to hydrogen peroxide by Sod2. Gpxs or CAT can metabolize hydrogen peroxide to nontoxic H2O, but the Fenton and/or Haber-Weiss reactions mediated by iron generate highly reactive toxic ROS, hydroxyl radicals. Levels of iron are elevated in NASH, which is an inducer of oxidative stress, and reduced iron levels result in fair outcomes for patients with chronic liver diseases. L-carnitine supplementation in NASH patients greatly improved glucose plasma levels, lipid profiles, and histological manifestations. Furthermore, L-carnitine ameliorated fatty liver in high-calorie diet/streptozotocin-induced type 2 BEZ235 citations diabetic mice by improving mitochondrial function. We assumed that L-carnitine may alter not only the LCFA uptake into mitochondria, but also the activity of the ROS-scavenging antioxidant enzymes in NASH model mice. The present data showed that Lcarnitine reinforced the mitochondrial b-oxidation and the activity of the key ROS-scavenging antioxidant enzymes such as Sod2 and CAT without an increase in oxidative stress. In addition, Lcarnitine has recently been shown to exhibit ammonia reduction in hepatic encephalopathy patients and improvement of fatigue, which reflects the wide pharmacological effects of L-carnitine on hepatic and muscular mitochondrial function recovery. We were not able to demonstrate such effects of L-carnitine in our model, as we did not examine plasma ammonia levels or physical scores that reflect hepatic encephalopathy and related effects. The role of a-tocopherol in the treatment of NASH is based on its activity as a free-radical scavenger. a-tocopherol is a chainbreaking antioxidant in free-radical reactions, which is an important step in lipid peroxidation and membrane stabilization. Animal studies have shown that a-tocopherol improves fibrosis, reduces mitochondrial lipid peroxidation, and corrects oxidative stress in animal models of liver disease associated with oxidative injury. However, the life-long administration of atocopherol to animals exposed to cold or warm stress resulted in a significantly shortened life span. In humans, several randomized controlled trials have indicated a potential role for vitamin E supplementation in NAFLD. These studies included biochemical data and liver histological assessment, but they lasted for only several years. Many cerebrovascular disease studies have investigated the effects of vitamin E. A meta-analysis of the effect of vitamin E on stroke revealed a 10% reduction in ischemic stroke accompanied by a 22% increase in hemorrhagic stroke. Furthermore, meta-analysis revealed that all-cause mortality with vitamin E and vitamin A supplementation was worse than for controls. Our data showed that a-tocopherol increased mitochondrial b-oxidation-related enzyme gene expression without increased oxidative stress or altered activity of key ROS-scavenging antioxidant enzymes such as Sod2 and Gpx4. Overall, the trend was stronger in the L-carnitine group.