Role of oxidative stress and Homocysteine in Non-Alcoholic Fatty Liver Disease
Author(s): Nikhil D Patel
Abstract: Nonalcoholic fatty liver disease (NAFLD), hepatic manifestation of metabolic syndrome is now the commonest chronic liver disease due to rising obesity and diabetes. NAFLD progresses from simple steatosis (NAFL) to steatohepatitis (NASH) and cirrhosis. In presence of suitable genetic and environmental factors (diet/physical activity/ gut dysbiosis), insulin resistance (IR) and obesity results in adipose dysfunction, which triggers proinflammatory response, decreased lipolysis, increased de-novo lipogenesis and further increased IR. These occasions increment free unsaturated fat (FFA) motion to liver, which prompts triglyceride gathering (NAFL).Toxic levels of FFA in liver trigger increased β-oxidation and mitochondrial dysfunction (MD). Obesity, homocysteine and environmental factors trigger endoplasmic reticulum stress (ERS). MD and ERS result in reactive oxygen species (ROS) production. ROS activates antioxidant mechanisms (consisting of enzymes like Superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione transferase; and non-enzymes like vitamin A, C, E, β-carotene and glutathione) which scavenges them, but over production of ROS results in depletion of antioxidants. Homocysteine adds to ROS production and suppresses antioxidants. Oxidative pressure brings about proinflammatory cytokine creation, lipid peroxidation (estimated by Malondialdehyde) and protein adducts creation prompting cell injury, irritation and cell demise prompting NASH. In addition, it triggers hepatic stellate cell activation leading to fibrosis and subsequently cirrhosis. Oxidative stress also produces DNA damage leading to future hepatocellular carcinoma. Along these lines, oxidative pressure stays key to advancement of NASH and cirrhosis. In clinical practice, differentiating NAFL and NASH requires liver biopsy because non-invasive scoring systems are not sensitive. Measuring homocysteine and enzymes (like glutathione transferase, glutathione peroxidase, catalase, etc.) may prove helpful to define progress to NASH. Also targeting these molecules by newer therapeutic strategies may halt progression of NAFLD.