The role of oxidative stress in chronic liver diseases

The liver plays a central role in the biotransformation of a variety of drugs and xenobiotics. During the biotransformation of drugs and chemicals, the liver generates various reactive intermediates and in turn attacks the hepatocyte membrane to generate free radicals such as superoxide, hydroxyl, peroxyl, hydrogen peroxide, peroxynitrite, peroxynitrous acid, etc. Hepatic stellate cells (HSCs), also known as perisinusoidal cells or Ito cells play a central role in the onset of various forms of chronic liver diseases. The free radicals liberated during biotransformation in the liver activate the quiescent HSCs into myofibroblast-like phenotype responsible for the excessive synthesis of extracellular matrix proteins that cause hepatic fibrosis, cirrhosis, portal hypertension, and hepatocellular carcinoma. On the other hand, hepatocytes also have several first-line intracellular antioxidant defenses such as superoxide dismutase, catalase, and glutathione and detoxifying enzymes to neutralize/protect the free radicals generated during oxidative stress. During chronic liver injury, the redox homeostasis is altered, and an enormous amount of free radicals are released with the concomitant decrease in the intracellular antioxidants causing oxidative stress. This chapter summarizes the molecular mechanisms of oxidative stress-induced chronic liver diseases.