Question
Discuss the mechanism of hepatotoxicity caused by the following toxicants:
(i) Carbon tetrachloride (ii) Paracetamol
Answer :
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Hepatotoxicity refers to liver damage caused by various toxicants. Among these, carbon tetrachloride (CCl₄) and paracetamol are well-known agents that induce liver injury through distinct mechanisms. Carbon tetrachloride (CCl₄) is a volatile organic compound that has been widely used as a solvent, but it is highly toxic to the liver. When inhaled or ingested, CCl₄ is metabolized in the liver, primarily by the cytochrome P450 enzyme system (CYP2E1). This enzyme converts CCl₄ into a highly reactive radical, the trichloromethyl radical (CCl₃•), and its corresponding peroxy radical (CCl₃OO•). These radicals are extremely toxic and initiate a cascade of events leading to hepatotoxicity. The reactive radicals interact with cellular components, including lipids, proteins, and nucleic acids. This results in the formation of lipid peroxides, which damage cellular membranes and disrupt the integrity of hepatocytes. The damage to hepatocyte membranes leads to the release of intracellular enzymes like alanine transaminase (ALT) and aspartate transaminase (AST) into the bloodstream, which serves as biomarkers for liver injury. Additionally, the reactive metabolites of CCl₄ induce oxidative stress by generating reactive oxygen species (ROS),
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