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Carbon tetrachloride (CCl₄) is a classic hepatotoxicant whose toxicity is primarily mediated through its metabolism in the liver. Upon entering hepatocytes, CCl₄ undergoes bioactivation by the cytochrome P450 enzyme system, particularly CYP2E1, to form the highly reactive trichloromethyl free radical (CCl₃•). This radical can react with cellular macromolecules including lipids, proteins, and nucleic acids, initiating lipid peroxidation of the endoplasmic reticulum and other membranous structures. Lipid peroxidation disrupts membrane integrity, leading to increased permeability, leakage of cellular enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and eventual hepatocyte necrosis. The trichloromethyl radical can further react with oxygen to form the trichloromethyl peroxy radical (CCl₃OO•), which exacerbates oxidative _________ _________ ____ __________ _______ _____ _________ __________ ______ _____.
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