Deciphering Molecular Mechanisms of Carbon Tetrachloride-
Induced Hepatotoxicity: A Brief Systematic Review

Muhammad   Mazhar   Fareed; Hina      Khalid; Sana      Khalid; Sergey      Shityakov

doi:10.2174/0115665240257603230919103539

Abstract

The liver plays a critical role in metabolic processes, making it vulnerable to injury. Researchers often study carbon tetrachloride (CCl₄)-induced hepatotoxicity in model organisms because it closely resembles human liver damage. This toxicity occurs due to the activation of various cytochromes, including CYP2E1, CYP2B1, CYP2B2, and possibly CYP3A, which produce the trichloromethyl radical (CCl₃*). CCl₃* can attach to biological molecules such as lipids, proteins, and nucleic acids, impairing lipid metabolism and leading to fatty degeneration. It can also combine with DNA to initiate hepatic carcinogenesis. When exposed to oxygen, CCl₃* generates more reactive CCl₃OO*, which leads to lipid peroxidation and membrane damage. At the molecular level, CCl₄ induces the release of several inflammatory cytokines, including TNF-α and NO, which can either help or harm hepatotoxicity through cellular apoptosis. TGF-β contributes to fibrogenesis, while IL-6 and IL-10 aid in recovery by minimizing anti-apoptotic activity and directing cells toward regeneration. To prevent liver damage, different interventions can be employed, such as antioxidants, mitogenic agents, and the maintenance of calcium sequestration. Drugs that prevent CCl₄- induced cytotoxicity and proliferation or enhance CYP450 activity may offer a protective response against hepatic carcinoma.

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DOI https://dx.doi.org/10.2174/0115665240257603230919103539	Print ISSN 1566-5240
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Deciphering Molecular Mechanisms of Carbon Tetrachloride- Induced Hepatotoxicity: A Brief Systematic Review

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