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, CCl4induces 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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破译四氯化碳诱导肝毒性的分子机制：简要系统综述


肝脏在代谢过程中起着至关重要的作用，因此很容易受伤。研究人员经常在模型生物体中研究四氯化碳 (CCl4) 诱导的肝毒性，因为它与人类肝脏损伤非常相似。这种毒性是由于各种细胞色素的激活而发生的，包括 CYP2E1、CYP2B1、CYP2B2 和可能的 CYP3A，它们会产生三氯甲基自由基 (CCl3*)。 CCl3* 可以附着在脂质、蛋白质和核酸等生物分子上，损害脂质代谢并导致脂肪变性。它还可以与DNA结合引发肝癌。当暴露于氧气时，CCl3* 会产生更具反应性的 CCl3OO*，从而导致脂质过氧化和膜损伤。在分子水平上，CCl4 诱导多种炎症细胞因子的释放，包括 TNF-α 和 NO，它们可以通过细胞凋亡帮助或损害肝毒性。 TGF-β 有助于纤维形成，而 IL-6 和 IL-10 通过最大限度地减少抗凋亡活性并引导细胞再生来帮助恢复。为了预防肝损伤，可以采用不同的干预措施，例如抗氧化剂、促有丝分裂剂和维持钙固存。防止 CCl4 诱导的细胞毒性和增殖或增强 CYP450 活性的药物可能提供针对肝癌的保护性反应。