Thioacetamide (TAA) undergoes bioactivation in the liver by the CYP450 2E1 enzyme, resulting in the formation of TAA-S-oxide and TAA-S-dioxide. TAA-S-dioxide induces oxidative stress via lipid peroxidation of the hepatocellular membrane. A single TAA dose (50–300 mg/kg) administration initiates hepatocellular necrosis around the pericentral region after its covalent binding to macromolecules in the liver. Intermittent TAA administration (150–300 mg/kg, weekly thrice, for 11–16 weeks) activates transforming growth factor (TGF)-β/smad3 downstream signaling in injured hepatocytes, causing hepatic stellate cells (HSCs) to acquire myofibroblast like phenotype. The activated HSCs synthesize a variety of extracellular matrix, leading to liver fibrosis, cirrhosis, and portal hypertension. The TAA induced liver injury varies depending on the animal model, dosage, frequency, and routes of administration. However, TAA induces hepatotoxicity in a reproducible manner, and it is an ideal model to evaluate the antioxidant, cytoprotective, and antifibrotic compounds in experimental animals.

硫代乙酰胺 (TAA) 在肝脏中通过 CYP450 2E1 酶进行生物活化，导致形成 TAA-S-氧化物和 TAA-S-二氧化物。TAA-S-dioxide 通过肝细胞膜的脂质过氧化诱导氧化应激。单次 TAA 剂量（50-300 mg/kg）给药会在其与肝脏中的大分子共价结合后引发中心周围区域周围的肝细胞坏死。间歇性给予 TAA（150-300 mg/kg，每周三次，持续 11-16 周）可激活受损肝细胞中的转化生长因子 (TGF)-β/smad3 下游信号，导致肝星状细胞 (HSC) 获得肌成纤维细胞样表型。活化的 HSCs 合成多种细胞外基质，导致肝纤维化、肝硬化和门静脉高压症。TAA诱导的肝损伤因动物模型而异，剂量、频率和给药途径。然而，TAA 以可重复的方式诱导肝毒性，它是在实验动物中评估抗氧化、细胞保护和抗纤维化化合物的理想模型。