首页|Molecular mechanisms in thioacetamide-induced acute and chronic liver injury models

Molecular mechanisms in thioacetamide-induced acute and chronic liver injury models

扫码查看
原文链接
  • NETL
  • NSTL
  • Elsevier
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 hepa-tocellular membrane. A single TAA dose (50-300 mgAg) administration initiates hepatocellular necrosis around the pericentral region after its covalent binding to macromolecules in the liver. Intermittent TAA administration (150-300 mgAg, 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.

ThioacetamideOxidative stressLiver necrosisLiver fibrosis

Devaraj Ezhilarasan

展开 >

Department of Pharmacology, Molecular Medicine and Toxicology Lab, Saveetha Denial College, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu 600077, India

2023

10.1016/j.etap.2023.104093

Environmental toxicology and pharmacology

Environmental toxicology and pharmacology

SCI
ISSN：1382-6689
年,卷(期)：2023.99(Apr.)
  • 7
  • 103