In our previous research, we successfully established a nonalcoholic steatohepatitis (NASH) model in high fat diet (HFD)-fed mice by multiple intraperitoneal administrations of carbon tetrachloride (CCl4) and liver X receptor agonist (LXR-a) over a 28-day period, allowing effective evaluation of drug efficacy. However, future usage of CCl4 in research may become restricted because it is an ozone-depleting substance. Therefore, in this study, we aimed to develop a NASH model with rapid onset of liver fibrosis using thioacetamide (TAA) as a substitute for CCl4.
Male C57BL/6J mice (7 weeks old) were fed with a high fat diet (HFD-60) for 28 days. TAA at 100 mg/kg, TAA at 200 mg/kg, or CCl4 was administered on days 16, 20, 24, and 28 of HFD feeding. Additionally, LXR-a was administered consecutively for 5 days from day 24 of HFD feeding. On the final day of HFD feeding, insulin tolerance testing was performed. Blood samples and the liver were then collected for measurements of AST, ALT, and TG concentrations in the serum and histopathological examination of the liver.
Administering TAA and LXR-a during the 28-day HFD feeding led to increased AST, ALT, and TG levels, indicating heightened insulin resistance. Additionally, liver fat accumulation and fibrosis were observed. Therefore, a NASH model with rapid-onset of liver fibrosis was established using TAA as a substitute for CCl4.