• Modeling Mechanism：

  Lithocholic acid, as a highly toxic secondary bile acid, induces hepatocyte apoptosis and necrosis by activating the death receptor (Fas) pathway and disrupting mitochondrial function. At the same time, it inhibits the nuclear receptor (CAR/PXR)-mediated detoxification pathway, leading to liver inflammation, cholestasis, and liver function damage.

• Related Products：

  Lithocholic acid (T2202)

• Modeling Method：

  Experimental Subject：

  Mouse, C57BL/6 (WT), CAR⁻/⁻ (CAR knockout), Male, 10 weeks old

  Dosage and Administration Route：

  ① Pre-treatment: CAR agonist (Phenobarbital PB 80 mg/kg, TCPOBOP TC 3 mg/kg) or PXR agonist (PCN 200 mg/kg), Intraperitoneal injection (i.p.), Pre-treatment for 3 days;
  ② Modelling: 125 mg/kg lithocholic acid, Intraperitoneal injection, Continuous co-administration with pre-treatment agents for 3 days

  Dosing Frequency and Duration Model：

  Pre-treatment single dose+modelling twice daily

• Validation：

  Liver function indicators: Serum ALT levels were significantly elevated (73-fold higher in the LCA group of WT mice compared to the control group), and the elevation was even more significant in CAR⁻/⁻ mice (113-fold); CAR/PXR activator pretreatment reduced ALT by 94%-97%; Histological indicators: Multifocal necrosis and diffuse vacuolation were observed in liver tissue, with more severe damage in CAR⁻/⁻ mice, and PB/TC/PCN pretreatment completely alleviated the necrosis; Immune and inflammatory indicators: Cleaved caspase 3 (apoptosis marker) was strongly positive in the cytoplasm of hepatocytes in the LCA group, and PARP cleavage was increased.

*Precautions： All mice were sacrificed 12 hours after modeling, and serum and liver tissue were collected for testing.

*References：Beilke LD,et,al. Decreased apoptosis during CAR-mediated hepatoprotection against lithocholic acid-induced liver injury in mice. Toxicol Lett. 2009 Jul 10;188(1):38-44.