Fig. 4.
The bile acid sensor detects acute liver injuries in mice. (A, B) Chemically induced hepatotoxicity in mice. Wild-type mice were implanted with microencapsulated TGR5/PCREm-SEAP (pPB2/pSP16, 2 × 106 cells, 1 × 104 capsules, 200 cells/capsule)-transgenic HEK-293 cells and received a single oral dose of 1 ml/kg CCl4 (carbon tetrachloride) or 75 mg/kg ANIT (alpha-naphthylisothiocyanate) diluted or dissolved in olive oil (diluent), and (A) total serum bile acid levels or (B) alanine aminotransferase (ALT) activity was measured after 24 h and 48 h. The data are shown as the mean ± SEM, statistics by two-tailed t test, n = 8 mice. ∗∗∗p <0.001 vs. control. (C) Hepatotoxicity-mediated SEAP expression in mice. SEAP levels in the bloodstream of treated mice shown in (A, B) were quantified after 24 h and 48 h. The data are shown as the mean ± SEM, statistics by two-tailed t test, n = 8 mice. ∗∗∗p <0.001 vs. control. (D) Diet insensitivity of the liver-protection device. Wild-type mice were implanted with microencapsulated TGR5/PCREm-SEAP (pPB2/pSP16, 2 × 106 cells, 1 × 104 capsules, 200 cells/capsule)-transgenic HEK-293 cells and kept on standard (5% kcal fat) or high-fat diets (60% kcal fat, Research Diets, cat. no. D12492i) or received twice-daily oral doses of either cholic acid (CA; 20 mg/kg) or tauroursodeoxycholic acid (TUDCA; 20 mg/kg) before blood SEAP levels were quantified after 24 h and 48 h. The data are shown as the mean ± SEM, statistics by two-tailed t test, n = 8 mice. n.s. (not significant) p >0.05 vs. control.