β hydroxycyclodextrin

To study the inhibitory effect of Notch inhibitor, male C57BL/6 mice (20–22 g) were treated with a single intraperitoneal injection of CCl₄ (1 ml/kg in olive oil) at day 1.Olive-oil treated mice were used as controls. At day 2 and day 3, CCl₄-treated mice intraperitoneally received 10 mg/kg Avagacestat prepared in 1% DMSO (Sigma) and 5% β-hydroxycyclodextrin (Sigma) or vehicle treatment (1%DMSO/5%β-hydroxycyclodextrin/PBS) (n = 5 per group). At day 4, all mice were sacrificed and livers were harvested for subsequent analysis.
Progressive 4 and 8 weeks model has been established in Balb/c mice while C57BL/6 mouse strain was used for acute liver injury model. From our experience, C57BL/6 mice have high mortality, following 4–8 weeks CCl₄ treatment and leads to multi-organ fibrosis. While CCl₄ administration in Balb/c mice, leads to slow and progressive fibrosis and hence are not suitable for acute liver injury model. Therefore, we have established acute liver injury model in C57BL/6 to have early liver fibrogenesis and Balb/c for progressive (advanced) fibrosis. The difference between these mice strains lies in the differences in Th1 and Th2 responses42 (link). Th1-dominance response in C57BL/6 strain and heightened Th2-responses in Balb/c mice determine the severity of liver fibrosis in these mice strains.

To study the effect of WP1066, male C57BL/6 mice were treated with a single intraperitoneal injection of olive oil or CCl₄ (1 mL/kg in olive‐oil) at day 1. At day 2 and day 3, CCl₄‐treated mice received intraperitoneal administration of 5 mg/kg WP1066 prepared in 1% DMSO (Sigma) and 5% β‐hydroxy cyclodextrin (Sigma) or vehicle treatment (1%DMSO/5% β‐hydroxy cyclodextrin/PBS) (n = 5 per group). At day 4, all mice were sacrificed, and livers were harvested for the subsequent analysis.

To study the effect of BIBF1120, male C57BL/6 mice were treated with a single intraperitoneal injection of olive-oil or CCl₄ (1 ml/kg in olive-oil) at day 1. At day 2 and day 3, CCl₄-treated mice received intra-peritoneal administration of 5 mg/kg tyrosine kinase inhibitor BIBF1120 (Selleckchem, Boston, NY) prepared in 1% DMSO (Sigma) and 5% β-hydroxycyclodextrin (Sigma) or vehicle treatment (1%DMSO/5%β-hydroxycyclodextrin/PBS) (n = 5 per group). At day 4, all mice were sacrificed and livers were harvested for the subsequent analysis. Alanine Transaminase (ALT) levels in the plasma was measured using ALT Colorimetric Activity Assay Kit (Cayman Chemical Company, Michigan, MI, USA) as per manufacturer’s instructions.