Fig. 3.

Control (nonhumanized) (n = 6) or chimeric (n = 6) TK-NOG mice were treated with 160 mg/kg per day bosentan by mouth or vehicle for 28 days, and their weights were measured on a daily basis (A). The plasma ALT (B), alkaline phosphatase, and GGT (C) levels were measured after 4 weeks of dosing. The plasma ALT levels were also measured after 1 and 2 weeks in (B). In (B and C), each bar is the average + S.D. of six measurements in control or humanized TK-NOG mice, and the dashed line indicates the upper limit of normal for the measured parameter. (D) Bosentan treatment induces an increase in plasma total bile acids in humanized TK-NOG mice. Plasma was collected from both control (n = 3) and humanized (n = 3) TK-NOG mice after 0 and 28 days of treatment with bosentan (160 mg/kg per day). After 28 days of bosentan treatment, the total plasma bile acid concentration in humanized mice was increased 5-fold (P = 0.046), whereas in control mice there was no change in the plasma total bile acid concentration (P = 0.38).