Novel Mechanism of Cytochrome P450 2E1 Inhibition Protect

Supplementary data

Figure 1. Metabolism of isnoazid in the liver.

Figure 2. Plasma concentration time plots of chlorzoxazone (CZX) (A) and 6-hydroxyl-CZX (6-OH CZX) (B) for normal control (NC), isoniazid (INH)/rifampicin (RIF)-Control, Study-LK, and Study-HK groups after 3 weeks of treatment. The INH/RIF group has a higher area under the curve for 6-OH CZX as compared to all other groups. Data are shown as mean ± SD. Each group contained at least 8 mice.

Table 1. Mortality and clinical observations in male mice.

Items / Dose (mg/kg) / Incidence during the study period (n'/n') / Total Incidence (n/n)
D1 after dosing (hours) / D2-D14
0 / 1 / 2 / 3 / 4
Mortality / 0 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6
100 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6
1000 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6
10000 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6
Clinical signs
Hypoactivity / 0 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6
100 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6
1000 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6
10000 / 1/6 / 2/6 / 0/6 / 0/6 / 0/6 / 0/6 / 2/6
Piloerection / 0 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6
100 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6
1000 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6
10000 / 1/6 / 2/6 / 2/6 / 1/6 / 0/6 / 0/6 / 2/6
Discolored (test article-like) stool / 0 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6
100 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6 / 0/6
1000 / 0/6 / 0/6 / 0/6 / 0/6 / 4/6 / 0/6 / 4/6
10000 / 0/6 / 0/6 / 0/6 / 6/6 / 6/6 / 0/6 / 6/6

n/n: Total number of abnormal or dead animals observed / Total number of animals examined n'/n': Number of abnormal or dead animals observed / Number of animals that survived the study period

Table 2. Mortality and clinical observations in female mice.

n/n: Total number of abnormal or dead animals observed / Total number of animals examined

n'/n': Number of abnormal or dead animals observed / Number of animals that survived the study period