TABLE 1

Pyrazole increases hepatic CYP2A5 levels, serum ALT, and hepatic oxidative damage in vivo

Values represent fold increases in expression relative to untreated controls (n = 3). Means that are not significantly different are denoted by a common letter designation, whereas means with different letter designations are significantly different (p < 0.05) as determined by analysis of variance.

CYP2A5 mRNA
CYP2A5 Protein
COH Activity
ALT
Protein Carbonyl Formation
Dose* (mg/kg)
    0 1.0 ± 0.1a 1.0 ± 0.1a 1.0 ± 0.1a 1.0 ± 0.1a 1.0 ± 0.1a
    50 3.1 ± 1.2b 3.0 ± 0.4b 5.5 ± 0.9b 2.1 ± 0.7a 0.9 ± 0.0a
    100 5.4 ± 0.8c 4.3 ± 0.4c 8.7 ± 1.0b 2.7 ± 0.5a 1.1 ± 0.3a
    200 7.3 ± 0.5c 5.8 ± 0.4d 13.6 ± 1.5c 18.9 ± 6.9b 1.7 ± 0.1b
Time† (h)
    0 1.0 ± 0.1a 1.0 ± 0.2a 1.0 ± 0.1a 1.0 ± 0.1a 1.0 ± 0.1a
    12 2.2 ± 0.7a 1.7 ± 0.6a 1.5 ± 0.4b 4.5 ± 1.6a 1.0 ± 0.1a
    24 4.9 ± 0.7b 4.2 ± 0.6b 7.3 ± 1.1c 10.7 ± 2.8a 1.4 ± 0.1a,b,c
    48 4.5 ± 0.9b 5.7 ± 0.7b 10.6 ± 2.3c,d 20.3 ± 6.8b 1.5 ± 0.3b,c
    72
7.3 ± 0.5c
5.8 ± 0.4c
13.6 ± 1.5d
18.9 ± 6.9b
1.7 ± 0.1c

  • ↵* Mice were euthanized 72 h after treatment with the indicated doses of pyrazole.

  • ↵† For time-course experiments, a dose of 200 mg/kg was used.