TABLE 2

Irreversibility of the inactivation of human liver microsomal POD activity by zileuton racemate

Data represent mean and S.D. of n = 3 determinations and are expressed as the percentage of control (solvent and NADPH only). Human liver microsomes were incubated in the presence and absence of zileuton (200 μM) for 20 min (see Materials and Methods). Some incubations contained GSH, catalase, or SOD. Dialysis was carried out at 4°C for 4 h, which was sufficient time to completely reverse the inhibitory effects of fluvoxamine (not a time-dependent inhibitor of CYP1A2).


Assay Component

Percentage of Control
Solvent plus NADPH 100
Zileuton minus NADPH 91.6 ± 6.17
Zileuton plus NADPH 49.9 ± 1.32
Zileuton plus NADPH and GSH (2 mM) 52.4 ± 1.89
Zileuton plus NADPH and catalase (500 units) 50.8 ± 4.01
Zileuton plus NADPH and SOD (500 units) 50.7 ± 3.00
Zileuton plus NADPH and dialysis 61.7 ± 1.17
Furafylline (10 μM) plus NADPH
22.6 ± 0.94