TABLE 1

In vitro sulfoxidation of ABZ and FBZ by cattle and sheep liver microsomes The involvement of the FMO and P450 systems was estimated by the difference between the sulfoxidation rates in control incubations and those observed after either inhibition or inactivation of FMO. Values are expressed in nmol · min-1 · mg-1 of microsomal protein. Data are the mean of 12 determinations.

Control
MTZ (100 μM)
Estimated Involvement
FMO
P450
Cattle
   ABZa
      (total) ABZSO 0.690 0.280*** 0.410 0.280
      (+) ABZSO 0.500 0.030*** 0.470 0.030
      (-) ABZSO 0.190 0.250 0.0 0.190-0.250
      ee (%) 100 78
   FBZa
      (total) OFZ 0.094 0.018*** 0.076 0.018
      (+) OFZ 0.072 0.004** 0.068 0.004
      (-) OFZ 0.022 0.014* 0.008 0.014
      ee (%) 79 56
Sheep
   ABZa
      (total) ABZSO 0.530 0.210*** 0.320 0.210
      (+) ABZSO 0.420 0.080*** 0.340 0.080
      (-) ABZSO 0.110 0.130 0.0 0.110-0.130
      ee (%) 100 24
   FBZb
      (total) OFZ 0.210 0.041*** 0.169 0.041
      (+) OFZ 0.160 0.020*** 0.140 0.020
      (-) OFZ 0.051 0.021*** 0.030 0.021
      ee (%)
65
2

  • ee, enantiomeric excess produced by the enzymatic system.

    Values are significantly different from control incubations at *p < 0.05. **p < 0.01, and ***p < 0.001.

  • ↵ a MTZ-treated liver microsomes were subjected to thermal treatment (2 min at 50°C) before the addition of the inhibitor (see Materials and Methods)

  • ↵ b Competitive inhibition of FMO was assessed by MTZ preincubation without thermal pretreatment (see Materials and Methods)