TABLE 1

Effect of carbon monoxide on P450R activity and doxorubicin reduction in rat and human liver microsomes P450R activity was determined spectrophotometrically as the rate of cytochrome c reduction. Doxorubicin reduction was assayed spectrophotometrically as the rate of doxorubicin-stimulated microsomal NADPH consumption. Rat liver microsomes were prepared from untreated adult male Fischer 344 rats. Human liver microsome sample K15, from a tissue bank maintained by Dr. Tadanobu Inaba (University of Toronto, Toronto, ON, Canada), was used in this experiment. Data are expressed as mean ± S.D. of triplicate or sextuplicate determinations.


Sample

P450R Activity

Doxorubicin Reduction
nmol/min/mg microsomal protein
Rat liver microsomes
   – Carbon monoxide 253 ± 13 11.0 ± 0.4
   + Carbon monoxide 274 ± 3 7.0 ± 0.8**
Human liver microsomes
   – Carbon monoxide 103 ± 2 4.8 ± 0.3
   + Carbon monoxide
101 ± 9
6.1 ± 0.7**
  • ** Significantly different (p ≤ 0.01) from activity in the absence of carbon monoxide, based on Student's t test