Characteristics of coumarin metabolism by liver microsomes from cobalt-pretreated mice

1. Cobalt pretreatment of male mice leads to increased liver microsomal mixed-function oxidation of various coumarin derivatives; 7-ethoxycoumarin, 7-hydroxycoumarin and coumarin are metabolized three to four times more rapidly than in control microsomes.

2. In Arrhenius plots of 7-ethoxycoumarin de-ethylation, the temperature at which phase transition occurs is not changed by cobalt pretreatment. However, at high temperature, above the transition point, the slope indicates that cobalt lowers the apparent activation energy of the reaction to 65% of control value.

3. Metabolism of 7-hydroxycoumarin by hepatic microsomes from cobalt-treated mice gave 3,7-, 6,7- and 7,8-dihydroxycoumarin, identified by g.l.c. and mass spectrometry.