PT  - JOURNAL ARTICLE
AU  - L K Griffeth
AU  - G M Rosen
AU  - E J Rauckman
TI  - Effects of model traumatic injury on hepatic drug metabolism in the rat. III. Differential responses of cytochrome P-450 subpopulations.
DP  - 1984 Sep 01
TA  - Drug Metabolism and Disposition
PG  - 588--595
VI  - 12
IP  - 5
4099  - http://dmd.aspetjournals.org/content/12/5/588.short
4100  - http://dmd.aspetjournals.org/content/12/5/588.full
SO  - Drug Metab Dispos1984 Sep 01; 12
AB  - A previously validated small mammal trauma model, hind-limb ischemia secondary to infrarenal aortic ligation in the rat, was utilized to further investigate the effects of traumatic injury on the hepatic cytochromes P-450. In vitro drug metabolism studies with hexobarbital and zoxazolamine as substrates confirmed the post-traumatic depression of the cytochrome P-450-catalyzed oxidation of these drugs which was suggested by previous in vivo pharmacokinetic studies. Enzyme kinetic studies revealed diminished Vmax values with no change in Km, a finding which would seem to concur with the previously demonstrated decrease in hepatic cytochrome P-450 content after model trauma. Moreover, a battery of in vitro microsomal monooxygenase assays demonstrated that model trauma exerted a differential effect on various hepatic cytochrome P-450 isoenzymes. This phenomenon was confirmed by anion-exchange HPLC of solubilized hepatic microsomal hemoproteins. One of the most interesting aspects of this selective effect on cytochrome P-450 subtypes was the relative induction of cytochrome P-448 content and activity, in contrast to the variable decrease seen with cytochrome P-450 activities. The potential in vivo sequelae of this differential influence were suggested by changes observed in the urinary metabolic profile of antipyrine after model trauma.