EurekaMag.com logo
+ Site Statistics
References:
52,725,316
Abstracts:
28,411,598
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

Effects of model traumatic injury on hepatic drug metabolism in the rat 3. differential responses of cytochrome p 450 subpopulations


Drug Metabolism and Disposition 12(5): 588-595
Effects of model traumatic injury on hepatic drug metabolism in the rat 3. differential responses of cytochrome p 450 subpopulations
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. 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 [high-performance liquid chromatography] 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.


Accession: 005314633



Related references

Effects of model traumatic injury on hepatic drug metabolism in the rat. III. Differential responses of cytochrome P-450 subpopulations. Drug Metabolism and Disposition: the Biological Fate of Chemicals 12(5): 588-595, 1984

Differential effects of traumatic brain injury on the cytochrome p450 system: a perspective into hepatic and renal drug metabolism. Journal of Neurotrauma 20(12): 1339-1350, 2004

Effects of model traumatic injury on hepatic drug metabolism in the rat. I. In vivo antipyrine metabolism. Drug Metabolism and Disposition: the Biological Fate of Chemicals 11(6): 517-525, 1983

Effects of model traumatic injury on hepatic drug metabolism in the rat 1. in vivo antipyrine metabolism. Drug Metabolism and Disposition 11(6): 517-525, 1983

Effects of model traumatic injury on hepatic drug metabolism in the rat 2. in vivo metabolism of hexobarbital and zoxazolamine. Drug Metabolism and Disposition 12(5): 582-587, 1984

Effects of model traumatic injury on hepatic drug metabolism in the rat. II. In vivo metabolism of hexobarbital and zoxazolamine. Drug Metabolism and Disposition: the Biological Fate of Chemicals 12(5): 582-587, 1984

Effects of model traumatic injury on hepatic drug metabolism in the rat. IV. Glucuronidation. Drug Metabolism and Disposition: the Biological Fate of Chemicals 13(4): 391-397, 1985

Effects of model traumatic injury on hepatic drug metabolism in the rat 4. glucuronidation. Drug Metabolism and Disposition 13(4): 391-397, 1985

Effects of model traumatic injury on hepatic drug metabolism in the rat. V. Sulfation and acetylation. Drug Metabolism and Disposition: the Biological Fate of Chemicals 13(4): 398-405, 1985

Effects of model traumatic injury on hepatic drug metabolism in the rat 5. sulfation and acetylation. Drug Metabolism and Disposition 13(4): 398-405, 1985