First evidence of cytochrome P-450 induction in the mouse brain by phenytoin.
Long-term administration of phenytoin (60 mg/kg) to male C57Bl/6J mice causes an average drug serum level of 16-19 micrograms/ml. Cytological changes consisting of focal axonal swellings in the deep cerebellar nuclei are characterized by an increasing accumulation of vesiculotubular membranes in the dense, but ribosome-deficient axoplasm. Microsomal fractions of brain and liver were prepared at intervals until the 80th day of treatment to determine their cytochrome P-450 activities and isoenzyme characteristics. The cerebellar tissue was shown to be distinguished by a 15-fold enhancement of cytochrome P-450 PB3a activity, that means twice the extent of that found in liver and cerebrum.
Volk
B
B
Abt. Neuropathologie, Universität Freiburg, F.R.G.
Amelizad
Z
Z
Anagnostopoulos
J
J
Knoth
R
R
Oesch
F
F
D000818:Animals; D001921:Brain / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D002529:Cerebellar Nuclei / Q000378:metabolism / Q000648:ultrastructure; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010672:Phenytoin / Q000493:pharmacokinetics / Q000494:pharmacology*
D010672:Phenytoin; D003577:Cytochrome P-450 Enzyme System