Effects of a new neuroprotective agent KR-31378 on liver cytochrome P450s in male Sprague Dawley rats

Arch Pharm Res. 2003 Oct;26(10):800-4. doi: 10.1007/BF02980023.

Abstract

The effects of KR-31378, a neuroprotective agent for ischemia-reperfusion damage, on liver microsomal cytochrome P450s (CYPs) were investigated in male Sprague Dawley rats. When rats were treated orally with KR-31378 for 7 consecutive days, CYP3A-selective erythromycin N-demethylase (ERDM) activity was significantly induced in a dose-dependent manner. In Western immunoblotting, CYP 3A proteins were clearly induced by treatment with KR-31378. Within 24 h after treatment with 80 mg/kg of KR-31378, ERDM activity was induced in liver microsomes in accompanied by induction of the level of CYP 3A proteins. The present results suggest that KR-31378 might modulate the expression of CYP 3A enzymes in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Aryl Hydrocarbon Hydroxylases / biosynthesis
  • Blotting, Western
  • Cytochrome P-450 CYP1A1 / biosynthesis
  • Cytochrome P-450 CYP2B1 / biosynthesis
  • Cytochrome P-450 CYP2E1 / biosynthesis
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Cytochrome P-450 Enzyme System / drug effects
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Electrophoresis, Polyacrylamide Gel
  • Guanidines / administration & dosage
  • Guanidines / metabolism
  • Guanidines / pharmacokinetics*
  • Male
  • Microsomes, Liver / drug effects*
  • Microsomes, Liver / enzymology*
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / pharmacology*
  • Oxidoreductases, N-Demethylating / biosynthesis
  • Pyrans / administration & dosage
  • Pyrans / metabolism
  • Pyrans / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Guanidines
  • N''-cyano-N-(6-amino-3,4-dihydro-3-hydroxy-2-methyl-2-dimethoxymethyl-2H-benzopyran-4-yl)-N'-benzylguanidine
  • Neuroprotective Agents
  • Pyrans
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP2E1
  • Aryl Hydrocarbon Hydroxylases
  • CYP3A protein, human
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP2B1
  • Cytochrome P-450 CYP3A
  • Oxidoreductases, N-Demethylating