Liver enzyme activities after multiple administration of nifedipine in mice.
The effect of multiple nifedipine administration on hexobarbital sleeping time, liver monooxygenase and synthetase activities, lipid peroxidation and microsomal membrane fluidity were studied in male albino mice. The drug was administered orally at a dose of 25 mg/kg daily for 14 and 21 days. Nifedipine caused enzyme induction, demonstrated by shortened hexobarbital sleeping time, enhanced ethylmorphine N-demethylase, aniline 4-hydroxylase, ethoxycoumarine O-deethylase, UDP-glucuronyl transferase, glutathione S-transferase and NADPH-cytochrome c reductase activities and increased content of cytochrome P450 and cytochrome b5. This effect persisted until the 7th day after the last dose of nifedipine. There were no changes in lipid peroxidation and fluidity of the microsomal membranes after 14-day nifedipine administration. The increased cytochrome P450 content and drug metabolizing enzyme activities could be not associated with changes in these liver microsomal membrane properties.
Dimova
S
S
Department of Drug Toxicology, Bulgarian Academy of Sciences, Sofia.
Koleva
M
M
Rangelova
D
D
Stoytchev
T
T
D000284:Administration, Oral; D000818:Animals; D004790:Enzyme Induction; D006591:Hexobarbital / Q000494:pharmacology; D008025:Ligases / Q000096:biosynthesis*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D013250:Steroid Hydroxylases / Q000096:biosynthesis*
D006591:Hexobarbital; D013250:Steroid Hydroxylases; D008025:Ligases; D009543:Nifedipine