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[Effects of vitamins deficiency on the cytochrome P450 inducibility in rats].

Abstract
The purpose of the study was to determine multi-vitamin deficiency effects on the inducibility of main isoforms of cytochrome P450 in the rat liver. The study was carried out on 4 groups of Wistar rats. Rats of the 1st and 3rd group received semi-synthetic diets containing adequate (100% of recommended vitamin level) level of vitamins, the 2nd and 4th--the semi-synthetic diet containing vitamins in the amount of 20% from adequate level. The duration of the experiment was 4 weeks. During the last week indole-3-carbinol (I-3-C) in dose of 20 mg/kg body weight was added to the diet of the 3rd and 4th group of rats. Vitamin E content in liver and blood serum declined by 59 and 34%, respectively in rats which were fed vitamin-deficient diet (2nd group); vitamin A level decreased by 5 times in the liver, but was not changed in blood serum. Multi-vitamin deficiency in the diet led to the increase in the liver ethoxyresorufin O-dealkylase (EROD) activity of CYP1A1, methoxyresorufin O-dealkylase (MROD) activity of CYP1A2 and testosteron 6beta-hydroxylase (6beta-TG) activity of CYP3A by 11, 80 and 53%, respectively, and gene expression of CYP1A1, CYP1A2, CYP3A and AhR by 8,5; 1,6; 2,4 and 3,6 fold. In rats fed diet with adequate levels of vitamins (3rd group) I-3-C increased activity of EROD and MROD by 4,4 and 5,5 fold, and the expression of CYP1A1, CYP1A2 and AhR genes by 148; 3 and 3,5 fold compared to the parameters of the 1st group (without I-3-C). Multi-vitamin deficiency increased I-3-C-related induction of EROD activity and expression of CYP1A1 and CYP1A2 genes, but decreased I-3-C-related induction of the MROD activity. Thus, 5-fold reducing of vitamin content in rat diet lead to significant changes in activity and inducibility of cytochrome P450 of CYP1A and 3A family, which play a key role in the detoxification and metabolism of drugs.
AuthorsN V Trusov, G V Guseva, N A Beketova, I V Aksenov, L I Avrent'eva, L V Kravchenko
JournalVoprosy pitaniia (Vopr Pitan) Vol. 83 Issue 3 Pg. 4-11 ( 2014) ISSN: 0042-8833 [Print] Russia (Federation)
PMID25300103 (Publication Type: English Abstract, Journal Article)
Chemical References
  • Cytochrome P-450 Enzyme System
Topics
  • Animals
  • Avitaminosis (enzymology, pathology)
  • Cytochrome P-450 Enzyme System (biosynthesis)
  • Enzyme Induction
  • Liver (enzymology, pathology)
  • Male
  • Rats
  • Rats, Wistar

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