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1.
Bull Exp Biol Med. 2010 Aug;149(2):213-8.

Effects of combined treatment with resveratrol and indole-3-carbinol.

[Article in English, Russian]

Author information

1
Institute of Nutrition, Russian Academy of Medical Sciences, Moscow, Russia. nikkitosu@yandex.ru

Abstract

Male Wistar rats received a semisynthetic diet with resveratrol (100 mg/kg), indole-3-carbinol (20 mg/kg), or a mixture of these compounds in the same doses for 1 week. Activities of ethoxyresorufin dealkylase (EROD), methoxyresorufin dealkylase (MROD), pentoxyresorufin dealkylase (PROD), and 6β-testosterone hydroxylase (6β-TH) and the content of mRNA for CYP1A1, CYP1A2, and CYP3A1 were elevated in the liver of rats receiving indole-3-carbinol. These changes were accompanied by an increase in activity of phase II xenobiotic metabolism enzymes (quinone reductase, hemoxygenase-1, glutathione transferase, and UDP glucuronosyl transferase). Resveratrol did not modify activity of these enzymes. After combined treatment with the test compounds, resveratrol suppressed the indole-3-carbinol-induced increase in activities of EROD, MROD, PROD, and 6β-TH, and expression of the corresponding genes. Combined treatment was characterized by potentiation of the antioxidant effects of these compounds.

PMID:
21113494
DOI:
10.1007/s10517-010-0910-7
[Indexed for MEDLINE]
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2.
Bull Exp Biol Med. 2012 Dec;154(2):250-4.

Indole-3-carbinol induction of CYP1A1, CYP1A2, and CYP3A1 activity and gene expression in rat liver under conditions of different fat content in the diet.

Author information

1
Institute of Nutrition, Russian Academy of Medical Sciences, Moscow, Russia.

Abstract

Wistar male rats were fed semisynthetic diet with different fat content for 6 weeks: fat-free, 10%, and 30% fat (sunflower oil and lard, 1:1). Increasing fat content was associated with an increase in ethoxyresofurin-O-dealkylase (EROD) activity of CYP1A1, methoxyresofurin-O-dealkylase (MROD) activity of CYP1A2, and 6β-testosterone-hydroxylase (6β-TH) activity of CYP3A1. EROD, MROD, and 6β-TH activities in rats on high-fat diet exceeded those in rats on fat-free diet by 64, 58, and 140%, respectively. Addition of indole-3-carbinol to the diet led to an increase in CYP1A1, CYP1A2, and CYP3A1 activities and mRNA levels, the degree of this increase was lower with increasing fat content in the diet. In rats on fat-free, 10% fat, and 30% fat diets, indole-3-carbinol induced EROD activity by 4.7, 3.2, and 2.0 times, respectively; MROD activity by 5.9, 5.6, and 5.4 times; and 6β-TH activity by 2.1, 1.9, and 1.3 times. A correlation was detected between activities of the studied cytochrome P-450 isoforms, their inducibility by indole-3-carbinol, and vitamin A and E levels in rat liver.

PMID:
23330137
DOI:
10.1007/s10517-012-1924-0
[Indexed for MEDLINE]
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3.
Nutr Cancer. 2000;36(1):112-21.

N-methoxyindole-3-carbinol is a more efficient inducer of cytochrome P-450 1A1 in cultured cells than indol-3-carbinol.

Author information

1
Department of Life Sciences and Chemistry, Roskilde University, Denmark.

Abstract

The well-documented reduction of cancer risk by high dietary cruciferous vegetable intake may in part be caused by modulation of cytochrome P-450 (CYP) expression and activity by indoles. The purpose of the present experiments was to study the mechanism of CYP 1A1 induction by N-methoxyindole-3-carbinol (NI3C) in cultured cells and to compare the CYP-inducing potential of NI3C and indole-3-carbinol (I3C) administered to rats. NI3C induced 7-ethoxyresorufin-O-deethylase (EROD) activity in Hepa-1c1c7 cells in a concentration-dependent manner with 10-fold higher efficiency than I3C. Inasmuch as NI3C induced binding of the aryl hydrocarbon receptor (AhR) to the dioxin-responsive element and induced expression of endogenous CYP 1A1 mRNA and an AhR-responsive chloramphenicol acetyl transferase construct, we conclude that NI3C can activate the AhR. Besides the induction of CYP 1A1, we observed an inhibition of EROD activity, with a concentration causing 50% inhibition of 6 microM. Oral administration of NI3C at 570 mumol/kg body wt to male Wistar rats increased the hepatic CYP 1A1 and 1A2 protein levels, as well as the EROD and 7-methoxyresorufin O-demethylase activities at 8 and 24 hours after administration, but the responses were less pronounced than after administration of I3C at 570 mumol/kg body wt. Furthermore, NI3C did not induce hepatic 7-pentoxyresorufin O-depentylase activity, as I3C did. Ascorbigen, another indolylic compound formed during degradation of glucobrassicin in the presence of ascorbic acid, was tested in the same animal model, and ascorbigen only weakly induced hepatic CYP 1A1 and 1A2, but not CYP 2B1/2. In conclusion, NI3C is a more efficient inducer of CYP 1A1 in cultured cells than I3C but is less active when administered to rodents.

PMID:
10798223
DOI:
10.1207/S15327914NC3601_15
[Indexed for MEDLINE]

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