Abstract
Age-related changes in hepatic expression and activity of cytochrome P450 (CYP) were investigated in male rats aged 3 (weanling), 12 (young), 26 (adult), and 104 (old) weeks. Levels of microsomal protein, total CYP, and cytochrome b(5) increased fully after puberty. CYP1A1 was detected only in 3-week-old rats, and CYP1A2, CYP2B1, and CYP2E1 were maximally expressed at 3 weeks but decreased at 12 and 26 weeks. CYP2C11 and CYP3A2 increased markedly after puberty and decreased with aging. Ethoxyresorufin-O-deethylase, methoxyresorufin-O-demethylase, pentoxyresorufin-O-depenthylase, and p-nitrophenol hydroxylase activities were at their highest in 3-week-old rats, and midazolam hydroxylase activity was at a maximum in 12-week-old rats but decreased with aging. The present results show that increasing age caused significant alterations in hepatic expression/activity of CYP isoforms in an isoform-specific manner. These results suggest that age-related changes in hepatic CYP isoforms may be an important factor for deciding the efficacy and safety of xenobiotics.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Aging / physiology*
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Animals
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Aryl Hydrocarbon Hydroxylases / biosynthesis
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Aryl Hydrocarbon Hydroxylases / metabolism
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Cytochrome P-450 CYP1A1 / biosynthesis
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Cytochrome P-450 CYP1A1 / metabolism
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Cytochrome P-450 CYP1A2 / biosynthesis
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Cytochrome P-450 CYP1A2 / metabolism
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Cytochrome P-450 CYP2B1 / biosynthesis
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Cytochrome P-450 CYP2B1 / metabolism
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Cytochrome P-450 CYP2E1 / biosynthesis
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Cytochrome P-450 CYP2E1 / metabolism
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Cytochrome P-450 CYP3A
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Cytochrome P-450 Enzyme System / biosynthesis
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Cytochrome P-450 Enzyme System / metabolism*
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Cytochrome P450 Family 2
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Isoenzymes / biosynthesis
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Isoenzymes / metabolism
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Liver / enzymology*
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Male
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Membrane Proteins / biosynthesis
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Membrane Proteins / metabolism
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Microsomes, Liver / enzymology
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Rats
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Rats, Sprague-Dawley
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Steroid 16-alpha-Hydroxylase / biosynthesis
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Steroid 16-alpha-Hydroxylase / metabolism
Substances
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Isoenzymes
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Membrane Proteins
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Cytochrome P-450 Enzyme System
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Cytochrome P-450 CYP2E1
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Aryl Hydrocarbon Hydroxylases
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CYP2C11 protein, rat
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Cyp3a2 protein, rat
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Cytochrome P-450 CYP1A1
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Cytochrome P-450 CYP1A2
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Cytochrome P-450 CYP2B1
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Cytochrome P-450 CYP3A
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Cytochrome P450 Family 2
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Steroid 16-alpha-Hydroxylase