Age-related changes in hepatic expression and activity of cytochrome P450 in male rats

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Title
Age-related changes in hepatic expression and activity of cytochrome P450 in male rats
Author(s)
K U Yun; Soo Jin Oh; J M Oh; K W Kang; C S Myung; G Y Song; B H Kim; S K Kim
Bibliographic Citation
Archives of Toxicology, vol. 84, no. 12, pp. 939-946
Publication Year
2010
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 b5 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.
Keyword
Cytochrome P450Development and agingDrug-metabolizing enzymeExpression and activityLiver
ISSN
0340-5761
Publisher
Springer
DOI
http://dx.doi.org/10.1007/s00204-010-0520-1
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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