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.
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Acknowledgments
This work was supported by Engineering Research Center program (grant R11-2002-100-00000-0) and by Priority Research Centers Program (2009-0093815) through the Research Foundation of Korea (NRF) grant funded by the Korea Government (MEST).
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Yun, K.U., Oh, S.J., Oh, J.M. et al. Age-related changes in hepatic expression and activity of cytochrome P450 in male rats. Arch Toxicol 84, 939–946 (2010). https://doi.org/10.1007/s00204-010-0520-1
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DOI: https://doi.org/10.1007/s00204-010-0520-1