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Title 

Effects of age increase on hepatic expression and activity of cytochrome P450 in male C57BL/6 mice

Authors 

H C KwakHyoung-Chin KimSoo Jin OhS K Kim

Publisher 

Pharmaceutical Society of Korea

Issue Date 

2015

Citation 

Archives of Pharmacal Research, vol. 38, no. 5, pp. 857-864

Keywords 

AgingCytochrome P450Drug-metabolizing enzymeLiverMale mice

Abstract 

Effects of aging on hepatic expression and activity of cytochrome P450 (CYP) isoforms were investigated in male mice aged 2, 6, 18, and 30 months. Microsomal protein, total CYP, cytochrome b5 and NADPH-dependent cytochrome P450 reductase contents in liver were fully expressed in young (2-month-old) mice. Neither Cyp1a1 nor Cyp2c was detected in any aged mice. And Cyp1a2 was maximally expressed at 2 months and decreased with age. Hepatic levels of Cyp2b10 and Cyp3a11 were decreased in 30-month-old mice. Hepatic Cyp2e1 levels were constantly maintained from 2-month to 30-month old mice. Hepatic activities of ethoxyresorufin-O-deethylase and methoxyresorufin-O-demethylase were gradually decreased after 6 months. The 30-month-old mice exhibited the lowest activity of midazolam 1′-hydroxylase. Pentoxyresorufin-O-depenthylase activity was decreased in 30-month-old mice, but not statistically significant. There were no significant differences in hepatic activities of chlorzoxazone 6-hydroxylase and midazolam 4-hydroxylase. The present study shows that increasing age, especially 30-month-old mice, leads to decrease in expression and activity of hepatic CYP isoforms, suggesting that aging mice exhibit poor hepatic drug-metabolizing capacity.

ISSN 

0253-6269

Link 

http://dx.doi.org/10.1007/s12272-014-0452-z

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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