Age-related changes in hepatic expression and activity of cytochrome P450 in male rats.
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.
College of Pharmacy and RCTCP, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejeon, 305-764, Republic of Korea.
Kang Uk
KU
Yun
Soo Jin
SJ
Oh
Jung Min
JM
Oh
Keon Wook
KW
Kang
Chang-Seon
CS
Myung
Gyu Yong
GY
Song
Bong-Hee
BH
Kim
Sang Kyum
SK
Kim
D000375:Aging / Q000502:physiology*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D000072467:Cytochrome P450 Family 2; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D039181:Steroid 16-alpha-Hydroxylase / Q000096:biosynthesis / Q000378:metabolism
D007527:Isoenzymes; D008565:Membrane Proteins; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; C465260:Cyp3a2 protein, rat; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D019362:Cytochrome P-450 CYP2B1; D051544:Cytochrome P-450 CYP3A; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase