title: Hepatic expression of cytochrome P450 in Zucker diabetic fatty rats.
abstract: In this study, the hepatic expression of cytochrome P450 (CYP) enzymes, including CYP1A1/2, 2B1, 2C11, 2E1, 3A1/2, and 4A, was investigated in 5-week-old (insulinresistant state) and 11-week-old (diabetic) Zucker diabetic fatty (ZDF) rats. Serum glucose and glycated hemoglobin levels were increased in 11-week-old ZDF rats, but not in 5-weekold ZDF rats. Hyperinsulinemia was observed in both age groups. The microsomal protein, total CYP, CYP reductase, CYP1A1/2, and CYP3A1 levels did not differ between 5- and 11-week-old ZDF rats and their respective control rats, while CYP4A was up-regulated in both groups. Hepatic levels of cytochrome b5, CYP2B1, CYP2C11, CYP2E1, and CYP3A2 were decreased in 5-week-old ZDF rats, but not in 11-week-old ZDF rats. Similarly, pentoxyresorufin O-depentylase, testosterone 2α- and 16α-hydroxylase, chlorzoxazone 6- hydroxylase, and midazolam 1'- and 4-hydroxylase activities were decreased only in 5-weekold ZDF rats. Based on these results, the 5-week-old ZDF rats exhibited down-regulation of the major CYP enzymes. These results suggest that hepatic expression of CYP enzymes may be dysregulated during development in ZDF rats. With the exception of CYP2B1 and CYP4A, the hepatic levels and activities of CYP were comparable between 11-week-old ZDF and control rats, suggesting that xenobiotic metabolism is normally regulated in the early diabetic state.
authors: College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea.
authors: So Young
authors: SY
authors: Park
authors: College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea.
authors: Chung Hyeon
authors: CH
authors: Kim
authors: College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea.
authors: Ji Yoon
authors: JY
authors: Lee
authors: College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea.
authors: Jang Su
authors: JS
authors: Jeon
authors: Bio-Evaluation Center, KRIBB, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungcheongbuk-do, 28116, Republic of Korea.
authors: Min Ju
authors: MJ
authors: Kim
authors: Bio-Evaluation Center, KRIBB, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungcheongbuk-do, 28116, Republic of Korea.
authors: Song Hee
authors: SH
authors: Chae
authors: Bio-Evaluation Center, KRIBB, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungcheongbuk-do, 28116, Republic of Korea.
authors: Hyoung Chin
authors: HC
authors: Kim
authors: Bio-Evaluation Center, KRIBB, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungcheongbuk-do, 28116, Republic of Korea. Electronic address: diatree@kribb.re.kr.
authors: Soo Jin
authors: SJ
authors: Oh
authors: College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea. Electronic address: sangkim@cnu.ac.kr.
authors: Sang Kyum
authors: SK
authors: Kim
mesh_terms: D000367:Age Factors; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015151:Immunoblotting; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D011924:Rats, Zucker
chemical_list: D003577:Cytochrome P-450 Enzyme System
keywords: Cytochrome P450; Diabetes; Hepatic metabolism; Insulin resistance; ZDF rat