Hepatic expression of cytochrome P450 in Zucker diabetic fatty rats

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Title
Hepatic expression of cytochrome P450 in Zucker diabetic fatty rats
Author(s)
S Y Park; C H Kim; J Y Lee; J S Jeon; Min Ju Kim; Song Hee Chae; Hyoung-Chin Kim; Soo Jin Oh; S K Kim
Bibliographic Citation
Food and Chemical Toxicology, vol. 96, pp. 244-253
Publication Year
2016
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.
Keyword
Cytochrome P450DiabetesHepatic metabolismInsulin resistanceZDF rat
ISSN
0278-6915
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.fct.2016.08.010
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
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