Changes in the Gene Expression and Enzyme Activity of Hepatic Cytochrome P450 in Juvenile Sprague-Dawley Rats

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概要

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• The developmental changes in the hepatic cytochrome P450 (CYP) content, mRNA expression of 12 hepatic CYP subtypes, and the enzyme activities of 5 hepatic CYP subfamilies in rats were investigated using non-treated male and female Sprague-Dawley rats of ages postnatal day (PD) 4, 16, and 30 and 8 and 12 weeks. The hepatic proliferation kinetics was also determined by using the phospho-histone H3 (p-histon)-labeled hepatocyte index. The developmental changes in the enzyme activities of hepatic expression of CYP1A and CYP3A in rats were similar to those in humans, although there is no fetal-neonatal dominant CYP3A subtype in rat livers unlike human CYP3A7. On the other hand, the developmental pattern of expression of the CYP2C subfamily differed between humans and rats. Enzyme activity and mRNA expression of each hepatic CYP subtype in rats on PD 30 was similar to that after 8 weeks of age, except in the case of sex-dependent CYP subtypes. The p-histon-labeled hepatocyte index was approximately 10-fold higher in PD 30 rats than in 8-week-old rats. Therefore, the livers of juvenile rats, which have high hepatocellular proliferation activity and a sufficient amount of metabolic enzymes such as CYP, may be more sensitive to the cytotoxic and carcinogenic effects of chemicals than the livers of adult rats. Thus, our results on developmental difference of hepatic CYPs in juvenile rats are useful to identify underlying age-dependent susceptibility of chemical-induced toxicity, and to understand developmental change of chemical disposition.

著者

• SAKAI Hiroki

  Laboratory of Oncological Pathology, Aichi Cancer Center Research Institute

• SASAKI Jun

  Department of Production Systems Engineering, Toyohashi University of Technology

• 坂井 宏明

  帯広畜産大学畜産学部獣医学科家畜内科学教室

• Sakai Hiroki

  Laboratory Of Biological Chemistry Department Of Chemistry Faculty Of Science Hokkaido University

• ASAOKA Yoshiji

  Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University

• GORYO Masanobu

  Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University

• YANAI Tokuma

  Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University

• MASEGI Toshiaki

  Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University

• OKADA Kouske

  Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University

• SAKAI Hiroki

  Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University

• SASAKI Jun

  Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University

• OKADA Kosuke

  Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University

• Sasaki Jun

  Department Of Internal Medicine Fukuoka University School Of Medicine

• Sasaki Jun

  Department Of Cardiovascular Surgery Sapporo Chuo Hospital

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