Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats

Yoshihiro NISHIYAMA; Shouta M.M. NAKAYAMA; Kensuke P. WATANABE; Yusuke K. KAWAI; Marumi OHNO; Yoshinori IKENAKA; Mayumi ISHIZUKA

doi:10.1292/jvms.15-0299

Toxicology

Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats

Yoshihiro NISHIYAMA, Shouta M.M. NAKAYAMA, Kensuke P. WATANABE, Yusuke K. KAWAI, Marumi OHNO, Yoshinori IKENAKA, Mayumi ISHIZUKA

Author information

Yoshihiro NISHIYAMA
Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, 18 W9, Kita-ku, Sapporo 060–0818, Japan
Shouta M.M. NAKAYAMA
Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, 18 W9, Kita-ku, Sapporo 060–0818, Japan
Kensuke P. WATANABE
Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, 18 W9, Kita-ku, Sapporo 060–0818, Japan
Yusuke K. KAWAI
Diagnostic Center for Animal Health and Food Safety, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080–8555, Japan
Marumi OHNO
Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, 18 W9, Kita-ku, Sapporo 060–0818, Japan
Yoshinori IKENAKA
Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, 18 W9, Kita-ku, Sapporo 060–0818, Japan
Water Research Group, Unit for Environmental Sciences and Management, North-West University, Potchefstroom, South Africa
Mayumi ISHIZUKA
Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, 18 W9, Kita-ku, Sapporo 060–0818, Japan

Keywords: cytochrome P450, metabolism, Rattus norvegicus, regulation, strain difference

JOURNAL FREE ACCESS

2016 Volume 78 Issue 4 Pages 675-680

DOI https://doi.org/10.1292/jvms.15-0299

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Abstract

Rat cytochrome P450 (CYP) exhibits inter-strain differences, but their analysis has been scattered across studies under different conditions. To identify these strain differences in CYP more comprehensively, mRNA expression, protein expression and metabolic activity among Wistar (WI), Sprague Dawley (SD), Dark Agouti (DA) and Brown Norway (BN) rats were compared. The mRNA level and enzymatic activity of CYP1A1 were highest in SD rats. The rank order of Cyp3a2 mRNA expression mirrored its protein expression, i.e., DA>BN>SD>WI, and was similar to the CYP3A2-dependent warfarin metabolic activity, i.e., DA>SD>BN>WI. These results suggest that the strain differences in CYP3A2 enzymatic activity are caused by differences in mRNA expression. Cyp2b1 mRNA levels, which were higher in DA rats, did not correlate with its protein expression or enzymatic activity. This suggests that the strain differences in enzymatic activity are not related to Cyp2b1 mRNA expression. In conclusion, WI rats tended to have the lowest CYP1A1, 2B1 and 3A2 mRNA expression, protein expression and enzymatic activity among the strains. In addition, SD rats had the highest CYP1A1 mRNA expression and activity, while DA rats had higher CYP2B1 and CYP3A2 mRNA and protein expression. These inter-strain differences in CYP could influence pharmacokinetic considerations in preclinical toxicological studies.

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