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This version was published on 1 April 2009
Lab Anim 2009;43:205-211
doi:10.1258/la.2008.007146
© 2009 Laboratory Animals Limited

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Soft-hydrothermal processing of red cedar bedding reduces its induction of cytochrome P450 in mouse liver

Z Li 1, S Okano 2, K Yoshinari 3, T Miyamoto 2, Y Yamazoe 3, K Shinya 4, K Ioku 1 and N Kasai 2 

1 Graduate School of Environmental Studies; 2 Institute for Animal Experimentation, Graduate School of Medicine; 3 Graduate School of Pharmaceutical Sciences, Tohoku University, Japan; 4 International Center for Medical Research and Treatment, Graduate School of Medicine, Kobe University, Japan

Corresponding author: Noriyuki Kasai, Institute for Animal Experimentation, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. Email: nkasai{at}mail.tains.tohoku.ac.jp

Red cedar-derived bedding materials cause changes in cytochrome P450-dependent microsomal enzyme systems in laboratory animals. We examined the effect of essential oil of red cedar (EORC), as well as the effect of bedding from which it had been removed, on the hepatic expression cytochrome P450s in mice. EORC was obtained from liquid extracts of red cedar bedding by a soft-hydrothermal process and was administered orally to mice. Between days 1 and 2 after administration, hepatic P450s were significantly induced as follows: CYP3As, 7.1x; CYP1As, 1.6x; CYP2E1, 1.5x; CYP2Cs, 1.6x. A housing study of mice indicated that red cedar bedding increased the levels of these P450s in mouse liver, whereas mice housed in cedar bedding from which EORC had been removed (ST-cedar bedding) showed significantly lower levels of P450s, especially CYP3As, CYP1As and CYP2E1. Soft-hydrothermal processing partially removed many components of EORC. In particular, several volatile sesquiterpenes, naphthalene-derived aromatics and 4,4-dimethyl-13{alpha}-androst-5-ene were decreased in the ST-cedar bedding, suggesting that these may be responsible for P450 induction. This study demonstrated that the removal of these volatile compounds by soft-hydrothermal processing can decrease the hepatic P450-inducing effect of red cedar bedding.

Key Words: Red cedar bedding • essential oil • soft-hydrothermal processing • cytochrome P450 induction • mouse liver


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