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Differential effects of diabetes on CYP2E1 and CYP2B4 proteins and associated drug metabolizing enzyme activities in rabbit liver

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Abstract

The effects of diabetes on cytochrome P450 (CYP)-dependent drug metabolizing enzymes are yet to be clarified. The most widely used animals in these studies have been rats, and information on the effects of diabetes on rabbit liver drug metabolizing enzymes have been unavailable until now. In this study, for the first time, a significant induction of liver CYP2E1 is demonstrated via immunoblot analysis in alloxan-induced rabbits. The CYP2E1 content of diabetic microsomes was highly correlated with the activities of liver aniline 4-hydroxylase (r=0.82, p<0.05), and p-nitrophenol hydroxylase (r=0.86, p<0.01), and diabetes increased the activities of the enzymes associated with CYP2E1. The activities of aniline 4-hydroxylase and p-nitrophenol hydroxylase were significantly increased by 1.7 and 1.8-fold, respectively compared to those of control rabbits. In marked contrast, diabetes had no effect on the protein levels of CYP2B4 as determined by immunoblotting and on benzphetamine N-demethylase activity, which is known to be specifically metabolized by CYP2B4 in rabbit liver. The present study demonstrates that diabetes increases the activities of CYP2E1 and associated enzymes but does not change the activity levels of CYP2B4 and associated enzymes in diabetic rabbits. These findings are in contrast to those of mice, hamsters and rats, and that suggest the presence of species-dependent responses of CYP-dependent drug metabolizing enzymes to diabetes.

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Acknowledgments

This study was supported in part by Turkish Academy of Sciences (TüBA) and Middle East Technical University Research Project Fund (Project No.: BAP-2002-01-08-01). The authors thank to Middle East Technical University Health Center for the analysis of blood constituents.

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  1. Department of Biological Sciences, Biochemistry Graduate Programme, Middle East Technical University, 06531, Ankara, Turkey

    Emel Arınç, Şevki Arslan & Orhan Adalı

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  1. Emel Arınç
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  2. Åževki Arslan
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  3. Orhan Adalı
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Correspondence to Emel Arınç.

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An account of this work was presented at the 19th European Workshop on Drug Metabolism, DMW-2004, in Antalya, Turkey, on 3–8 October 2004

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Arınç, E., Arslan, Ş. & Adalı, O. Differential effects of diabetes on CYP2E1 and CYP2B4 proteins and associated drug metabolizing enzyme activities in rabbit liver. Arch Toxicol 79, 427–433 (2005). https://doi.org/10.1007/s00204-005-0654-8

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