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. 2012 Jul;51(1):50-4.
doi: 10.3164/jcbn.11-79. Epub 2012 Mar 30.

Alteration of drug metabolizing enzymes in sulphite oxidase deficiency

Begum Tutuncu  1 , Vural Kuçukatay, Sevki Arslan, Barbaros Sahin, Asli Semiz, Alaattin Sen
Affiliations

Alteration of drug metabolizing enzymes in sulphite oxidase deficiency

Begum Tutuncu et al. J Clin Biochem Nutr. 2012 Jul.

Abstract

The aim of this study was to investigate the possible effects of sulphite oxidase (SOX, E.C. 1.8.3.1) deficiency on xenobiotic metabolism. For this purpose, SOX deficiency was produced in rats by the administration of a low molybdenum diet with concurrent addition of 200 ppm tungsten to their drinking water. First, hepatic SOX activity in deficient groups was measured to confirm SOX deficiency. Then, aminopyrine N-demethylase, aniline 4-hydroxylase, aromatase, caffeine N-demethylase, cytochrome b5 reductase, erythromycin N-demethylase, ethoxyresorufin O-deethylase, glutathione S-transferase, N-nitrosodimethylamine N-demethylase and penthoxyresorufin O-deethylase activities were determined to follow changes in the activity of drug metabolizing enzymes in SOX-deficient rats. Our results clearly demonstrated that SOX deficiency significantly elevated A4H, caffeine N-demethylase, erythromycin N-demethylase and N-nitrosodimethylamine N-demethylase activities while decreasing ethoxyresorufin O-deethylase and aromatase activities. These alterations in drug metabolizing enzymes can contribute to the varying susceptibility and response of sulphite-sensitive individuals to different drugs and/or therapeutics used for treatments.

Keywords: cytochrome P450s; drug metabolizing enzymes; rat; sulphite oxidase deficiency; sulphite sensitivity.

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Figures

Fig. 1
Fig. 1
The expression level of CYP1A1, CYP2B1, CYP2C6, CYP2E1 and CYP3A1 proteins in control rats and SOX-deficient rats. Treatments were carried out as described in Materials and Methods (a–e). Representative immunoblot analysis of liver microsomal CYP1A1, CYP2B1, CYP2C6, CYP2E1 and CYP3A1 proteins in experimental groups with rabbit anti-rat CYP1A1, CYP2B1, CYP2C6, CYP2E1 and CYP3A1 IgG. Lane 1–2, control; lane 3–5, SOX-deficiency. (f) Comparison of the CYPs protein levels among experimental groups. The bar graphs represent the mean intensity of the bands obtained from Western blot results. Experiments were repeated at least 3 times. Results are presented as the mean ± SD. *p<0.05, **p<0.01, ***p<0.001
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