セレン欠乏がもたらすラット肝薬物代謝酵素系への影響

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Selenium (Se) is an essential trace element and plays many important biological roles in the body. Selenium deficiency is associated with Keshan disease in clinical cases. However, little has been reported on the relationship between selenium deficiency and drug-metabolizing enzyme activities other than reduced glutathione peroxidase (GPX) activity resulting in increased oxidative stress. In this study, we examined the effects of selenium deficiency on several drug-metabolizing enzymes in male Wistar rats. The contents of mRNA and protein of CYP2C11, which is a male specific P450 isoform, were significantly reduced in selenium deficiency. 17β-Hydroxysteroid dehydrogenase (17β-HSD), which has a stronger activity in male rather than female rats, showed also significantly decreased enzyme activity with lowering tendency toward a reduced mRNA level. Aldehyde oxidase (AO) activity was almost completely disappeared in selenium deficiency without an accompanying by the decrease of the mRNA level. Other enzymes such as CYP3A, CYP2A, CYP2B, carbonyl reductase, 3α-HSD, flavin-containing monooxygenase and 15-ketoprostaglandin 〓13-reductase were not affected in selenium deficiency. These results suggested that selenium deficiency might decrease the activity and mRNA level of CYP2C11 and 17β-HSD by impairing the testosterone-hypothalamus-pituitary axis, whereas AO was influenced by a different mechanism.
東北薬科大学の論文