Ascorbic Acid Deficiency Reduces the Level of mRNA for Cytochrome P-450 on the Induction by Polychlorinated Biphenyls.

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概要

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• Ascorbic acid (ASA) deficiency causes a decrease in hepat-ic concentration of cytochrome P-450 and a decrease in hepatic activity of drug-metabolizing enzymes in rats unable to synthesize AsA (ODS rats). To study the mechanism of the decrease in hepatic concentration of cytochrome P-450 isozymes by AsA deficiency, we chose the xenobiotics-inducible cytochrome P-450 and performed the experiments indicated below. AsA-deficient rats were fed polychlorinated biphenyls (PCB) which markedly induce both CYP1A subfamily and several isozymes in CYP2B subfamily. First, we assayed the activities of two drug-metabolizing enzymes so that one could be functionally distinguished from another. AsA deficiency significantly reduced the hepatic activity of aminopyrine-N-demethylase in ODS rats with and without dietary PCB, but had no effect on benzo(a)pyrene hydroxylase activity. Secondly, quantitative immunoblot analyses demonstrated that the levels of CYP2B1/2B2 and CYP 1 A 1 in the AsA-deficiency rats fed PCB were approximately 60 and 80% lower than those found in rats fed AsA-supplemented diet. The degree of reduction in CYP2B1/2B2 was greater than CYP 1 A 1. Thirdly, AsA deficiency caused a decrease in hepatic abundance of CYP2B 1 /2B2 mRNA, whereas it had no effect on the levels of CYP 1 A 1 and 1A2 mRNA. These results indicated that dietary AsA selectively affects the levels of CYP2B 1 /2B2 mRNA among cytochrome P-450 induced by PCB and plays important roles for optimum induction of drug-inducible cytochrome P-450. We concluded that AsA deficiency decreases specific Proms of drug-inducible cytochrome P-450, especially CYP2B1/2B2 and that the reduction of CYP2B1/2B2 mRNA level in AsA-deficient rats caused a decrease in cytochrome P-450 concentration and hepatic activity of drug-metabolizing enzymes.

• 財団法人 学会誌刊行センターの論文

著者

• HORIO Fumihiko

  Loboratory of Nutritional Biochemistry, Department of Agricultural Chemistry, Nagoya University

• KOBAYASHI Tomoko

  Fuculty of Pharmaceutical Sciences, Nagoya City University

• ODA Hiroaki

  Loboratory of Nutritional Biochemistry, Department of Agricultural Chemistry, Nagoya University

• MATSUSHITA Natsuki

  Loboratory of Nutritional Biochemistry, Department of Agricultural Chemistry, Nagoya University

• YOSHIDA Akira

  Loboratory of Nutritional Biochemistry, Department of Agricultural Chemistry, Nagoya University

関連論文

• Ascorbic Acid Deficiency Reduces the Level of mRNA for Cytochrome P-450 on the Induction by Polychlorinated Biphenyls.

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