| Project/Area Number |
60470127
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用生物化学・栄養化学
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| Research Institution | Nagoya University |
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Principal Investigator |
YOSHIDA Akira Professor. School of Agriculture, Nagoya University, 農学部, 教授 (70035377)
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| Co-Investigator(Kenkyū-buntansha) |
HORIO Fumihiko Res. Associate. School of Agriculture, Nagoya University, 農学部, 助手 (20165591)
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| Project Period (FY) |
1985 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1985: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | xenobiotics / ascorbic acid(vitamin C) / vitamin E / lipid peroxidation / 過酸化脂質 / コレステロール / アスコルビン酸(ビタミンC) / カテコラミン / チロシン / PCB |
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| Research Abstract |
In our industrialized society, we have many chances to take xenobiotics as environmental chemicals, food additives or as medical drugs. Low molecular fat soluble xenobiotics are maily metabolized in liver microsomal mixed function oxidase system, and sometimes show quite similar metabolic effects although their chemical structures are different. In the present project, we found these xenobiotics induce hypercholesterolemia, increase the requirement of some vitamins such as ascorbic acid, vitamin E and A. When rats were fed diets containing PCB, DDT or other xenobiotics, serum levels of cholesterol were significantly elevated. Incorporation of^3H_2O into liver cholesterol, was increased and the activity of hepatic HMC-CoA reductase which is the rate limiting enzyme of cholesterol synthesis was induced by feeding xenobiotics. These results indicate the hypercholesterolemia by dietary xenobiotics is mainly due to the increased synthesis of liver cholesterol. This hypercholesterolemia was accompanied by the increased excretion of urinary catecholamines and <alpha>-blocker suppressed the hypercholesterolemia indicating the involvement of catecholamine in this type of hypercholesterolemia.
Feeding of xenobiotics accelerated the synthesis of ascorbic acid (Vitamin C) in rats and increased the vitamin C requirement in guinea pigs and in a rat mutant unable to synthesize ascorbic acid for maximum induction of hepatic mixed function oxidases. Xenobiotics accelerated the lipid peroxidation in the body and vitamin E and vitamin C were effective to prevent the increment of lipid peroxidation. Platelet aggregation was also stimulated by PCB or DDT probably due to the increased production of thromboxane A_2. In diabetic rats or spontaneously hypertensive rat(SHR), the loss of urinary vitamin C due to xenobiotics was much exergerated than that in normal rats.
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