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1994 | 41 | 3 |

Tytuł artykułu

Clofibrate and di[2-ethylhexyl]phthalate increase ubiquinone contents without affecting cholesterol levels

Warianty tytułu

Języki publikacji

EN

Abstrakty

Induction studies were performed on liver, muscle, heart, brain and blood by feeding Sprague-Dawley rats a diet containing a peroxisome proliferator, clofibrate or di(2-ethylhexyl)phthalate. Ingestion of these drugs resulted in an increase in the amount of two different types of ubiquinone homologues UQ9 and UQ10 found in rat. Phthalate proved to be the more effective drug, leading to a highly increased amount of ubiquinone in the liver. Increases were also found in all the above-mentioned organs except the brain. The UQ9 levels were raised to 400, 200,120 and 120%, of the respective normal values. The antioxidant and hypolipidemic agent, probucol, was used as a control to evaluate whether the increased ubiquinone level constituted a response to the elevated hydrogen peroxide pressure, resulting from the induced increase in fatly acid 0-oxidation. In the presence of probucol, ubiquinone levels were decreased in all the above-mentioned organs except heart and brain. Probucol had limited effects on the amount of cholesterol and did not significantly alter the amount of dolichol. The two peroxisome proliferators differed in their effects on cholesterol, as well as on dolichol levels which was induced by phthalate but not by clofibrate. The possible mechanisms involved, and the importance of low toxicity drugs which could elevate ubiquinone levels in various tissues, arc discussed.

Słowa kluczowe

Wydawca

-

Rocznik

Tom

41

Numer

3

Opis fizyczny

p.321-329,fig.

Twórcy

autor
  • University of Stockholm, S-106 91 Stockholm, Sweden

Bibliografia

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  • 2. Ramasarma, T. (1985) Natural occurrence and distribution of coenzyme Q; in Coenzyme Q, Biochemistry, Bioenergetics and Clinical Applications of Ubiquinone (Lenaz, G., ed.) pp. 67-81, John Wiley, New York.
  • 3. Ernster, L., Lee, I.-Y., Norling, B. & Persson, B. (1969) Studies with ubiquinone-depleted submitochondrial particles. Essentiality of ubiquinone for the interaction of succinate dehydrogenase, NADH dehydrogenase, and cytochrome b. Eur. J. Biochem. 9,299-310.
  • 4. Crane, F.L. & Morre, D.J. (1977) Evidence for coenzyme Q function in Golgi membranes; in Biomedical and Clinical Aspects of Coenzyme Q (Folkers, K. & Yamamura, Y., eds.) pp. 3-14, Elsevier, Amsterdam.
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  • 6. Sun, I.L., Sun, E.E., Crane, F.L & Morre, D.J. (1990) Evidence for coenzyme Q function in transplasma membrane electron transport. Biochem. Biophys. Res. Commun. 172,979-984.
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  • 8. Frei, B., Kim, M.C. & Ames, B. (1990) Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations. Proc. Natl. Acad. Sci. U.S.A. 87,4879-4883.
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  • 11. Ernster, L. & Beyer, R.E. (1991) Antioxidant functions of coenzyme Q; Some biochemical and pathophysiological implications; in Biomedical and Clinical Aspects of Coenzyme Q. (Folkers, K., Littaru, G.P. & Yamagami, Y., eds.) vol. 6, pp. 45-58, Elsevier, Amsterdam.
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  • 13. Forsmark, P., Aberg, F., Norling, B.,- Nordenbrand, K., Dallner, G. & Ernster, L (1991) Inhibition of lipid peroxidation by ubiquinol in submitochondrial particles in the absence of vitamin E. FEBS Lett. 285,39-43.
  • 14. Aberg, F., Appelkvist, E.L., Dallner, G. & Ernster, L. (1992) Distribution and redox state of ubiquinones in rat and human tissues. Arch. Biochem. Biophys. 295,230-234.
  • 15. Lang, J.K. & Packer, L. (1987) Quantitative determination of vitamin E and oxidized and reduced coenzyme Q by high-performance liquid chromatography with in-line ultraviolet and electrochemical detection. J. Chromatogr. 385,109-117.
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  • 18. Steinberg, D., Parthasarathy, S., Carew, T.E., Khoo, J.C. & Witztum, J.L. (1989) Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenesity. N. Engl. J. Med. 320,915-924.
  • 19. Valtersson, C., van Duyn, G., Verkleij, A.J., Chojnacki, T., de Krujiff, B. & Dallner, G. (1985) The influence of dolichol, dolichol esters, and dolichyl phosphate on phospholipid polymorphism and fluidity in model membranes. J. Biol. Chem. 260, 2742-2751.
  • 20. Lenaz, G. & Espoti, M.D. (1985) Physical properties of ubiquinone in model systems and membranes; in Coenzyme Q: Biochemistry, Bioenergetics and Clinical Applications of Ubiquinone (Lenaz, G., ed.) pp. 83-106, John Wiley, New York.
  • 21. Casu, A., Cottalasso, D., Pronzato, M.A., Rolla, C., Marinari, U.M. & Narri, G. (1986) Investigation of the role of ubiquinone in rat liver subcellular compartments. Cell. Biochem. Funct. 4,37-42.
  • 22. Halliwell, B. & Gutheridge, J.M.C. (1989) Free Radicals in Biology and Medicine, pp. 86-187. Clarendon Press, Oxford.
  • 23. Thelin, A., Schedin, S. & Dallner, G. (1992) Half-life of ubiquinone-9 in rat tissues. FEBS Lett. 313,118-120.
  • 24. Katen, A., Appelkvist, E.L. & Dallner, G. (1989) Age-related changes in the lipid compositions of rat and human tissues. Lipids 24,579-584.
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  • 26. Olsson, J.M., Eriksson, L.C. & Dallner, G. (1991) Lipid composition of intracellular membranes isolated from rat liver nodules in Wistar rats. Cancer Res. 51,3774-3780.
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  • 30. Reddy, J.K. (1990) Carcinogenicity of peroxisome proliferators: evaluation and mechanisms. Biochem. Soc. Trans. 18, 92-94.
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Bibliografia

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