Uptake, induction and distribution of ubiquinone and a-tocopherol

Ubiquinone (UQ) and a-tocopherol are the major lipid-soluble antioxidants in animal tissues. Appropriate amounts of these lipids have to be present in tissues and subcellular membranes. Uptake from the diet was investigated and it was also analyzed to which extent the tissue amount may be increased by induction of biosynthesis. Dietary administration of UQ to rats resulted in limited uptake, 2-3% of the total dose to the blood and liver, where it was found partly in reduced form. No uptake was observed in the heart and kidney. The uptake of UQ did not influence the endogenous biosynthesis of this lipid. In contrast to UQ uptake, dietary administration of a-tocopherol over 6 weeks inereased continuously the level of this lipid in kidney, heart, muscle and brain. a-Tocopherol was present in the highest concentration in Golgi vesicles in the liver and after uptake it was generally distributed in all organelles. On the contrary, dietary UQ exhibited a selective uptake at the cellular level. Dietary administration of clofibrate and di(2-ethyhexyl)phthalate increased UQ levels in the liver, muscle, heart and blood but not in the brain. Probucol, which is an antioxidant given in the diet, decreased somewhat UQ levels. Administration of the peroxisomal inducers, acetylsalicylic acid, 2-ethylhexanoic acid, thyroxine and dehydroepiandrosterone, increased the content of UQ in the liver, and to some extent in the kidney and muscle. The increase of the UQ level in the liver was in direct proportion to the increase in peroxisomal B-oxidation. A linear relationship between the increase in liver UQ and the decrease in blood cholesterol levels was found. Cholesterol content reached the final concentration in the rat brain after 2 months while dolichol increased 100-fold during the first 10 months and was further elevated up to 24 months of age. UQ content was increased in the first few months only and remained constant thereafter. In all regions and subcellular fractions investigated, 70% UQ-9 and 30% UQ-10 was found and a-tocopherol level in all brain regions was constant after 3 weeks of birth. Blood lipids were extracted with petroleum ether/methanol/water and analyzed after reduction on reversed phase HPLC by using a binary gradient with solvents containing lithium perchlorate. For quantitation of UQ and tocopherols, an electrochemical detector was employed. The procedure described is especially efficient for study of blood in hyperlipidemia.