Clofibrate and di(2-ethylhexyl)phthalate increase ubiquinone contents without affecting cholesterol levels

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 fatty acid beta-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, are discussed.