ubiquinone and gamma-sitosterol

Statin pharmaceuticals, heavily prescribed in the treatment of hypercholesterolemia, are competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGR). In plants, these compounds also inhibit HMGR, which regulates cytosolic isoprenoid biosynthesis in the mevalonic acid (MVA) pathway. Phytotoxicity was evaluated in the higher aquatic plant Lemna gibba exposed to atorvastatin and lovastatin for 7-days by measuring the concentrations of sterols and ubiquinone; products downstream in the MVA pathway. The efficiency of the parallel and unaffected methylerythritol phosphate pathway (MEP) was also evaluated by measuring the end product, plastoquinone. Statin treatment caused an accumulation of plastoquinone, and unexpectedly, ubiquinone, an artifact likely due to metabolite sharing from the plastidial MEP pathway. Statins were, however, highly phytotoxic to L. gibba and HPLC-UV analysis of plant extracts showed significantly decreased concentrations of both stigmasterol and beta-sitosterol, which are critical components of plant membranes and regulate morphogenesis and development. EC10 values for atorvastatin and lovastatin were as small as 26.1 and 32.8 microg/L, respectively. However, hazard quotients indicated that statins present little risk to the model higher aquatic plant Lemna gibba at environmentally relevant concentrations, even though pathway-specific endpoints were 2-3 times more sensitive than traditional gross morphological endpoints typically used in risk assessment.

Topics: Atorvastatin; Chromatography, High Pressure Liquid; Heptanoic Acids; Herbicides; Hydroxymethylglutaryl CoA Reductases; Lovastatin; Mevalonic Acid; Models, Chemical; Pharmaceutical Preparations; Plants; Plastoquinone; Pyrroles; Risk Assessment; Sitosterols; Sterols; Ubiquinone; Ultraviolet Rays

In experiments with male Wistar rats the influence of the non-saponifiable constituents of dietary fats: dl-alpha-tocopherol (60 ppm), dl-gamma-tocopherol (480 ppm), ubiquinone (96 ppm) and beta-sitosterol (3035 ppm) on the tocopherol status was investigated, considering the fatty acid composition of the tested fats. For a test period of eight weeks the animals were fed isoenergetic diets containing three types of dietary fats: corn oil (60% PUFA), a kind of "stripped corn oil" (60% PUFA) and butter (nearly 5% PUFA). Independent of the PUFA-content of the diet, the tocopherol supplementations were able to stabilize the erythrocyte membrane; the calculated hemolysis rates were about 2%. The absence of tocopherols in the diets ("stripped corn oil", butter) caused an increase of the hemolysis rate up to 70% after two weeks. The original amounts of tocopherols in corn oil tended to minimize the hemolysis. Ubiquinone and beta-sitosterol did not reduce the hemolysis rates when they were applied without tocopherols. With respect to creatine-phosphokinase activity, creatine and creatinine excretion the results were similar. Plasma and erythrocyte levels of alpha- and gamma-tocopherol were determined in all groups and discussed in connection with the other examined parameters of tocopherol status. The ultimate result of this experiment is that the content of tocopherols in dietary fats is not always adequate to keep vitamin E status normal, especially if polyunsaturated fatty acid content is high in the diet. Reflecting the vitamin E adequacy of dietary fats, not only alpha-tocopherol but also gamma-tocopherol should be much more considered than previously.

Topics: Animals; Butter; Dietary Fats; Dose-Response Relationship, Drug; Fatty Acids, Unsaturated; Hemolysis; Male; Rats; Rats, Inbred Strains; Sitosterols; Structure-Activity Relationship; Triglycerides; Ubiquinone; Vitamin E; Zea mays