Short-term treatment with low-dose pravastatin attenuates oxidative susceptibility of low-density lipoprotein in hypercholesterolemic patients

The effects of treatment with low-dose 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pravastatin on the changes of chemical composition and in vitro oxidative susceptibility of low-density lipoprotein (LDL) were studied in 20 type Ila hyperlipidemic patients with a plasma total cholesterol level > 240 mg/dL at the end of a diet control period for 3 months using the American Heart Association recommended step I diet. Treatment with pravastatin in a dose of 5 mg twice daily for 4 weeks resulted in lowering plasma total and LDL cholesterol levels by 17.0% and 22.9%, respectively. There was no further decline in plasma lipid thereafter. Chemical composition analysis showed that LDL particles did not contain significantly less cholesterol and thiobarbituric acid reactive substances (TBARS) until the end of 8 weeks (130.6 +/- 17.8 vs. 106.6 +/- 37.1 mg/mg protein, P < 0.05 and 0.16 +/- 0.06 vs. 0.08 +/- 0.02 nmol/mg protein, P < 0.005, respectively). Vitamin E, phospholipid, and triglyceride contents remained at the same levels throughout the study. In terms of oxidative kinetics, lag time and time to maximal diene concentration were not prolonged during the treatment period for 12 weeks, while total diene concentration and reaction rate were not significantly reduced until 8 weeks of treatment. Plasma enzyme activity of glutathione reductase and peroxidase, as well as the whole blood level of reduced and oxidized glutathione, remained similar during the study. In conclusion, pravastatin, at the low dose of 5 mg twice daily, produced a significant decline in plasma lipid levels to a steady-state range by 4 weeks; however, 8-weeks treatment is necessary to reduce the cholesterol and TBARS content, as well as to attenuate the oxidative susceptibility of LDL. These effects are not related to the antioxidant glutathione.