Hypolipidemic drugs can change the composition of rat brain lipids

Abstract

Hypolipidemic drugs are potent serum cholesterol lowering agents used for prevention of coronary heart disease. In addition to their cholesterol lowering effect, these drugs exhibit both pleiotropic beneficial and various neurological side effects. Therefore, we analysed effect of the hypolipidemic drugs, fenofibrate and statins, on membrane lipid composition in the rat brain tissue. Male Wistar rats were given 0.1 mg of fenofibrate, lovastatin, pravastatin, fluvastatin or placebo (control) once daily for six weeks. In rats treated with lovastatin or pravastatin, decreased cholesterol and increased ceramide monohexoside contents in the brain tissue were observed in comparison with control. Treatment with fluvastatin or lovastatin resulted in increased sphingomyelin and decreased diphosphatidylglycerol contents. The most important changes in the fatty acid profile were observed in ceramide monohexosides; treatment with fluvastatin decreased the content of saturated and increased the content of polyunsaturated fatty acids. Fenofibrate treatment led to decreased content of saturated fatty acids in phosphatidylethanolamines. In conclusion, statin treatment resulted in the decreased content of cholesterol and diphosphatidylglycerol associated with the increased content of sphingolipids in the rat brain tissue. As cholesterol and sphingolipids are important components of brain membranes, the observed alterations in the composition brain lipids might be involved in genesis of neurological and mental symptoms following statin therapy. © 2004 Tohoku University Medical Press.