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.statin; fibrate; brain; lipids; fatty acid

Fluvastatin Alters Psychomotor Performance and Daily Activity but not the Spatial Memory in Rats

“…Effects of fluvastatin in the rat brain were shown by Vecka et al (2004). Another study reported that lovastatin and simvastatin strongly reduced the levels of free cholesterol in synaptozomal plazma membranes and lovastatin and pravastatin significantly reduced cholesterol levels in the exofacial membrane leaflet.…”

“…The effects of several statins on lipid composition of the brain in rats, including fluvastatin, were observed by Vecka et al (2004), in which fluvastatin, an important member of the statin family, was shown to increase sphingomyelin and to decrease diphosphatidylglycerol contents in rat brains. Yet, the most important changes in the fatty acid profile being in the ceramide monohexosides, lead to a decrease in the content of saturated fatty acids and an increase in the content of polyunsaturated fatty acids.…”

PCSK9 Inhibitors and Neurocognitive Adverse Events: Exploring the FDA Directive and a Proposal for N-of-1 Trials

“…Cholesterol is a principal component of myelin, a fatty sheath that serves an essential role in cellular signaling and blood-brain barrier integrity [7]. Statins, regardless of their lipophilicity and ability to penetrate the blood-brain barrier, alter the composition of brain lipids in rat models [8]. Additionally, reduced serum cholesterol may also enhance blood-barrier permeability, exposing the CNS to normally barred toxins [9].…”

Simvastatin Impairs Spatial Memory in Rats at a Specific Dose Level

“…Glial cells use HMG-CoAR as the rate limiting enzyme in the synthesis of cholesterol (Snipes and Suter 1997). Vecka et al (2004) reported that fenofibrate, fluvastatin, lovastatin and pravastatin alter the brain lipid composition in rats. Simvastatin has also been shown to reduce brain cholesterol synthesis in guinea pigs (Lutjohann et al 2004).…”