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Replies to post #6658 on Synaptogenix Inc (SNPX)
08/18/18 11:20 AM
Statin-induced changes in mitochondrial respiration in blood platelets in rats and human with dyslipidemia.
Vevera J1, Fišar Z, Nekovárová T, Vrablík M, Zlatohlávek L, Hroudová J, Singh N, Raboch J, Valeš K.
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Abstract
3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used drugs for lowering blood lipid levels and preventing cardiovascular diseases. However, statins can have serious adverse effects, which may be related to development of mitochondrial dysfunctions. The aim of study was to demonstrate the in vivo effect of high and therapeutic doses of statins on mitochondrial respiration in blood platelets. Model approach was used in the study. Simvastatin was administered to rats at a high dose for 4 weeks. Humans were treated with therapeutic doses of rosuvastatin or atorvastatin for 6 weeks. Platelet mitochondrial respiration was measured using high-resolution respirometry. In rats, a significantly lower physiological respiratory rate was found in intact platelets of simvastatin-treated rats compared to controls. In humans, no significant changes in mitochondrial respiration were detected in intact platelets; however, decreased complex I-linked respiration was observed after statin treatment in permeabilized platelets. We propose that the small in vivo effect of statins on platelet energy metabolism can be attributed to drug effects on complex I of the electron transport system. Both intact and permeabilized platelets can be used as a readily available biological model to study changes in cellular energy metabolism in patients treated with statins.
Statins protect against cardiovascular-related mortality but induce skeletal muscle toxicity. To investigate mechanisms of statins, we tested the hypothesis that statins optimized cardiac mitochondrial function but impaired vulnerable skeletal muscle by inducing different level of reactive oxygen species (ROS).
The role of statins in both cognitive impairment and protection against dementia: a tale of two mechanisms
Bob G. Schultz, Denise K. Patten, and Daniel J. Berlaucorresponding author
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Abstract
Nearly 30% of adults 40 years and older in the United States are on a statin. Their widespread use heightens the importance of careful consideration of their varied effects on the body. Although randomized controlled trials have not confirmed cognitive impairing effects with statins, continuing evidence suggests statins have the ability to cause reversible cognitive impairment in some patients. Paradoxically, statins have also been shown to decrease the risk of dementia, Alzheimer’s disease, and improve cognitive impairment in some cases. However, randomized controlled trials have similarly failed to find the beneficial effect. Supporting evidence for both claims is compelling whereas known limitations of the clinical trials may explain the lack of findings. This narrative review aims to explain why there is still controversy and how both effects can, and may, be possible. The mechanisms that have been hypothesized for each effect are seemingly independent from one another and may explain the contradicting results. Being mindful of the complex effects of statins, health care providers need to be able to identify patients who are at risk for or already experiencing cognitive impairment from statin use while also identifying those who could potentially decrease their risk of dementia with statins.
