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      Effect of coenzyme Q10 and Ardisia japonica Blume on plasma and liver lipids, platelet aggregation, and erythrocyte Na efflux channels in simvastatin-treated guinea pigs

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          Abstract

          Forty guinea pigs were divided into four groups and fed 0.04% cholesterol based control diet, plus 0.05% simvastatin, and statin plus 0.1% CoQ10 or 10% Ardisia Japonica Blume (AJB) leave powder for 4 weeks. Plasma total cholesterol levels decreased significantly in all groups fed the statin-containing diet compared with that in guinea pigs fed the control diet ( P < 0.01). Plasma and liver triglycerides decreased significantly in the statin plus CoQ10 group compared with those in the control (both P < 0.05). Maximum platelet aggregation was significantly higher in the statin plus CoQ10 group than that in the other groups ( P < 0.05). Na-K ATPase activity increased in the statin group and decreased in the statin plus CoQ10 group ( P < 0.01). Na-K co-transport and Na passive transport decreased significantly in the control group compared with those in the other groups (both P < 0.05). Intracellular Na was highest in the statin group and lowest in the statin plus CoQ10 group and was correlated with Na-K ATPase activity. Thiobarbituric acid reactive substance production in platelet-rich plasma and liver tended to decrease in the statin plus CoQ10 group compared with those in the other groups. Plasma glutamic-pyruvic transaminase and glutamic-oxaloacetic transaminase increased significantly in the statin group compared with those in the control ( P < 0.05). These result suggest that antioxidant rich AJB did not have positive effects on cardiovascular disease parameters. The statin plus CoQ10 seemed to decrease cholesterol more efficiently than that of statin alone.

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          Most cited references41

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          Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans.

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            Coenzyme Q10 and statins: biochemical and clinical implications.

            Statins are drugs of known and undisputed efficacy in the treatment of hypercholesterolemia, usually well tolerated by most patients. In some cases treatment with statins produces skeletal muscle complaints, and/or mild serum CK elevation; the incidence of rhabdomyolysis is very low. As a result of the common biosynthetic pathway Coenzyme Q (ubiquinone) and dolichol levels are also affected, to a certain degree, by the treatment with these HMG-CoA reductase inhibitors. Plasma levels of CoQ10 are lowered in the course of statin treatment. This could be related to the fact that statins lower plasma LDL levels, and CoQ10 is mainly transported by LDL, but a decrease is also found in platelets and in lymphocytes of statin treated patients, therefore it could truly depend on inhibition of CoQ10 synthesis. There are also some indications that statin treatment affects muscle ubiquinone levels, although it is not yet clear to which extent this depends on some effect on mitochondrial biogenesis. Some papers indicate that CoQ10 depletion during statin therapy might be associated with subclinical cardiomyopathy and this situation is reversed upon CoQ10 treatment. We can reasonably hypothesize that in some conditions where other CoQ10 depleting situations exist treatment with statins may seriously impair plasma and possible tissue levels of coenzyme Q10. While waiting for a large scale clinical trial where patients treated with statins are also monitored for their CoQ10 status, with a group also being given CoQ10, physicians should be aware of this drug-nutrient interaction and be vigilant to the possibility that statin drugs may, in some cases, impair skeletal muscle and myocardial bioenergetics.
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              The ability of statins to inhibit bone resorption is directly related to their inhibitory effect on HMG-CoA reductase activity.

              Statins, which are inhibitors of 3-hydroxy-3-glutaryl-coenzyme A (HMG-CoA) reductase, decrease the hepatic biosynthesis of cholesterol by blocking the mevalonate pathway. Nitrogen-containing bisphosphonate drugs also inhibit the mevalonate pathway, preventing the production of the isoprenoids, which consequently results in the inhibition of osteoclast formation and osteoclast function. Therefore, we hypothesized that statins could affect bone metabolism in vivo through effects on osteoclastic bone resorption. In vitro, cerivastatin inhibited the parathyroid hormone (PTH)-stimulated bone resorption. Using a panel of 40 statin analogs, which showed variable effects on HMG-CoA reductase activity, we found that the ability of compounds to inhibit bone resorption is directly related to HMG-CoA reductase activity. However, in the thyro-parathyrodectomy (TPTX) model for bone resorption in the rat in vivo, cerivastatin did not prevent experimentally induced increases in bone resorption. The lack of effect of cerivastatin in this model is not related to a limited penetration of the target tissue (bone marrow), because a significant effect on HMG-CoA reductase activity was demonstrated in the total rat bone marrow cell extracts of rats posttreatment in vivo. Furthermore, cerivastatin inhibited protein prenylation in osteoclasts isolated from the rabbit bone marrow of rabbits after treatment in vivo. In contrast to other studies, none of the statins tested showed anabolic effects in parietal bone explant cultures. Taken together, we conclude that statins inhibit bone resorption in vitro, which correlates directly with the potency of the compounds for inhibition of HMG-CoA reductase activity. However, cerivastatin does not affect bone resorption in the rat TPTX model in vivo.
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                Author and article information

                Journal
                Nutr Res Pract
                Nutr Res Pract
                NRP
                Nutrition Research and Practice
                The Korean Nutrition Society and the Korean Society of Community Nutrition
                1976-1457
                2005-6168
                October 2012
                31 October 2012
                : 6
                : 5
                : 414-420
                Affiliations
                Department of Foods and Nutrition, Jeju National University, 1 Ara-dong, Jeju-si, Jeju 690-756, Korea.
                Author notes
                Corresponding Author: Jung Sook Kang, Tel. 82-64-754-3555, Fax. 82-64-725-2539, jungkang@ 123456jejunu.ac.kr
                Article
                10.4162/nrp.2012.6.5.414
                3506872
                23198020
                2f36d782-2719-4765-bcec-4e5f2c82d46e
                ©2012 The Korean Nutrition Society and the Korean Society of Community Nutrition

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 April 2012
                : 16 August 2012
                : 30 August 2012
                Categories
                Original Research

                Nutrition & Dietetics
                simvastatin,cholesterol,ardisia japonica blume,guinea pig,coq10
                Nutrition & Dietetics
                simvastatin, cholesterol, ardisia japonica blume, guinea pig, coq10

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