Ubiquinone Ameliorates Simvastatin Induced Respiratory Chain Complex Function Impairment in High‐Fat High‐Cholesterol Diet Fed Mice

Abstract

Long‐term statins therapy is the primary treatment of hyperlipidemia. A ubiquinone (Co‐enzyme Q10, CoQ10) supplement ameliorates the statins side effects, including skeletal muscle and liver damage, whereas the mechanism involving respiratory chain complex function in a hyperlipidemia animal model remains unknown. Herein, it is reported that the administration of CoQ10 increases plasma CoQ10 level significantly without affecting the lipid lowering effects of statins in high‐fat high cholesterol diet fed mice. Compared with thr statins group, the combination therapy of CoQ10 and statin (Simva + CoQ10) reduces the activity enhancement of plasma CK, ALT, and AST, and restores the activity of complex I in skeletal muscle (2.7‐fold increased) and liver (42% increased). Moreover, the activities of complex II are increased in the muscle (29% increased) and liver (5.8‐folds increased) significantly. Statins decrease the total CoQ10 concentration in mitochondria, while Simva + CoQ10 restore the total CoQ10 concentration in mitochondria from muscle (41% increased) and liver (1.1‐folds increased), respectively. Therefore, administration of CoQ10 ameliorates the function loss of mitochondria respiratory chain complex induced by statins in muscle and liver are concluded. Practical Applications: Statins are widely used in clinical treatment of hypercholesterolemia and atherosclerotic diseases via inhibiting the synthesis of mevalonic acid to achieve the purpose of reducing endogenous cholesterol loading, to display anti‐inflammatory effects, and to stabilize the atherosclerotic plaques. However, the shortage of MVA may cause the low level of ubiquinone which subsequently leads to increasing various side effects, including muscle and liver damage. This study introduces a novel combined administration which could ameliorate the statins induced muscle and liver damage for hypercholesterolemia individuals. Moreover, the method shows a beneficial effect on mitochondrion integrity and functions in skeletal muscle and liver. Statin administration inhibits the 3‐hydroxy‐3‐methyl glutaryl coenzyme A reductase (HMGCoA‐R), which subsequently decreases the level of endogenous Co enzyme Q10 (CoQ). CoQ supplementation increases the level of CoQ in mitochondria, and ameliorates the function loss of mitochondrial respiratory chain complex induced by statins.