Study on COQ10 Antioxidant

Coenzyme Q10 (English name: Coenzyme Q10 or CoQ10), is a fat-soluble quinone compound, the formula is C59H90O4, molecular weight is 862, the structural formula is shown in Figure 1. It is yellow or light yellow crystal, odorless, tasteless, soluble in chloroform, benzene, carbon tetrachloride, soluble in acetone, petroleum ether and ethyl ether, slightly soluble in ethanol, insoluble in water and methanol, easily decomposed into reddish substance when exposed to light, stable to temperature and humidity, melting point is 49℃[1]. It is stable to temperature and humidity, with a melting point of 49℃[1]. In plants and animals, Coenzyme Q10 binds to the inner membrane of mitochondria, and participates in proton translocation, electron transfer, and ATP synthesis in the respiratory chain, which is mainly achieved by the extraction and isolation method, the chemical synthesis method, and the biosynthesis method.

Coenzyme Q10 has been synthesized by the method of synthesis of coenzyme Q10 and other methods. At present, the study of the antioxidant effect of coenzyme Q10 has become a hot spot, and this paper will briefly introduce the antioxidant effect of coenzyme Q10 and its mechanism.

1 Regulation of the antioxidant effects of coenzyme Q10

Animal organisms have both enzymatic and non-enzymatic antioxidant systems. Enzymatic systems include superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), while non-enzymatic systems include vitamins, amino acids, and metalloproteins [2].

In animals, coenzyme Q10 exists in the inner mitochondrial membrane and is closely related to the cellular energy production process. It plays a role in the transfer of electrons and transport proteins in the process of cellular respiration and ATP production, and it exists in two forms: quinone (oxidized form, CoQ10) and phenol (reduced form, CoQ10H2), most of which are in the form of oxidized form, and CoQ10H2 is unstable and susceptible to oxidative stress. Relevant studies have shown that CoQ10H2 mainly plays an antioxidant role by inhibiting free radical-mediated oxidative damage to membrane lipoproteins, scavenging free radicals and inhibiting oxidative stress when free radicals attack the mitochondrial membrane. Peng Liang et al. (2011) showed that coenzyme Q10 can significantly increase the activities of superoxide dismutase and glutathione peroxidase, and has antioxidant effects on human body through human experiments. Currently, in medicine, Coenzyme Q10 has been used as an adjuvant in the treatment of various diseases, showing that Coenzyme Q10 can scavenge free radicals and inhibit oxidative stress by generating superoxide anion radicals, thus demonstrating antioxidant effects [3]. Coenzyme Q10 is also associated with atherosclerosis. Low-density lipoprotein (LDL) is a key factor in atherosclerosis, and CoQ10H2 can improve the resistance of LDL free radicals and improve atherosclerosis, and some studies have also shown that Coenzyme Q10 can synergistically regulate the antioxidant effects with antioxidants such as vitamin E and ascorbic acid.

2 Mechanism of the antioxidant effect of Coenzyme Q10

2.1 Removal of free radicals

2.1.1 Reduction of oxidative stress    

Free radicals refer to atoms, groups of atoms, molecules and ions with unpaired valence electrons, which are intermediate metabolites of many biochemical reactions in human tissues. Under normal circumstances, the generation and metabolism of free radicals in the body are in dynamic balance. If the body is subjected to harmful stimuli in vitro or in vivo, the number of free radicals in the body will increase, the antioxidant capacity will be reduced, and toxic effects will be produced at the level of molecules, cells, and organs, which will damage the cellular components, disrupt the cellular structure, and cause damages to the body, and the process is known as oxidative stress.

Coenzyme Q10 is an oxidoreductase mainly concentrated in mitochondria. It is a natural antioxidant and free radical scavenger, acting as a convergence point of oxidative respiratory chains of different actors in mitochondria, participating in oxidative phosphorylation, and generating ATP to provide energy for mitochondria [4]. Insufficient levels of coenzyme Q10 in mitochondria will reduce the activity of certain antioxidant enzymes in mitochondria and decrease the scavenging ability of free radicals. Peng Liang et al. (2012) investigated the antioxidant effects of Coenzyme Q10 in naturally aging rats, and showed that exogenous Coenzyme Q10 intake could have an in vivo antioxidant and ageing-prolonging effect, and that Coenzyme Q10 could effectively reduce the levels of lipid peroxylates (MDA) and lipids (Lip), and increase the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the animals. 

Dongwook Lee et al. (2014) investigated the protective effect of coenzyme Q10 in scavenging reactive oxygen radicals against oxidative stress in neuronal cells in neurodegenerative diseases, and showed that coenzyme Q10 could protect neuronal cells subjected to oxidative stress by modulating the Bax/Bad-mediated mitochondrial apoptotic pathway and preventing mitochondrial alterations to protect retinal ischemia and protein expression. Coenzyme Q10 can protect retinal nerve cells from oxidative stress by modulating the Bax/Bad-mediated apoptotic pathway and preventing mitochondrial alterations to protect against retinal ischemia and protein expression, thereby alleviating ischemic damage to the retina.

2.1.2 Stabilization of cell membrane structure 

As an important component of cells, biological membranes are able to participate in physiological activities such as material transport, information transfer, energy exchange and cell recognition. Free radicals mainly attack the polyunsaturated fatty acids in the phospholipids of biological membranes, causing membrane lipid peroxidation reaction, causing damage to the plasma membrane of biological membranes, mitochondrial membranes, Golgi membranes and endoplasmic reticulum membranes, etc., decreasing or eliminating the activity of many enzymes on the membranes, leading to an increase in the permeability of the membranes, which will change the state of the liquid mosaic of the biological membrane system and cause diseases, so that the removal of free radicals can stabilize the conformation and structure of cellular membranes. Therefore, scavenging free radicals can stabilize the configuration and structure of cell membranes. As an auto-oxidant, Coenzyme Q10 can act as a stimulant, produce ATP, scavenge free radicals, influence enzyme activities, maintain the integrity of calcium ion channels, and thus directly protect and restore the structure of biological membranes.

2.1.3 Inhibition of apoptosis    

Coenzyme Q10 can increase the efficiency of ATP production, inhibit the opening of mitochondrial permeability transition channels and depolarization of mitochondria, and directly remove free radicals and protect mitochondrial DNA, thus preventing mitochondrial damage and free radicals, and thus inhibiting cellular apoptosis [5]. It has been suggested that the mechanism of cellular apoptosis inhibition by coenzyme Q10 may be through the blockage of the mitochondrial membrane transit pore. Macromolecules with a relative molecular mass of more than 1500 enter the mitochondria by opening the mitochondrial transit pore, leading to mitochondrial collapse, and by preventing the opening of this pore, coenzyme Q10 prevents the triggering of cellular apoptosis[6]. Rosario et al. (2002) demonstrated that coenzyme Q10 significantly decreased the amount of mitochondrial DNA that was induced by an excimer laser. Rosario et al. (2002) demonstrated that coenzyme Q10 significantly reduced the rate of excimer laser-induced apoptosis in rabbit corneal cells, and Menke et al. (2003) reported that coenzyme Q10 could reduce the toxicity of rotenone on neuronal nutrients by preserving the mitochondrial membrane potential. They suggested that coenzyme Q10 could regulate and produce cellular protective effects by increasing the cellular resistance to apoptotic steps, i.e., by lowering the mitochondrial membrane potential. It was further demonstrated that Coenzyme Q10 had apoptosis-reducing effects on other cells, such as dopamine neuron cells[7] and corneal fibroblasts[8].

2.2 Coenzyme Q10 and atherosclerosis    

Arterial atherosclerosis (AS) is a chronic inflammatory disease occurring in the vascular wall due to the accumulation of fat [9], and epidemiologic studies have demonstrated that plasma LDL levels are one of the important risk factors for the development of cardiovascular disease [10]. Oxidized low-density lipoprotein (ox-LDL) is a chemokine present in monocytes that can differentiate into macrophages, leading to the formation of lipid-filled foam cells and the development of fatty streaks, and is an early stage in the formation of atherosclerotic plaques. At the same time, the cytotoxic effect of LDL on vascular endothelial cells increases platelet activation and stimulates smooth muscle cell migration and proliferation, thus initiating the process of atherosclerosis [11].

Coenzyme Q10 can reduce or delay the oxygenation of LDL, and its mechanism of action can be summarized as follows: Coenzyme Q10 has a site-specific antioxidant effect that protects the lipid and protein components of LDL from oxidative damage, whereas CoQ10H2 has a strong antioxidant ability that can efficiently terminate free radical chain reactions and inhibit the effects of various oxygenation inducers, and inhibit LDL lipid peroxidation under different oxidative stress conditions (strong or mild), thereby inhibiting the formation and progression of atherosclerosis [12]. Under different oxidative stress conditions (strong or mild), CoQ10H2 inhibits LDL lipid peroxidation, thereby inhibiting the formation and development of atherosclerosis [12]. Immunologically, ox-LDL is the autoantigen of atherosclerosis patients, which can stimulate the body to produce corresponding antibodies, resulting in antigen-antibody reactions that are involved in the formation of atherosclerosis. Sun Ji et al. (2015) reported that coenzyme Q10 could increase the amount and improve the function of serum high-density lipoprotein (HDL) in rats with atherosclerosis, reduce the level of oxidative stress and affect the expression of aortic inflammatory factors, which may play a role in inhibiting the formation of AS and reducing the rupture of plaques.

2.3 Synergistic antioxidant effects of coenzyme Q10 with other substances    

In the animal body, free radical scavenging antioxidants do not exist alone, but often work in synergy with other antioxidants. Currently, coenzyme Q10 is commonly used with vitamin E, ascorbic acid and L-carnitine to exert synergistic antioxidant effects.

2.3.1 Coenzyme Q10 and Vitamin E

Coenzyme Q10 is a fat-soluble substance found in cell membranes and organelle membranes, and vitamin E, as a fat-soluble vitamin, can synergize its antioxidant effects in the body, and is an important antioxidant that blocks free radical chain reaction [13]. Vitamin E can block the free radical chain reaction, CoQ10H2 can inhibit the initiation and termination of lipid peroxidation, and CoQ10H2 can restore the α-tocopherol acyl radical produced by vitamin E during free radical scavenging, regenerate and conserve vitamin E to play an antioxidant role. In case of oxidative stress, vitamin E can be converted to a stabilized state with the synergistic effect of Coenzyme Q10, which accelerates the rate of lipid peroxidation. Bai Ningning et al. (2007) studied the antioxidant effects of soluble Coenzyme Q10 and vitamin E on aged mice and D-galactose model mice, and showed that soluble Coenzyme Q10 and vitamin E have synergistic antioxidant effects, which can prevent and delay aging.

2.3.2 Coenzyme Q10 and Ascorbic Acid   

Ascorbic acid, also known as vitamin C, is one of the best-known members of the class of known antioxidant compounds. It contains a gamma-ascorbyl-lactone ring [14], which increases its reductive and antioxidant properties upon the donation of one or two electrons to the hydroxyl radical, which is responsible for its antioxidant properties. It can remove free radicals, reduce α-tocopherol acyl radicals and prevent the initiation of α-tocopherol hydroxyl radical-mediated chain reaction. Therefore, it is believed that vitamin E and ascorbic acid can synergize to inhibit lipid peroxidation, and then it is speculated that coenzyme Q10 has a synergistic effect with ascorbic acid.

2.3.3 Coenzyme Q10 and L-carnitine   

 L-carnitine, also known as levocarnitine and vitamin BT, is related to fatty acid metabolism in animals. Its main function is to act as a carrier to transport long-chain fatty acids from the outside of the mitochondrial membrane to the inside of the membrane in order to promote the β-oxygenation of fatty acids, and to promote the conversion of fatty acid metabolism into energy [15], and it is a very important antioxidant in the body of animals. As an antioxidant, coenzyme Q10 can work together with L-carnitine to strengthen the antioxidant pool and enhance the antioxidant power of cells. Geng Ai-lian et al. (2005) demonstrated that the simultaneous addition of L-carnitine and Coenzyme Q10 to the diet could improve the metabolism of liver lipids and reduce the antioxidant effect in broiler chickens with ascites.

3 Other physiological functions of Coenzyme Q10

3.1 Enhancement of immune function 

Coenzyme Q10 is a non-specific immunostimulant present in the body, which can enhance the vitality of immune cells to kill pathogens, increase the number of leukocytes, immunoglobulin and specific antibodies, and thus improve the immune function of the body. In animal organisms, Coenzyme Q10 can increase the proliferation of splenic lymphocytes induced by ConA, enhance the delayed-type mutation response, activate the phagocytosis efficiency of monocyte-macrophage phagocytosis system, and increase the activity of natural killer cells (NK) cells. We believe that the modulating effect of Coenzyme Q10 on the immune function of mice may be mainly through the activation of the activity of NK cells, which can then exert the function of T cells and make the macrophage function. We believe that the modulating effect of Coenzyme Q10 on immune function in mice may be mainly achieved by activating NK cells, which in turn exerts the function of T cells and activates macrophages to become antigen-presenting cells, which participate in the immune response processes of recognizing, phagocytosing, and processing antigens, as well as delivering immune messages.

In an immunomodulation experiment of Coenzyme Q10 in mice, Xu Caiju et al. (2007) demonstrated that Coenzyme Q10 enhanced specific and non-specific immunity in mice, and the mechanism of its action may be related to the activation of NK cells, T cells, macrophage cells, scavenging of oxygen radicals, stabilization of membrane potential, and so on.

3.2 Other functions of coenzyme Q10 

Patients with cardiac disease, hypertension and other cardiovascular diseases have been found to have low levels of coenzyme Q10 in their tissues and plasma. Therefore, supplementation of exogenous coenzyme Q10 can make up for the deficiencies in plasma coenzyme Q10, improve the respiratory efficiency of the mitochondria and the production of ATP, and can be used as a cardiac metabolism rejuvenating agent; coenzyme Q10 is able to eliminate adverse reactions such as rhabdomyolysis caused by statin drugs, and assist statin drugs in exerting their blood lipid-lowering effects. Coenzyme Q10 can effectively eliminate the adverse effects of statins, such as rhabdomyolysis, and assist statins in lowering blood lipids; clinical experiments have shown that patients born with a deficiency of coenzyme Q10 are susceptible to cerebral myopathy, and a small amount of coenzyme Q10 supplementation can effectively improve the therapeutic efficacy of coenzyme Q10 [16]; coenzyme Q10 is also involved in life activities such as cellular messaging and gene expression, and has the function of improving the obstacles in microcirculation and facilitating learning and memory [17]. Coenzyme Q10 is also involved in life activities such as cellular information transfer and gene expression.

4 Studies on the application of Coenzyme Q10 in livestock and poultry production

In recent years, studies on the antioxidant effects of coenzyme Q10 have mainly focused on animal disease models. Geng Ailian et al. (2005) used low temperature treatment to induce ascites in broiler chickens, and studied the effects of adding L-carnitine and coenzyme Q10 to the diet alone and simultaneously on the performance of broiler chickens and the susceptibility to ascites, which showed that the addition of coenzyme Q10 did not have a significant effect on the performance of broiler chickens, but it could reduce the mortality rate of broiler chickens suffering from ascites; Yang J. et al. (2011) showed that coenzyme Q10 alone could decrease the mortality rate of ascites caused by high-energy feed. Yang Jing et al. (2011) in the high-energy feed-induced broiler ascites and sudden death experiment showed that the addition of coenzyme Q10 alone can reduce high-energy-induced broiler deaths, sudden death, ascites and pericardial effusion, so that the number of deaths of broiler chickens from 25/100 to 2/100, the number of sudden deaths from 25/100 to 1/100; Gu Ying (2011) in the avian gout Clinical Pathology of Avian Gout study mentioned that the addition of coenzyme Q10 to diets can significantly reduce blood pressure, but also reduced mortality of broiler chickens. In the clinical pathology study of avian gout, Gu Ying (2011) mentioned that the addition of coenzyme Q10 to the diet significantly reduced the levels of uric acid (UA), muscle anesthesia (Cr), and urea nitrogen (BUN), and the degree of renal tubular and glomerular pathology in chickens in the two groups was significantly less than that in the group of chickens in which CoQ10 was not added to the diet, as indicated by the reduction of renal tubular epithelial cell edema, the reduction of inflammatory cells, and the clearing of the renal tubular and glomerular structures.

In the study of the effects of hypercholesterolemia on myocardial energy metabolism in rabbits and the interventional effects of atorvastatin and coenzyme Q10, Runbo Qu (2012) showed that ATP and coenzyme Q10 levels in myocardial mitochondria of rabbits were significantly increased in the atorvastatin-coenzyme Q10 group compared with the atorvastatin group, suggesting that exogenous supplementation of coenzyme Q10 can increase the amount of coenzyme Q10 in the myocardial mitochondria and alleviate the obstacle of myocardial mitochondrial energy metabolism. Gao Xiuge et al. (2015) investigated the effect of coenzyme Q10 on pork quality and showed that the addition of coenzyme Q10 to diets significantly improved meat quality and slowed down the rate of discoloration, stabilizing the color of the meat, and the appropriate amount of coenzyme Q10 was determined to be 10 mg kg-1 by combining the production cost and other indexes; Yu Q. et al. (2015) used cyclic tetraphosphamide (CTX) to induce a rapid induction of osteoporosis in a rat model. (2015) used cyclophosphamide (CTX) to rapidly induce an osteoporosis model in rats, and observed the effects of Coenzyme Q10 on the microstructure and biomechanical properties of cancellous bone in the femur of CTX rats, and compared the results with those of alendronate sodium (ALD), which showed that the microstructural parameters of bone volume fraction and trabecular thickness of femur in the rats in the Coenzyme Q10 group were significantly repaired, and the biomechanical parameters of bone, except for rupture strain, were significantly repaired, indicating that Coenzyme Q10 has a certain ability to repair the microstructural and biomechanical properties of femur in CTX rats. This indicates that Coenzyme Q10 has the ability to repair the microstructure of the femur in CTX rats, and its ability to repair bone quality and reduce the risk of femur fracture is better than that of ALD, and it has a good effect on anti-osteoporosis.

5 Summary

To sum up, Coenzyme Q10 is an indispensable prerequisite for the normal physiological functions of various types of cells, and it mainly exerts antioxidant effects by removing free radicals, atherosclerosis, and synergizing with other antioxidant substances. At the same time, it also enhances immune activity and plays an important role in the improvement of the heart, liver and other solid organs of the animal body, as well as in the treatment of eye diseases. Therefore, the study of the regulation of the antioxidant effect of Coenzyme Q10 and its mechanism is of great significance to the improvement of animal performance and the protection of animal health.

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