Ubiquinone antioxidant

Hence we study the level of LDL lipoperoxides in patients with atherosclerosis who had been for a long-time treated with HMG-CoA-reductase inhibitors in monotherapy as well as in combination with natural or synthetic antioxidants such as ubiquinon Qio and probucol in double-blind placebo cmitrolled trials [36,37]. The treatment of patients with inhibitor of cholesterol and ubiquinon Qio biosynthesis pravastatine alone in daily dose 40 mg during 6 months was followed by accumulation of LDL lipohydropooxides in the blood plasma [36] (Figure 17). On the other hand the 6 months administration of the same dose of pravastatine in combination with natural antioxidant ubiquinon Qw in daily dose 60 mg sharply decreased even initial LDL lipoperoxides level in the plasma of patients [36] (Figure 17). 

Figure 17. The LDL lipoperoxide levels in the blood of patients with atherosclerosis after 6 months treatment with HMG-CoA-reductase inhibitor - pravastatin (40 mg daily) or pravastatin in combination with natural antioxidant ubiquinon Qio (60 mg daily).

Ubiquinone, known also as coenzyme Q, plays a crucial role as a respiratory chain electron carrier transport in inner mitochondrial membranes. It exerts this function through its reversible reduction to semiquinone or to fully hydrogenated ubiquinol, accepting two protons and two electrons. Because it is a small lipophilic molecule, it is freely diffusable within the inner mitochondrial membrane. Ubiquinones also act as important lipophilic endogenous antioxidants and have other functions of great importance for cellular metabolism. ... 

A large number of nonenzymatic compounds, including tocopherols, caroti-noids, vitamins C and D, steroids, ubiquinones, thiols, uric acid, bilirubin, ino-sine, taurine, pyruvate, CRP, and so on, demonstrate qualitative antioxidant properties under experimental conditions. However, the quantitative relevance of most findings remains unclear. 

In the last decade numerous studies were dedicated to the study of biological role of nonenzymatic free radical oxidation of unsaturated fatty acids into isoprostanes. This task is exclusively difficult due to a huge number of these compounds (maybe many hundreds). Therefore, unfortunately, the study of several isoprostanes is not enough to make final conclusions even about their major functions. F2-isoprostanes were formed in plasma and LDL after the treatment with peroxyl radicals [98], It is interesting that their formation was observed only after endogenous ascorbate and ubiquinone-10 were exhausted, despite the presence of other antioxidants such as urate or a-tocopherol. LDL oxidation was followed by... 

The effects of antioxidants on protein oxidation were also studied in animal experiments. Barja et al. [73] demonstrated that feeding guinea pigs with vitamin C decreased endogenous protein oxidative damage in the liver. Administration of the mixture of antioxidants containing Trolox C, ascorbic palmitate, acetylcysteine, (3-carotene, ubiquinones 9 and 10, and (+)-catechin in addition to vitamin E and selenium to rats inhibited heme protein oxidation of kidney homogenates more efficiently than vitamin E + selenium [74]. 

Ubiquinones (coenzymes Q) Q9 and Qi0 are essential cofactors (electron carriers) in the mitochondrial electron transport chain. They play a key role shuttling electrons from NADH and succinate dehydrogenases to the cytochrome b-c1 complex in the inner mitochondrial membrane. Ubiquinones are lipid-soluble compounds containing a redox active quinoid ring and a tail of 50 (Qio) or 45 (Q9) carbon atoms (Figure 29.10). The predominant ubiquinone in humans is Qio while in rodents it is Q9. Ubiquinones are especially abundant in the mitochondrial respiratory chain where their concentration is about 100 times higher than that of other electron carriers. Ubihydroquinone Q10 is also found in LDL where it supposedly exhibits the antioxidant activity (see Chapter 23). 

Contemporary interest in ubiquinones is explained by their potential antioxidant activity and the possibility of using these nontoxic natural compounds as pharmaceutical agents. But it should be noted that ubiquinones are not vitamins and that they are synthesized in humans. Taking into account a high level of ubiquinones in mitochondria, the effective supplementation of ubiquinones to fight against free radical-mediated damage seems to be a hard task. 

There are two kinds of redox interactions, in which ubiquinones can manifest their antioxidant activity the reactions with quinone and hydroquinone forms. It is assumed that the ubiquinone-ubisemiquinone pair (Figure 29.10) is an electron carrier in mitochondrial respiratory chain. There are numerous studies [235] suggesting that superoxide is formed during the one-electron oxidation of ubisemiquinones (Reaction (25)). As this reaction is a reversible one, its direction depends on one-electron reduction potentials of semiquinone and dioxygen. 

As already mentioned, another mechanism of antioxidant activity of ubiquinones is scavenging of free radicals by ubihydroquinones (Reaction (26)) ... 

This mechanism is now considered to be of importance for the protection of LDL against oxidation stress, Chapter 25.) The antioxidant effect of ubiquinones on lipid peroxidation was first shown in 1980 [237]. In 1987 Solaini et al. [238] showed that the depletion of beef heart mitochondria from ubiquinone enhanced the iron adriamycin-initiated lipid peroxidation whereas the reincorporation of ubiquinone in mitochondria depressed lipid peroxidation. It was concluded that ubiquinone is able to protect mitochondria against the prooxidant effect of adriamycin. Inhibition of in vitro and in vivo liposomal, microsomal, and mitochondrial lipid peroxidation has also been shown in studies by Beyer [239] and Frei et al. [240]. Later on, it was suggested that ubihydroquinones inhibit lipid peroxidation only in cooperation with vitamin E [241]. However, simultaneous presence of ubihydroquinone and vitamin E apparently is not always necessary [242], although the synergistic interaction of these antioxidants may take place (see below). It has been shown that the enzymatic reduction of ubiquinones to ubihydroquinones is catalyzed by NADH-dependent plasma membrane reductase and NADPH-dependent cytosolic ubiquinone reductase [243,244]. 

The administration of Qio or quercetin to rats protected against endotoxin-induced shock in rat brain [252]. It was found that the pretreatment with these antioxidants diminished the shock-induced increase in brain MDA and nitric oxide levels. Interesting data have been obtained by Yamamura et al. [253] who showed that ubiquinone Qi0 is able to play a double role in mitochondria. It was found that on the one hand, Q10 enhanced the release of hydrogen peroxide from antimycin A- or calcium-treated mitochondria, but on the other hand, it inhibited mitochondrial lipid peroxidation. It was proposed that Q10 acts as a prooxidant participating in redox signaling and as an antioxidant suppressing permeability transition and cytochrome c release. 

Coenzyme Q10, also known as CoQ, CoQlO, and ubiquinone, is found in the mitochondria of many organs, including the heart, kidney, liver, and skeletal muscle. After ingestion, the reduced form of coenzyme Q10, ubiquinol, predominates in the systemic circulation. Coenzyme Q10 is a potent antioxidant and may have a role in maintaining healthy muscle function, although the clinical significance of this effect is unknown. Reduced serum levels have been reported in Parkinson s disease. 

Derivatives of ubiquinones are antioxidants for foodstuffs and vitamins (qv) (217,218). Ubichromenol phosphates show antiinflammatory activity (219). Chromanol compounds inhibit oxidation of fats and can be used in treatment of macrocytic anemias (220). Monosulfate salts of 2,3-dimethoxy-5-methyl-6-substitutedhydroquinone have been reported to be inhibitors of lipid oxidation in rats (221). Polymers based on chloranilic and bromanilic acid have been prepared and contain oxygenated quinones (63), which are derived from 1,2,3,4-benzenetetrol (222). 

The body maintains an antioxidant network consisting of vitamins A, C, and E, antioxidant enzymes, and a group of related compounds called coenzyme Q, for which the general formula is shown. The n represents the number of times that a particular group is repeated it can be 6, 8, or 10. The coenzyme Q molecules are also called ubiquinones, because they are so ubiquitous in the body. Antioxidants are molecules that are easily oxidized and so react readily with radicals before the radicals can react with other compounds in the body. A variety of intricate mechanisms... 

Coenzyme Q10 (also known as ubiquinone or ubidecarenone), while not a herb, is a provitamin found in the mitochondria of plant and animal cells. It is involved in electron transport and may act as a free-radical scavenger, an antioxidant, or a membrane stabilizer. Coenzyme Q10 supplementation is primarily promoted as treating a variety of cardiovascular disorders, including the following ... 

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