**2.1 The protective properties of coenzyme Q**

Chronic inflammation, systemic OS, and mitochondrial dysfunction are the main factors which participate in etiopathogenesis of arthritis. Mitochondria play a central role in ATP formation in the respiratory chain (**Figure 2**) and in maintaining redox homeostasis. OS processes are activated under pathological conditions. Oxidative damage of mitochondria may lead to the dysfunction of the respiratory chain which further increases ROS formation. Thus, mitochondrial dysfunction can contribute to the development of inflammatory human diseases [16].

The therapy of RA is an actual problem in clinical rheumatology due to the toxicity and side effects of antirheumatic drugs; therefore, new treatment options are being sought. Methotrexate (MTX), used in the treatment of RA, can induce hepatocellular injury. In combination with coenzyme Q10, anti-arthritic effect of MTX was potentiated, and hepatotoxicity was suppressed [17]. Preservation of mitochondrial function could reduce OS and may represent a novel therapeutic approach in patients with inflammatory diseases. Progressive muscle atrophy and inflammatory myopathy in RA have been proposed to be mediated by disturbances of myofibrils and mitochondria [18]. Due to the unique properties, coenzyme Q10 (CoQ10) can serve as a useful adjuvant in the management of arthritis. CoQ10

**153**

**Figure 4.**

**Figure 3.**

*Chemical structure of coenzyme Q.*

*The Role of Endogenous Antioxidants in the Treatment of Experimental Arthritis*

in humans is CoQ10, in rats' coenzyme Q9 (CoQ9) (**Figure 3**).

tocopherol (αT) and gamma-tocopherol (γT) (**Figure 4**).

CoQ exerts its antioxidant function either directly on superoxide radicals or indirectly on lipid radicals, both singly and in cooperation with vitamin E [29]. Beneficial antioxidant and anti-inflammatory properties of CoQ10 were proved in RA patients [30]. Tocopherols are the subgroup of vitamin E, occurring in isomers α, β, γ, and δ. All tocopherols are potent antioxidants with lipoperoxyl radicalscavenging activities [31]. The main forms of tocopherols in humans are alpha-

The most significant difference in metabolism of αT and γT is preferential binding of αT by α-TTP (α-tocopherol transfer protein). The γT is metabolized mainly through cytochrome P450, and formed hydrophilic metabolites are excreted in urine [32]. Isoforms of vitamin E differentially regulate inflammation [33]. In contrast to αT, γT reacts with nitrogen radicals which are formed extensively in inflammatory diseases such as RA. Vitamin E has a potential role in skeletal muscle health, in regulation of OS and inflammation [34]. Low levels of vitamin E and

*Chemical structure of tocopherols. α-tocopherol: R1 = CH3; R2 = CH3; γ-tocopherol: R1 = H; R2 = CH3.*

is irreplaceable in mitochondrial bioenergetics; it participates as a cofactor of dehydrogenases in the transport of electrons and protons as well as in ATP production [19]. The respiratory chain located in the inner mitochondrial membrane is organized into five complexes (I, II, III, IV, and V). The transport of electrons from NADH and FADH2 and production of electrochemical potential and proton gradients are necessary for the synthesis of ATP [20, 21]. Electrons are carried out from complexes I and II to complex III by coenzyme Q (CoQ ). It has been demonstrated that lipoperoxidation is accompanied by reduced mitochondrial CoQ concentrations concomitantly with the decreased activities of respiratory chain enzymes, such as NADH- and succinate oxidases [22–24]. Increased levels of antioxidants have also been reported including CoQ in tissues as well as activities of antioxidant enzymes in experimental models of diseases associated with increased free radicals' generation such as diabetes mellitus [25–27]. The term "redox signaling" has been introduced to describe a regulatory process in which protective responses against oxidative damage are induced to reset the oxidant-antioxidant balance [28]. CoQ (ubiquinone) is the only lipophilic antioxidant to be biosynthesized; the main form

*DOI: http://dx.doi.org/10.5772/intechopen.85568*

**Figure 2.** *Function of coenzyme Q in mitochondrial respiratory chain. With permission of [15].*

#### *The Role of Endogenous Antioxidants in the Treatment of Experimental Arthritis DOI: http://dx.doi.org/10.5772/intechopen.85568*

is irreplaceable in mitochondrial bioenergetics; it participates as a cofactor of dehydrogenases in the transport of electrons and protons as well as in ATP production [19]. The respiratory chain located in the inner mitochondrial membrane is organized into five complexes (I, II, III, IV, and V). The transport of electrons from NADH and FADH2 and production of electrochemical potential and proton gradients are necessary for the synthesis of ATP [20, 21]. Electrons are carried out from complexes I and II to complex III by coenzyme Q (CoQ ). It has been demonstrated that lipoperoxidation is accompanied by reduced mitochondrial CoQ concentrations concomitantly with the decreased activities of respiratory chain enzymes, such as NADH- and succinate oxidases [22–24]. Increased levels of antioxidants have also been reported including CoQ in tissues as well as activities of antioxidant enzymes in experimental models of diseases associated with increased free radicals' generation such as diabetes mellitus [25–27]. The term "redox signaling" has been introduced to describe a regulatory process in which protective responses against oxidative damage are induced to reset the oxidant-antioxidant balance [28]. CoQ (ubiquinone) is the only lipophilic antioxidant to be biosynthesized; the main form in humans is CoQ10, in rats' coenzyme Q9 (CoQ9) (**Figure 3**).

CoQ exerts its antioxidant function either directly on superoxide radicals or indirectly on lipid radicals, both singly and in cooperation with vitamin E [29]. Beneficial antioxidant and anti-inflammatory properties of CoQ10 were proved in RA patients [30]. Tocopherols are the subgroup of vitamin E, occurring in isomers α, β, γ, and δ. All tocopherols are potent antioxidants with lipoperoxyl radicalscavenging activities [31]. The main forms of tocopherols in humans are alphatocopherol (αT) and gamma-tocopherol (γT) (**Figure 4**).

The most significant difference in metabolism of αT and γT is preferential binding of αT by α-TTP (α-tocopherol transfer protein). The γT is metabolized mainly through cytochrome P450, and formed hydrophilic metabolites are excreted in urine [32]. Isoforms of vitamin E differentially regulate inflammation [33]. In contrast to αT, γT reacts with nitrogen radicals which are formed extensively in inflammatory diseases such as RA. Vitamin E has a potential role in skeletal muscle health, in regulation of OS and inflammation [34]. Low levels of vitamin E and

**Figure 3.** *Chemical structure of coenzyme Q.*

**Figure 4.** *Chemical structure of tocopherols. α-tocopherol: R1 = CH3; R2 = CH3; γ-tocopherol: R1 = H; R2 = CH3.*

*Antioxidants*

**arthritis**

**2.1 The protective properties of coenzyme Q**

can be divided into true scavengers, metal-buffering proteins, and chelators of redox-stable metals [13]. This chapter is focused on evaluating coenzyme Q10 and hyaluronan of different molecular weight in experimental arthritis induced in rats.

**2. Coenzyme Q10 supplementation and its contribution to therapy of** 

Chronic inflammation, systemic OS, and mitochondrial dysfunction are the main factors which participate in etiopathogenesis of arthritis. Mitochondria play a central role in ATP formation in the respiratory chain (**Figure 2**) and in maintaining redox homeostasis. OS processes are activated under pathological conditions. Oxidative damage of mitochondria may lead to the dysfunction of the respiratory chain which further increases ROS formation. Thus, mitochondrial dysfunction can

The therapy of RA is an actual problem in clinical rheumatology due to the toxicity and side effects of antirheumatic drugs; therefore, new treatment options are being sought. Methotrexate (MTX), used in the treatment of RA, can induce hepatocellular injury. In combination with coenzyme Q10, anti-arthritic effect of MTX was potentiated, and hepatotoxicity was suppressed [17]. Preservation of mitochondrial function could reduce OS and may represent a novel therapeutic approach in patients with inflammatory diseases. Progressive muscle atrophy and inflammatory myopathy in RA have been proposed to be mediated by disturbances of myofibrils and mitochondria [18]. Due to the unique properties, coenzyme Q10 (CoQ10) can serve as a useful adjuvant in the management of arthritis. CoQ10

contribute to the development of inflammatory human diseases [16].

*Function of coenzyme Q in mitochondrial respiratory chain. With permission of [15].*

**152**

**Figure 2.**

other endogenous antioxidants have been considered as a risk factor for the development of RA [35]. We hypothesized that administration of CoQ10 could affect inflammation in arthritic rats by regulating the endogenous antioxidants and OS.
