**3.2 Insufficiency of CoQ10 levels are considered as one of the risk factors**

A significant lower level of CoQ10 is observed in cancerous tissues when compared to the normal tissues. CoQ10 is known for its counteraction of ROS in cellular and DNA integrity [30]. A case-control study [31, 32] revealed an inverse association between CoQ10 levels and incidence of breast cancer. An *in vitro* study with MCF-7 breast cancer cell lines where the cells were co-incubated with CoQ10 showed results with significant decrease in intracellular peroxide

formation and matrix metalloproteinase 2 activity and the effects were in a dosedependent manner [33].

Results further showed that CoQ10 had no inhibitory effect on apoptotic, anti-growth and anti-colonization effects of doxorubicin at any doses [34]. An animal study with mammary carcinoma model revealed that administration of CoQ10 at 40 mg/kg body weight restored the normal antioxidant level [35]. Reports suggest that increasing the dose of CoQ10 to 390 mg from 300 mg for more periods revealed resolution of tumor residue without any metastases [36–38] and increased the survivability [39]. Daily intake of a combination of 100 mg CoQ10, 10 mg riboflavin and 50 mg niacin reduced the circulating tumor markers [40–46]. Consuming a combination of CoQ10 along with lipotropic factor L-carnitine reduced the tumor-related fatigue in subjects [47–50].

#### **3.3 Coenzyme Q10 on ascites heart index (AHI) and ascites mortality**

In fast-growing broilers, the impact of ascites mortality is very high (after 5 weeks of age) as the farmers are not only losing the birds but also are incurring the feeding and rearing cost by the time. Feed restriction or skip-a-day feeding is followed in broiler during finisher phase to avoid the problem of ascites, which results in poor body weight and feed efficiency. Few researchers are suggesting that ascites might be due to the bird's inability to endogenously synthesize the CoQ10 demand. To counteract this, CoQ10 was used, and in fact, the importance of CoQ10 was felt with a reduction in ascites mortality in broilers when fed with CoQ10 [51]. Then, the term ascites heart index (AHI) comes into prominence, which gives more information about the susceptibility of the birds to ascites. Ascites heart index (AHI), a sensitive index of pulmonary hypertension, is based on the relative ratio of the right ventricle to the total ventricle [52]. The AHI was further made into a more useful tool where broilers with AHI value of less than 0.27 without any fluid accumulation in abdomen are normal and those birds having AHI value more than 0.30 with fluid accumulation are pulmonary hypertensioned and prone to ascites mortality [53]. The relative heart weight of birds receiving CoQ10 at 20 mg kgG1 of diet was higher [54–58]. A reduction in AHI ratio in broilers fed with CoQ10 at 40 mg/kg of feed was noticed [59]. However, there was a lower heart weight with respect to percentage of body weight when broilers fed with 20 and 40 mg of CoQ10 [60]. Ascites mortality in broilers was reduced around 75% by CoQ10 supplementation at both 20 and 40 mg/kg of diet. But at 40 mg/kg of diet supplementation, the incidence of leg problem was high. This reduction in ascites mortality (around 40%) was observed when broilers were fed CoQ9. These studies imply that CoQ, either 9 or 10 isoprene units, is able to reduce the broiler's mortality due to ascites.

#### **3.4 Coenzyme Q10 on lipid metabolism**

Clinical human and animal studies suggested that dietary CoQ10 supplementation improved the cholesterol metabolism in mammals. Nearly 10% lower cholesterol concentration was found in heart tissue of broilers when supplemented with CoQ10 [8]. CoQ10 supplementation decreased plasma total cholesterol concentration in humans [61] and rats [62]. CoQ10 was reportedly able to suppress the hepatic cholesterogenesis in rats [63] and in hens [64]. In an experiment in layer, chicks revealed reduced hepatic total cholesterol, plasma cholesterol and very low density lipoprotein (VLDL) cholesterol concentration by supplementation of CoQ10 at 400 and 800 mg/kg feed [65]. However, the plasma HDL, LDL cholesterol and total bile acids were not influenced by CoQ10 supplementation. The reduction in cholesterol level was due to decreased enzymatic activity of

**187**

dria by CoQ10.

*Coenzyme Q10: Regulators of Mitochondria and beyond DOI: http://dx.doi.org/10.5772/intechopen.89496*

concentration by 7–10% on CoQ10 supplementation.

**3.5 Coenzyme Q10 antioxidant properties**

3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) in the liver, but it had no influence on the enzymatic activity of 3-hydroxy-3-methylglutaryl coenzyme A synthetase (HMGS). Dietary CoQ10 supplementation suppressed hepatic cholesterogenesis in laying hens [64] and observed a decrease in egg yolk cholesterol

In a long-term CoQ10 feeding trial, reduced cholesterol synthesis with suppression in cholesterol catabolism was observed resulting in return of hepatic cholesterol to normal level [65]. However, long-term (0–42 days) supplementation of CoQ10 at 20 and 40 mg kgG1 reduced the levels of serum total cholesterol and serum LDL cholesterol [58, 66]. The reduction in serum LDL cholesterol due to CoQ10 supplementation was attributed to the action of reduced form of CoQ10(H2), which induces characteristic gene expression patterns, which are translated into reduced LDL cholesterol level in human subjects. However, there were no reports of increase in the HDL cholesterol levels [58, 65]. CoQ10 reduced cholesterol metabolism in the plasma of patients with myocardial infarction [67] and in diabetic rats [62]. CoQ9, a major coenzyme Q in rats, decreases plasma total

cholesterol concentration and suppresses hepatic cholesterogenesis [68].

Under the present intensive system of poultry production especially in tropics, stresses due to environment, metabolic, managemental, etc. are inevitable, resulting in lower productivity, less nutrient retention, decreased serum and tissue vitamin level, humoral immunity (HI) and molecular changes like protein, nucleic acid denaturation and lipid peroxidation. Increased reactive oxygen species (ROS) metabolites compromise cell membrane integrity [53], which results in drip loss in muscles [60] affect keeping quality of muscles. Different nutrients and additives (like the use of synthetic amino acids, low heat increment nutrients, vitamins C, E and minerals such as selenium, zinc and magnesium or additive such as genistein and melatonin, and essential oils) are tried with varied success to counteract these stresses [69]. Aside from its role in mitochondrial bioenergetics, ubiquinone also affects membrane fluidity [11] and protects membrane phospholipids against peroxidation [12]. CoQ10 in its reduced form possesses free radical scavenging and increases total antioxidant capacity [70, 71]. CoQ10 is preferred over α-tocopherol [72] as CoQ10 enhances the activity of other enzymatic and non-enzymatic antioxidants. The serum vitamin E level was increased by CoQ10 at 20 mg/kg [7, 58]. CoQ10 shows the property of regenerating the oxidized (inactive) α-tocopherol to reduce (an active form of vitamin E) [73]. Serum or liver malondialdehyde (MDA) is a product of lipid peroxidation and serves as a biomarker for oxidative damage in lipids. This suggested the protective action on lipid peroxidation in liver mitochon-

Superoxide dismutase (SOD) activity was increased in accordance with CoQ10

supplementation in broilers and in rats [74]. An increase in hepatic SOD and anti-ROS capacity in broilers was observed by CoQ10 supplementation [55]. The supplementation of CoQ10 increases the SOD activity by antagonizing nitric oxide (NO) inactivation, thereby making more NO availability for the biological function that leads to extracellular SOD gene expression. The reduced glutathione and glutathione peroxidase activity was also increased by CoQ10 at 20 mg/kg. This synergistic action of CoQ10 is possible as it acts as a primary regenerating antioxidant [75]. However, supplementation at 40 mg kgG1 of diet resulted in no effect on serum vitamin E and SOD levels. This ineffectiveness of CoQ10 at 40 mg kgG1 of diet is due to the auto-oxidation of CoQ10 resulting in higher production of mitochondrial reactive oxygen species (ROS), which leads to oxidative

*Coenzyme Q10: Regulators of Mitochondria and beyond DOI: http://dx.doi.org/10.5772/intechopen.89496*

*Apolipoproteins, Triglycerides and Cholesterol*

reduced the tumor-related fatigue in subjects [47–50].

units, is able to reduce the broiler's mortality due to ascites.

Clinical human and animal studies suggested that dietary CoQ10 supplementation improved the cholesterol metabolism in mammals. Nearly 10% lower cholesterol concentration was found in heart tissue of broilers when supplemented with CoQ10 [8]. CoQ10 supplementation decreased plasma total cholesterol concentration in humans [61] and rats [62]. CoQ10 was reportedly able to suppress the hepatic cholesterogenesis in rats [63] and in hens [64]. In an experiment in layer, chicks revealed reduced hepatic total cholesterol, plasma cholesterol and very low density lipoprotein (VLDL) cholesterol concentration by supplementation of CoQ10 at 400 and 800 mg/kg feed [65]. However, the plasma HDL, LDL cholesterol and total bile acids were not influenced by CoQ10 supplementation. The reduction in cholesterol level was due to decreased enzymatic activity of

**3.4 Coenzyme Q10 on lipid metabolism**

dependent manner [33].

formation and matrix metalloproteinase 2 activity and the effects were in a dose-

Results further showed that CoQ10 had no inhibitory effect on apoptotic, anti-growth and anti-colonization effects of doxorubicin at any doses [34]. An animal study with mammary carcinoma model revealed that administration of CoQ10 at 40 mg/kg body weight restored the normal antioxidant level [35]. Reports suggest that increasing the dose of CoQ10 to 390 mg from 300 mg for more periods revealed resolution of tumor residue without any metastases [36–38] and increased the survivability [39]. Daily intake of a combination of 100 mg CoQ10, 10 mg riboflavin and 50 mg niacin reduced the circulating tumor markers [40–46]. Consuming a combination of CoQ10 along with lipotropic factor L-carnitine

**3.3 Coenzyme Q10 on ascites heart index (AHI) and ascites mortality**

In fast-growing broilers, the impact of ascites mortality is very high (after 5 weeks of age) as the farmers are not only losing the birds but also are incurring the feeding and rearing cost by the time. Feed restriction or skip-a-day feeding is followed in broiler during finisher phase to avoid the problem of ascites, which results in poor body weight and feed efficiency. Few researchers are suggesting that ascites might be due to the bird's inability to endogenously synthesize the CoQ10 demand. To counteract this, CoQ10 was used, and in fact, the importance of CoQ10 was felt with a reduction in ascites mortality in broilers when fed with CoQ10 [51]. Then, the term ascites heart index (AHI) comes into prominence, which gives more information about the susceptibility of the birds to ascites. Ascites heart index (AHI), a sensitive index of pulmonary hypertension, is based on the relative ratio of the right ventricle to the total ventricle [52]. The AHI was further made into a more useful tool where broilers with AHI value of less than 0.27 without any fluid accumulation in abdomen are normal and those birds having AHI value more than 0.30 with fluid accumulation are pulmonary hypertensioned and prone to ascites mortality [53]. The relative heart weight of birds receiving CoQ10 at 20 mg kgG1 of diet was higher [54–58]. A reduction in AHI ratio in broilers fed with CoQ10 at 40 mg/kg of feed was noticed [59]. However, there was a lower heart weight with respect to percentage of body weight when broilers fed with 20 and 40 mg of CoQ10 [60]. Ascites mortality in broilers was reduced around 75% by CoQ10 supplementation at both 20 and 40 mg/kg of diet. But at 40 mg/kg of diet supplementation, the incidence of leg problem was high. This reduction in ascites mortality (around 40%) was observed when broilers were fed CoQ9. These studies imply that CoQ, either 9 or 10 isoprene

**186**

3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) in the liver, but it had no influence on the enzymatic activity of 3-hydroxy-3-methylglutaryl coenzyme A synthetase (HMGS). Dietary CoQ10 supplementation suppressed hepatic cholesterogenesis in laying hens [64] and observed a decrease in egg yolk cholesterol concentration by 7–10% on CoQ10 supplementation.

In a long-term CoQ10 feeding trial, reduced cholesterol synthesis with suppression in cholesterol catabolism was observed resulting in return of hepatic cholesterol to normal level [65]. However, long-term (0–42 days) supplementation of CoQ10 at 20 and 40 mg kgG1 reduced the levels of serum total cholesterol and serum LDL cholesterol [58, 66]. The reduction in serum LDL cholesterol due to CoQ10 supplementation was attributed to the action of reduced form of CoQ10(H2), which induces characteristic gene expression patterns, which are translated into reduced LDL cholesterol level in human subjects. However, there were no reports of increase in the HDL cholesterol levels [58, 65]. CoQ10 reduced cholesterol metabolism in the plasma of patients with myocardial infarction [67] and in diabetic rats [62]. CoQ9, a major coenzyme Q in rats, decreases plasma total cholesterol concentration and suppresses hepatic cholesterogenesis [68].

#### **3.5 Coenzyme Q10 antioxidant properties**

Under the present intensive system of poultry production especially in tropics, stresses due to environment, metabolic, managemental, etc. are inevitable, resulting in lower productivity, less nutrient retention, decreased serum and tissue vitamin level, humoral immunity (HI) and molecular changes like protein, nucleic acid denaturation and lipid peroxidation. Increased reactive oxygen species (ROS) metabolites compromise cell membrane integrity [53], which results in drip loss in muscles [60] affect keeping quality of muscles. Different nutrients and additives (like the use of synthetic amino acids, low heat increment nutrients, vitamins C, E and minerals such as selenium, zinc and magnesium or additive such as genistein and melatonin, and essential oils) are tried with varied success to counteract these stresses [69]. Aside from its role in mitochondrial bioenergetics, ubiquinone also affects membrane fluidity [11] and protects membrane phospholipids against peroxidation [12]. CoQ10 in its reduced form possesses free radical scavenging and increases total antioxidant capacity [70, 71]. CoQ10 is preferred over α-tocopherol [72] as CoQ10 enhances the activity of other enzymatic and non-enzymatic antioxidants. The serum vitamin E level was increased by CoQ10 at 20 mg/kg [7, 58]. CoQ10 shows the property of regenerating the oxidized (inactive) α-tocopherol to reduce (an active form of vitamin E) [73]. Serum or liver malondialdehyde (MDA) is a product of lipid peroxidation and serves as a biomarker for oxidative damage in lipids. This suggested the protective action on lipid peroxidation in liver mitochondria by CoQ10.

Superoxide dismutase (SOD) activity was increased in accordance with CoQ10 supplementation in broilers and in rats [74]. An increase in hepatic SOD and anti-ROS capacity in broilers was observed by CoQ10 supplementation [55]. The supplementation of CoQ10 increases the SOD activity by antagonizing nitric oxide (NO) inactivation, thereby making more NO availability for the biological function that leads to extracellular SOD gene expression. The reduced glutathione and glutathione peroxidase activity was also increased by CoQ10 at 20 mg/kg. This synergistic action of CoQ10 is possible as it acts as a primary regenerating antioxidant [75]. However, supplementation at 40 mg kgG1 of diet resulted in no effect on serum vitamin E and SOD levels. This ineffectiveness of CoQ10 at 40 mg kgG1 of diet is due to the auto-oxidation of CoQ10 resulting in higher production of mitochondrial reactive oxygen species (ROS), which leads to oxidative

stress in the body. The development of auto-oxidation was observed in birds fed higher level of CoQ10 for prolonged duration.
