ubiquinone and Iron-Overload

Iron overload (IOL) can cause hepatorenal damage due to iron-mediated oxidative and mitochondrial damage. Remarkably, combining a natural iron chelator with an antioxidant can exert greater efficacy than monotherapy. Thus, the present study aimed to evaluate the efficacy of Chia and CoQ

Topics: Animals; Antioxidants; Iron; Iron Chelating Agents; Iron Overload; Male; Mice; Oxidative Stress; Ubiquinone

This study investigated the anti-diabetic preventive activity of coenzyme Q10 (CoQ10) in a murine model of diet-induced insulin resistance (IR), Psammomys obesus (Po). IR was induced by feeding a standard laboratory diet (SD). CoQ10 oil suspension was orally administered at 10 mg/kg body weight (BW)/day along with SD for 9 months. Anthropometric parameters, namely, total body weight gain (BWG) and the relative weight of white adipose tissue (WAT) were determined. Blood glucose, insulin, quantitative insulin sensitivity check index (QUICKI), total antioxidant status (TAS), iron, malondialdehyde (MDA) and nitrite (NO2 (-)) were evaluated. NO2 (-) level was also assessed in peripheral blood mononuclear cells (PBMCs) culture supernatants. Our results show that CoQ10 supplementation significantly improved blood glucose, insulin, QUICKI, TAS, iron and MDA, but influenced neither NO2 (-) levels nor the anthropometric parameters. These findings support the hypothesis that CoQ10 would exert an anti-diabetic activity by improving both glycaemic control and antioxidant protection. The most marked effect of CoQ10 observed in this study concerns the regulation of iron levels, which may carry significant preventive importance.

Topics: Animals; Antioxidants; Dietary Supplements; Gerbillinae; Insulin Resistance; Iron Overload; Ubiquinone

This study describes the in vivo response of rat testes to acute iron overload. Male Wistar rats (250-300 g) were injected ip with iron dextran at doses of 250 (Fe250), 500 (Fe500), or 1000 mg/kg body wt (Fe1000) or with saline (C). Parameters of oxidative stress and iron toxicity were measured 20 h after injection. Total iron content was 3.5-, 5.3-, and 10.4-fold higher in the Fe250, Fe500, and Fe1000 groups, respectively, compared to controls (320 +/- 22 nmol/g tissue). Histological studies showed that: (a) iron accumulated in the sperm and other testes cells, and (b) spermatogenesis was markedly lower in the Fe1000 group. The concentration of alpha-tocopherol, ubiquinol-9, and ubiquinol-10 in the testes was inversely correlated with the extent of oxidation. Testes chemiluminescence was 45% higher in the Fe1000 group compared to controls (41 cps/cm(2)). Endogenous levels of lipid oxidation, evaluated as 2-thiobarbituric acid-reactive substances, were 46, 73, and 82% higher in the groups Fe250, Fe500, and Fe1000, respectively, than in controls (33.6 +/- 1.4 nmol/g tissue). Oxidative damage to DNA evaluated by the presence of 8-oxo-2'-deoxyguanosine (oxo(8)dG), was 26, 39, and 74% higher in the Fe250, Fe500, and Fe1000 groups, respectively, than in the C group (2.3 +/- 0.1 oxo(8)dG/10(5)dG). Protein oxidation was measured as protein thiols and carbonyl content in proteins and glutamine synthase activity. Protein thiols content and glutamine synthase activity were similar in all the groups, while the protein-associated carbonyls content was 96% higher in the Fe1000 group than in the C group (2.1 +/- 0.4 nmol/mg protein). No changes in the activities of superoxide dismutase, catalase, and glutathione peroxidase were observed. The results showed that in vivo iron overload induced oxidative stress and the impairment of spermatogenesis in rat testes that were dependent on the amount of iron supplemented and its accumulation in the tissue.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Deoxyguanosine; DNA; Iron; Iron Overload; Lipid Peroxidation; Luminescent Measurements; Male; Oxidative Stress; Proteins; Rats; Rats, Wistar; Testis; Thiobarbituric Acid Reactive Substances; Ubiquinone; Vitamin E

In order to examine whether iron and alcohol act synergistically during tumor initiation in vivo, we investigated the effects of dietary iron overload and a liquid ethanol-containing diet on the initiation phase of the Solt & Farber model of chemical hepatocarcinogenesis.. Following dietary supplementation with carbonyl iron for 8 weeks and ethanol pair-feeding according to Lieber deCarli for 5 weeks, animals were subjected to partial hepatectomy in order to induce regenerative cell proliferation and thereby "fix" putative DNA lesions. Levels of malondialdehyde, reduced and oxidized ubiquinone-9, alpha-tocopherol and 8-oxo-2'-deoxyguanosine were analyzed in liver tissue removed at the time of partial hepatectomy, and blood was collected for determination of alanine amino-transferase activities. Following a 2-week recovery period, promotion was achieved with 0.02% dietary 2-acetylaminofluorene and carbon tetrachloride. Two weeks after the completion of promotion, animals were sacrificed and the number of preneoplastic, glutathione S-transferase 7,7-positive lesions counted. Animals initiated with diethylnitrosamine served as a positive control group.. Serum aminotransferase activities were significantly increased, and hepatic contents of ubiquinol-9 (reduced ubiquinone-9) were significantly decreased in animals exposed to the combination of iron and ethanol in comparison to the other groups. Livers from iron-treated animals had decreased levels of alpha-tocopherol and increased contents of malondialdehyde, whereas treatment with ethanol did not further enhance these alterations. Levels of 8-oxo-2'-deoxyguanosine were not significantly different in animals treated with iron, ethanol or iron + ethanol as compared with controls. The number of preneoplastic foci at the time of sacrifice was not increased in livers exposed to iron and/or ethanol as compared with those from control animals. As expected, the number of foci was significantly increased in positive controls which were initiated with diethylnitrosamine.. Iron potentiated the cytotoxic effects of ethanol, resulting in increased serum aminotransferase activities and decreased hepatic contents of ubiquinol. However, the combination of iron and ethanol did not exert genotoxic effects detectable as enhanced hepatic levels of 8-oxo-2'-deoxyguanosine, or increased formation of preneoplastic, glutathione S-transferase 7,7-positive lesions in the Solt & Farber model of chemical hepatocarcinogenesis.

Topics: Alanine Transaminase; Animals; Antioxidants; Body Weight; Disease Models, Animal; Ethanol; Iron Overload; Liver; Liver Neoplasms, Experimental; Male; Malondialdehyde; Rats; Rats, Sprague-Dawley; Rats, Wistar; Ubiquinone; Vitamin E

The effect of dietary alpha-tocopherol (alpha-T) supplementation on iron overload-dependent oxidative damage was studied. Male Wistar rats were fed diets supplemented with 2.5% carbonyl iron and/or 200 mg/kg of alpha-tocopheryl acetate for 6 weeks. Oxidation of lipids and proteins were increased by iron overload in rat liver, and alpha-T dietary supplementation effectively prevented these effects. Iron overload decreased both, catalase and Mn-superoxide dismutase activities by 49 and 54%, respectively, with no effect on glutathione peroxidase activity. Alpha-T supplementation did not prevent the inhibition measured in catalase and Mn-superoxide dismutase activities. Iron dietary excess had no effect on liver alpha-T and ubiquinol 9 (UQ9) content. Ubiquinol 10 (UQ10) content after iron overload was decreased by 58 and 54% in whole liver and liver mitochondria, respectively. Alpha-T supplementation led to significant increases in alpha-T, UQ9 and UQ10 content in liver, as compared to control values, and partially prevented the decrease in UQ10 content due to iron excess. The results presented here indicate that initial stages of iron overload led to oxidative damage in liver (evaluated in terms of lipid and protein oxidation) with a decline in antioxidant defenses. alpha-T supplementation affected the liver content of lipid soluble antioxidants, suggesting a concerted antioxidant response at the cellular level to modulate the effect of excess iron availability.

Topics: Animals; Antioxidants; Catalase; Iron Overload; Lipid Peroxidation; Male; Rats; Rats, Wistar; Superoxide Dismutase; Ubiquinone; Vitamin E