ubiquinone-q2 and Disease-Models--Animal

Coenzyme Q10 (CoQ10), also known as ubiquinone, is a fat-soluble antioxidant. Although CoQ10 has not been approved as medication by the Food and Drug Administration, it is widely used in dietary supplements. Some studies have shown that CoQ10 has anti-inflammatory effects on various autoimmune disorders. In this study, we investigated the anti-inflammatory effects of liposome/gold hybrid nanoparticles encoded with CoQ10 (LGNP-CoQ10). Both CoQ10 and LGNP-CoQ10 were administered orally to mice with collagen-induced arthritis (CIA) for 10 weeks. The inflammation pathology of joint tissues of CIA mice was then analyzed using hematoxylin and eosin and Safranin O staining, as well as immunohistochemistry analysis. We obtained immunofluorescence staining images of spleen tissues using confocal microscopy. We found that pro-inflammatory cytokines were significantly decreased in LGNP-CoQ10 injected mice. Th17 cell and phosphorylated STAT3-expressed cell populations were also decreased in LGNP-CoQ10 injected mice. When human peripheral blood mononuclear cells (PBMCs) were treated with CoQ10 and LGNP-CoQ10, the IL-17 expression of PBMCs in the LGNP-CoQ10-treated group was significantly reduced. Together, these results suggest that LGNP-CoQ10 has therapeutic potential for the treatment of rheumatoid arthritis.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Arthritis, Experimental; Arthritis, Rheumatoid; Autoimmune Diseases; Cell Line; Cytokines; Disease Models, Animal; Gold; Humans; Inflammation; Interleukin-17; Leukocytes, Mononuclear; Liposomes; Male; Metal Nanoparticles; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; STAT3 Transcription Factor; T-Lymphocytes, Regulatory; Th17 Cells; Ubiquinone

Primary disorders of the human coenzyme Q

Topics: Animals; Apoptosis; Ataxia; Biosynthetic Pathways; Cytochrome P-450 Enzyme System; Disease Models, Animal; Humans; Hydroxybenzoates; Mice; Mitochondria; Mitochondrial Diseases; Muscle Weakness; Pyrimidines; Solubility; Treatment Outcome; Ubiquinone; Vitamins

The purpose of this study was to compare the effects of thymoquinone and icodextrin in rats within the framework of an experimental adhesion model.. Rats were separated into three groups: (1) a control group consisting of rats that had 2 ml of isotonic solution administered intraperitoneally, (2) an ICO group administered with 2 ml of 4% icodextrin, and (3) a TQ group administered thymoquinone (10 mg/kg), all following cecal abrasion. The three groups underwent a reoperation on the 7th postoperative day. Hydroxyproline levels were analyzed in the resected adhesive tissues, and histopathological investigations were conducted. Blood samples were collected for biochemical analyses.. Fewer postoperative adhesions were observed in the ICO and TQ groups compared with the control group. A comparison of the TQ and ICO groups revealed lowers levels of postoperative adhesions in the TQ group. Compared with the control group, malondialdehyde, 8-OH-deoxyguanosine/deoxyguanosine (8-OHdG/10dG), Coenzyme Q10 (CoQ10), and CoenzymeQ10/reduced CoenzymeQ10 (CoQ10/CoQ10H) values were found to be lower in the TQ and ICO groups. When the TQ and ICO groups were compared with respect to their biochemical parameters, the results for all of the four parameters were found to be statistically significantly lower in the TQ group (P < 0.000). The levels of hydroxyproline in the control, ICO, and TQ groups were found to be (mean ± standard deviation) 502.25 ± 90.39 μg/g, 342.13 ± 66.61 μg/g, and 287.88 ± 49.59 μg/g, respectively.. A comparison of the antiadhesive effects of thymoquinone and icodextrin revealed thymoquinone to be more effective. These results indicate that thymoquinone is an efficient and strong antiadhesive molecule.

Topics: Animals; Benzoquinones; Disease Models, Animal; Glucans; Glucose; Humans; Icodextrin; Injections, Intraperitoneal; Male; Postoperative Complications; Rats; Rats, Wistar; Tissue Adhesions; Ubiquinone

Obesity is a major risk factor for the onset of type 2 diabetes; however, little is known about the gene(s) involved. Therefore, we developed new animal models of obesity to search for diabetogenic genes associated with obesity. We generated double congenic rat strains with a hyperglycaemic quantitative trait locus (QTL) derived from the Otsuka Long-Evans Tokushima Fatty rat and a fa/fa (Lepr-/-) locus derived from the Zucker Fatty rat; phenotypic analysis for plasma glucose and insulin levels and RNA and protein levels were determined using reverse transcription quantitative PCR and Western blotting analyses, respectively. The double congenic strain F344-fa-nidd2 (Lepr-/- and Nidd2/of) exhibited significantly higher glucose levels and significantly lower hypoglycaemic response to insulin than the obese control strain F344-fa (Lepr-/-). These phenotypes were clearly observed in the obese strains but not in the lean strains. These results indicate that the Nidd2/of locus harbours a diabetogenic gene associated with obesity. We measured the expression of 60 genes in the Nidd2/of QTL region between the strains and found that the mRNA expression levels of five genes were significantly different between the strains under the condition of obesity. However, three of the five genes were differentially expressed in both obese and lean rats, indicating that these genes are not specific for the condition of obesity. Conversely, the other two genes, coenzyme Q2 (Coq2) and placenta-specific 8 (Plac8), were differentially expressed only in the obese rats, suggesting that these two genes are candidates for the onset of type 2 diabetes associated with obesity in rats.

Topics: Animals; Base Sequence; Body Weight; Diabetes Mellitus, Type 2; Disease Models, Animal; Gene Expression; Genetic Association Studies; Genetic Predisposition to Disease; Liver; Male; Obesity; Pregnancy Proteins; Quantitative Trait Loci; Rats, Inbred F344; Sequence Analysis, DNA; Ubiquinone

Ubiquinone (UQ), a.k.a. coenzyme Q, is a redox-active lipid that participates in several cellular processes, in particular mitochondrial electron transport. Primary UQ deficiency is a rare but severely debilitating condition. Mclk1 (a.k.a. Coq7) encodes a conserved mitochondrial enzyme that is necessary for UQ biosynthesis. We engineered conditional Mclk1 knockout models to study pathogenic effects of UQ deficiency and to assess potential therapeutic agents for the treatment of UQ deficiencies. We found that Mclk1 knockout cells are viable in the total absence of UQ. The UQ biosynthetic precursor DMQ9 accumulates in these cells and can sustain mitochondrial respiration, albeit inefficiently. We demonstrated that efficient rescue of the respiratory deficiency in UQ-deficient cells by UQ analogues is side chain length dependent, and that classical UQ analogues with alkyl side chains such as idebenone and decylUQ are inefficient in comparison with analogues with isoprenoid side chains. Furthermore, Vitamin K2, which has an isoprenoid side chain, and has been proposed to be a mitochondrial electron carrier, had no efficacy on UQ-deficient mouse cells. In our model with liver-specific loss of Mclk1, a large depletion of UQ in hepatocytes caused only a mild impairment of respiratory chain function and no gross abnormalities. In conjunction with previous findings, this surprisingly small effect of UQ depletion indicates a nonlinear dependence of mitochondrial respiratory capacity on UQ content. With this model, we also showed that diet-derived UQ10 is able to functionally rescue the electron transport deficit due to severe endogenous UQ deficiency in the liver, an organ capable of absorbing exogenous UQ.

Topics: Alleles; Animals; Ataxia; Cell Respiration; Cell Survival; Disease Models, Animal; Electron Transport; Liver; Membrane Proteins; Mice; Mice, Knockout; Mitochondria; Mitochondrial Diseases; Mitochondrial Proteins; Mixed Function Oxygenases; Muscle Weakness; Oxygen Consumption; Ubiquinone; Vitamin K 2

Oxidative modification of lipoproteins may trigger and maintain atherogenesis. We compared the effects of different antioxidants (alpha-tocopherol, probucol, ubiquinone-10) at doses similar to those used in humans in Watanabe Heritable Hyperlipidemic (WHHL) rabbits for 12 months. Aortic lesions were analyzed for their extent and cellular composition of lesions, mean thickness of fibrous caps and density of smooth muscle cells therein, content of antioxidants, non-oxidized and oxidized lipids. Compared to controls, probucol significantly lowered the extent and macrophage content of lesions and increased the existence and smooth muscle cell density of fibrous caps. alpha-Tocopherol supplementation increased the aortic content of vitamin E, but had no decreasing effect on either the accumulation of macrophage-specific antigen in the aorta or lesion size. Nevertheless, both probucol and alpha-tocopherol significantly decreased in vitro LDL oxidizability, measured under typically strong oxidative conditions. Ubiquinone-10 supplement increased lesion size and the fraction of lesions containing fibrous caps; however, LDL oxidizability remained unaffected by ubiquinone-10 treatment. None of the antioxidants tested lowered oxidized lipids within aortic tissue; however, long-term treatment with probucol provided the most effective anti-atherosclerotic effect, while alpha-tocopherol may be pro-atherogenic and ubiquinone-10 exerts ambivalent effects. Our data suggest that (i) widely used oxidation measures, such as ex-vivo LDL oxidizability, do not reflect the degree of atherosclerosis; and (ii) long-term beneficial effects of relatively low doses of antioxidants may be outweighed by high levels of plasma cholesterol in WHHL rabbits.

Topics: alpha-Tocopherol; Animals; Antioxidants; Aorta; Arteriosclerosis; Coenzymes; Disease Models, Animal; Female; Humans; Lipids; Lipoproteins, LDL; Male; Probucol; Rabbits; Ubiquinone; Vitamin E

It has been shown that prophylactic administration of ubiquinone protects rats liver from the toxic damage by D-galactosamine both on ultrastructural and on cell levels. Ubiquinone administration prevents necrosis in hepatocytes and preserves their ability for compensatory reactions expressed in activation of protein-synthesis regulating structures in the cell. Ubiquinone decreases hyperfermentemia and hyperbilirubinemia as well as prevents the decrease in liver protein content caused by galactosamine. Ubiquinone exerts an antioxidant effect, blocking the induction of lipid peroxidation both in intact and hepatic rats.

Topics: Animals; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Drug Evaluation, Preclinical; Galactosamine; Liver; Male; Microscopy, Electron; Rats; Ubiquinone