Effect of Coenzyme Q10 on Th1/Th2 Paradigm in Females with Idiopathic Recurrent Pregnancy Loss.

PROBLEM: Recurrent pregnancy loss is characterized by predominant Th1-type immunity and increased reactive oxygen species. Low levels of Coenzyme Q10 are found in the plasma of RPL as compared to healthy pregnant females. Our aim was to investigate whether in vitro supplementation of PBMCs from such females with CoQ10 could change the observed Th1 bias. METHOD OF STUDY: PBMCs were isolated from 20 RPL pregnant and non-pregnant females and 16 healthy pregnant females and incubated with CoQ10 in in vitro conditions. Phenotyping of Th1, Th2, and Th17 cells was performed by flow cytometry. Cytokine levels were determined by ELISA. RESULTS: PBMCs treated with CoQ10 showed significantly decreased percentage of Th1 cells (P < 0.005) in pregnant females with history of RPL than in the untreated ones. Also, levels of IFN-γ and TNF-α were significantly decreased in the culture supernatant of treated PBMCs from RPL. DCFDA staining showed significantly reduced production of ROS in the treated PBMCs in RPL females. CONCLUSION: CoQ10 was effective in maintaining the immune homeostasis by reducing the proportion of IFN-γ-producing T cells and proinflammatory cytokine levels in the RPL pregnant females. This property could be attributed to the capability of CoQ10 in reducing oxidative stress by decreasing ROS production.

Coenzyme Q10 and immunity: A case report and new implications for treatment of recurrent infections in metabolic diseases.

Coenzyme Q10 (CoQ10) deficiency can manifest diversely, from isolated myopathy to multisystem involvement. Immune dysregulation has not been reported as a feature of the disease. We report a four-year old girl with failure to thrive, recurrent infections, developmental delay with hypotonia, and CoQ10 deficiency with impaired immune function, which improved after CoQ10 and immunoglobulin replacement therapy. Immune dysfunction in CoQ10 deficiency should be considered and treated appropriately.

The qualitative effects of resveratrol and coenzyme Q10 administration on the gluteus complex muscle morphology of SJL/J mice with dysferlinopathy / Efectos cualitativos de la administración de resveratrol y coenzima Q10 en la morfología del complejo muscular glúteo de ratones SJL/J con disferlinopatía

Dysferlinopathy is a form of muscular dystrophy affecting muscles of the shoulder and pelvic girdles, resulting from inheritance of a mutated dysferlin gene. The encoded dysferlin protein is proposed to be involved in sarcolemmal vesicle fusion with a disrupted plasma membrane; however, with defective protein function these vesicles accumulate beneath the disruption site but are unable to fuse with it and reseal the membrane, thus rendering the membrane repair mechanism defective. The SJL/J mouse model presents with characteristics much like the commonest human condition. Immune modulators have long been under study in the maintenance of muscle health in muscular dystrophies. Such supplementary treatment would ideally suppress inflammation, preventing the immune response toward degenerating muscle from causing additional muscle fiber death, and thus provide a mechanism by which to prolong the life of muscle fibers with inherently defective healing apparatus. For this purpose the anti-inflammatory supplement resveratrol and the membrane-protective supplement coenzyme Q10 were administered separately and in combination to experimental animals to determine their effectiveness in possible therapy of dysferlinopathy. The findings of this study report that low doses of resveratrol and coenzyme Q10 supplementation in exclusivity were unable to afford much protection to muscle fibers at the tissue level. High doses of coenzyme Q10 proved more effective in reducing attenuating inflammation; and combination treatment with resveratrol and coenzyme Q10 provided not only the membrane-protective effects of coenzyme Q10, but also the anti-inflammatory effects of resveratrol which failed to materialize at sufficient levels in exclusive administration.

Disferlinopatía es una forma de distrofia muscular que afecta a los músculos de los hombros y cintura pélvica, resultado de la herencia y mutación del gen de la distrofina. Sugerimos que la proteína codificada distrofina que integra la estructura sarcolemal con una membrana plasmática interrumpida, que al presentar una proteína defectuosa, las estructuras se acumulan debajo del sitio de alteración sin lograr fundirse con éste y cerrar la membrana afectando el mecanismo de reparación. El modelo de ratón SJL / J se presenta con características muy similares a una condición humana común. Los inmunomoduladores han sido objeto de estudio en el mantenimiento de la salud muscular en las distrofias musculares. Este tipo de tratamiento suplementario puede ser ideal para suprimir la inflamación, en la prevención de la respuesta inmune en la degeneración muscular causando la muerte adicional de fibra muscular, y al mismo tiempo proporcionar, un mecanismo con el cual prolongar la vida útil de aquellas fibras musculares con el aparato de sanación comprometido. Para ello, el Resveratrol suplemento anti-inflamatorio y el suplemento protector de membrana coenzima Q10 se administró por separado y en combinación en los animales de laboratorio para determinar su efectividad en el tratamiento de posible disferlinopatía. Los resultados de este estudio indican que el Resveratrol en menor dosis y la coenzima Q 10 administrados como suplementos de manera exclusiva, no demostraron efectos de protección de las fibras musculares a nivel del tejido. Una alta dosis de coenzima Q10 demostró ser más efectiva en la reducción de la inflamación; adicionalmente, el tratamiento combinado de Resveratrol y coenzima Q10 proporcionó efectos protectores de membrana, además de los efectos anti-inflamatorios del Resveratrol cuyo nivel no alcanzó la efectividad suficiente al ser administrado en forma exclusiva.

[Biological properties of coenzyme Q10 and its effects on immunity]. / Biologické vlastnosti koenzýmu Q10 a jeho vplyv na imunitu.

Coenzyme Q10, a vitamin-like substance, represents a components of the complex antioxidant system of the human organism. The paper presents its structure, physiological function and the role in the disease pathogenesis with the accent on the supplementation therapy during human immune system disturbances, including infectious and oncological diseases.

Coenzyme Q10 in vesicles composed of archaeal ether lipids or conventional lipids enhances the immuno-adjuvanticity to encapsulated protein.

Cellular accumulation, tissue distribution, and immuno-adjuvanticity were evaluated for liposomal CoQ10 prepared from either distearoylphosphatidylcholine:dicetylphosphate:cholesterol (4:1:5, mol. ratio) (conventional liposomes) or from the total polar lipids of the archaeon Methanosarcina mazei (archaeosomes). Liposomal CoQ10 vesicles of approximately 100 nm diameter, containing up to 179 mumol of CoQ10 per mg of lipid have been evaluated using J774A.1 macrophages and Balb/c mice. Archaeosomes uptake by J774A.1 macrophages was better than with the conventional liposome, and the incorporation of CoQ10 enhanced the uptake of both lipid vesicle types. All vesicle types were detected in the liver and spleen of mice (4-27% of injected dose) within 3 h of intraperitoneal injection. Moreover, incorporation of CoQ10 into lipid vesicles enhanced the immuno-adjuvanticity of both conventional liposomes and archaeosomes, to achieve approximately a doubling in the titres of BSA-specific antibody in sera to 169 and 430 micrograms ml-1, respectively. Increases in IgG1 and IgG2a/2b accounted for most of the CoQ10-induced increases in anti-BSA titres. These results are rationalized on the basis of surface hydrophobicity and opsonization changes induced by the presence of CoQ10 in vesicles. We suggest that liposomal CoQ10 has potential as a new generation of vaccine delivery system to enhance the immune response. Its use as a novel delivery system may be particularly effective under pathological conditions where the occurrence of an oxidative stress condition significantly impairs the immune system functions.

Immunostimulation. Clinical and experimental perspectives.

Three classes of immunostimulating drugs are described, each representing a different approach to the problem of pharmacological immunostimulation. The rationale for the use of microbes or microbial agents as immunostimulators rests on the fact that some micro-organisms, especially those that replicate intracellularly, carry a special potential to activate macrophages. Clinically, the use of these agents in patients with tumors and infections has been disappointing; however, there have been positive exceptions like the responsiveness of melanomas and bladder carcinomas to the injection of BCG. Many of the inconclusive results may be due to insecurities in the dosage of microbial preparations and to a general lack in standardization. Some structures with high efficacy and low toxicity which have recently evolved from this field deserve further investigation. A number of structurally unrelated synthetic compounds was found to influence immune parameters. Levamisole can today be classified as an immunostimulating drug with limited utility in recurring infections and in chronic polyarthritis. Several immunostimulating drugs which have attracted interest contain a purine as the effective component. This is not surprising in view of the fact that many genetically determined immunodeficiencies can be traced to defects of enzymes which play a crucial role in purine biosynthesis. Finally, the potential role of lymphokines as stimulators of the immunosystem is briefly described. Some of these glycoproteins have recently become available for clinical trials. Others will be made available through genetic engineering. The therapeutic utility of these compounds is not yet clear; they will, however, be of great value as probes for the study of immune functions and for the development of immunopharmacology.

Immunological studies on beef-heart ubiquinol--cytochrome c reductase (complex III)

Antibodies against isolated beef-heart ubiquinol--cytochrome c reductase (complex III) have been characterized. Antibodies to complex III react strongly with isolated beef heart complex III and intact beef heart mitochondria, as shown by immunodiffusion and rocket electrophoresis experiments. The complex III content of intact mitochondria can be quantitated with rocket electrophoresis using isolated complex III as a standard. Antibodies to complex III also react with beef liver mitochondria and with both heart and liver mitochondria from rats. The latter are very weak antigens compared to beef heart material. Antibodies to complex III do not react with respiratory chain complexes I and IV, or F1-ATPase from beef heart mitochondria, but gives a slight, but variable, reaction with complex II and the membrane fraction isolated from complex V (oligomycin-sensitive ATPase). Antigenic sites are located on at least five of the seven peptides of complex III. These peptides are presumably lacking in respiratory chain complexes which do not react with antibodies to complex III, and are assumed to be uniquely located in complex III. Antiserum against complex III inhibitis duroquinol--cytochrome c reductase activity in isolated complex III and in complex III incorporated into phospholipid vesicles. Oxidation of NADH and succinate is not affected in submitochondrial particles treated with 6-times more antibody than required for complete inhibition of enzyme activity in free complex III or in complex III-phospholipid vesicles.

Immunostimulation or immunodepression?

Our experimental studies and extensive literature survey established that the overall response of an experimentally modified host defense system is strongly dose-dependent, irrespective of either the modifying agent or the test model system. If a sufficiently broad dose range is used, an irregular, nonlinear, nonmonotonic response curve is formed, generally W- or M-shaped, depending on the parameters selected for the representation, with two peaks of relative maximal effect. Accordingly, a modifying agent may exhibit, in some cases, dual effect--stimulation and depression, each at different dose levels. This typical response is defined as characteristic of the entire host defense system and therefore implies a biologically integrated system. The described dose-response relationship mandates the use of multiple doses in evaluation experiments, to establish efficacy and especially to design optimal dose schedules for experimental and clinical application of any agent modifying the host defense system activity.