This thesis describes the development of separate assays to measure coenzyme Q₁₀ (CoQ₁₀) and vitamin K. Coenzyme Q is essential for the mitochondrial electron transport chain, and vitamin K for the blood coagulation cascade. Vitamin K deficiency is associated with haemorrhagic disease of the new-born, and CoQ₁₀ deficiency with HMG-CoA-reductase inhibitor (statin) therapy and heart failure. Coenzyme Q and vitamin K are usually measured by HPLC, using electrochemical and ultraviolet, and electrochemical and fluorescence detection, respectively. For vitamin K1, the limit of detection achieved using fluorescence and electrochemical detection was 0.28 and 0.12 nmol/L, respectively. Sensitivity of fluorescence detection is improved by using protic solvents in the mobile phase, and platinum-black catalysed alcohol reduction. The lipophilicity and low endogenous concentrations of vitamin K1 hinder its measurement, and further work is required to produce a rapid, reliable and robust assay for its measurement in human plasma. The limits of detection achieved using fluorescence, ultraviolet and electrochemical detection to measure CoQ₁₀ were 29, 4.8, and 0.34 nmol/L, respectively. Plasma CoQ₁₀ is not stable during long term storage at -13 ℃, but at -80 ℃ it is stable for at least 18 months. The reference interval for plasma total CoQ₁₀ in the New Zealand population is 0.47 - 1.80 µmol/L. There is no clinical requirement for stratification of the reference interval according to gender. Coenzyme Q₁₀ in human plasma is homeostatically controlled, varying little over a two month interval in healthy young males. Coenzyme Q₁₀ supplements have significantly different bioavailability, with the median increase in plasma CoQ₁₀ ranging from 0.14 to 0.59 µmol/L for seven different supplement brands. There is a large inter-individual variation in CoQ₁₀ absorption, and hence plasma concentrations should be monitored during supplementation. A plateau in CoQ₁₀ absorption, from a single dose, at approximately 200 mg suggests that the maximum dose ingested at one time should be 200 mg or less. Q-Gel capsules containing 30 mg of CoQ₁₀ are twice as effective at raising blood CoQ₁₀ as 100 mg capsules. Plasma CoQ₁₀ in patients with chronic heart failure are significantly lowered by approximately 33% when these patients receive Atorvastatin for six weeks. The absolute decrease in CoQ₁₀ showed a significant correlation with worsening endothelial function (r = + 0.548, p = 0.011). Coenzyme Q₉ was shown to be present in human plasma with a reference interval of 8.8 - 47.0 nmol/L.

This thesis describes the development of separate assays to measure coenzyme Q₁₀ (CoQ₁₀) and vitamin K. Coenzyme Q is essential for the mitochondrial electron transport chain, and vitamin K for the blood coagulation cascade. Vitamin K deficiency is associated with haemorrhagic disease of the new-born, and CoQ₁₀ deficiency with HMG-CoA-reductase inhibitor (statin) therapy and heart failure. Coenzyme Q and vitamin K are usually measured by HPLC, using electrochemical and ultraviolet, and electrochemical and fluorescence detection, respectively. For vitamin K1, the limit of detection achieved using fluorescence and electrochemical detection was 0.28 and 0.12 nmol/L, respectively. Sensitivity of fluorescence detection is improved by using protic solvents in the mobile phase, and platinum-black catalysed alcohol reduction. The lipophilicity and low endogenous concentrations of vitamin K1 hinder its measurement, and further work is required to produce a rapid, reliable and robust assay for its measurement in human plasma. The limits of detection achieved using fluorescence, ultraviolet and electrochemical detection to measure CoQ₁₀ were 29, 4.8, and 0.34 nmol/L, respectively. Plasma CoQ₁₀ is not stable during long term storage at -13 ℃, but at -80 ℃ it is stable for at least 18 months. The reference interval for plasma total CoQ₁₀ in the New Zealand population is 0.47 - 1.80 µmol/L. There is no clinical requirement for stratification of the reference interval according to gender. Coenzyme Q₁₀ in human plasma is homeostatically controlled, varying little over a two month interval in healthy young males. Coenzyme Q₁₀ supplements have significantly different bioavailability, with the median increase in plasma CoQ₁₀ ranging from 0.14 to 0.59 µmol/L for seven different supplement brands. There is a large inter-individual variation in CoQ₁₀ absorption, and hence plasma concentrations should be monitored during supplementation. A plateau in CoQ₁₀ absorption, from a single dose, at approximately 200 mg suggests that the maximum dose ingested at one time should be 200 mg or less. Q-Gel capsules containing 30 mg of CoQ₁₀ are twice as effective at raising blood CoQ₁₀ as 100 mg capsules. Plasma CoQ₁₀ in patients with chronic heart failure are significantly lowered by approximately 33% when these patients receive Atorvastatin for six weeks. The absolute decrease in CoQ₁₀ showed a significant correlation with worsening endothelial function (r = + 0.548, p = 0.011). Coenzyme Q₉ was shown to be present in human plasma with a reference interval of 8.8 - 47.0 nmol/L.

Coenzyme Q10 is a lipid-soluble coenzyme, synthesized in mammalian tissue to support energy production, and also act as an antioxidant. Certain medication, stress and age may deplete the body’s endogenous Coenzyme Q10 store. Numerous disease conditions have been shown to benefit from Coenzyme Q10 supplementation. It is a lipid-soluble component of virtually all cell membranes, and is located in the hydrophobic domain of the phospholipid bilayer of cellular membranes. It is also the only known lipid-soluble antioxidant that animal cells can synthesize de novo, and for which there exist enzymatic mechanisms which can regenerate it from its oxidized product formed in the course of its antioxidant function. The aim of this study was to investigate the cellular effects of Coenzyme Q10 and Triton X-100 on primary chicken embryo heart and muscle cell cultures. Triton X-100, a well known membrane disrupter, extensively used by cell biologists for that purpose, was used to investigate whether Coenzyme Q10 might offer protection to cell membranes exposed to disruption. Due to the correlation found between the chemical structures of nonylphenol and Triton X-100, it was decided to determine whether Triton X-100 possess estrogenic properties. Using the Recombinant Yeast Screen Assay for estrogenic activity, it was found that Triton X-100 induced weak estrogenic activity. The primary heart and skeletal muscle cell cultures were established by harvesting skeletal muscle tissue and hearts from 13 day old chicken embryos. After establishment of the cell cultures, the concentrations of Coenzyme Q10 and Triton X-100 were tested for cytotoxicity using the MTT, NR, and CV assays, in the form of a combined colorimetric cytotoxicity assay. The MTT assay revealed an increase in cell viability in both cell cultures upon exposure to Triton X-100 and Coenzyme Q10, alone, and in combination. Triton X-100 and Coenzyme Q10, alone, and in combination, caused a decrease in lysosomal membrane integrity, as measured by the NR assay, and both substances, alone, and in combination, had no effect on cellular proteins, as measured by the CV assay. Scanning electron microscopy (SEM) was done to determine the cellular effect of heart and skeletal muscle cell cultures on the external surface, more specifically the membranes, of cells in culture. Triton X-100 in the concentrations used in the study, caused membrane disruption, ranging from complete membrane lyses at the highest concentrations to membrane ruptures and apoptotic blebbing in lower concentrations. SEM revealed that no adverse effects were caused by Coenzyme Q10 on the membrane structure, in dissimilarity, cell differentiation and proliferation, including myoblast formation were seen in the presence of all the concentrations of Coenzyme Q10. Numerous ion channels were observed on cellular surfaces exposed to Coenzyme Q10. Upon exposure to 0.005% Triton X-100, after pre-treatment with Coenzyme Q10, SEM revealed a “membrane patch” formation on membranes disrupted by Triton X-100. Damage to cell membranes in the presence of Triton X-100, were less severe when cells were pre-treated with Coenzyme Q10. Confocal microscopy was utilized to investigate intracellular occurrences in the presence of Triton X-100 and Coenzyme Q10. Using Mito Tracker Red to stain active respiring mitochondria and DAPI to stain nuclei, confocal microscopy confirmed the observations made by SEM, that Coenzyme Q10 enhance cell proliferation and differentiation, and that the adverse effects to cells exposed to Triton X-100 are less severe after pre-treatment with Coenzyme Q10. ROS generation was detected, using dichlorodihydrofluorescein diacetate, in cultures exposed to Triton X-100, and none in the presence of Coenzyme Q10. In the presence of Triton X-100, after pre-treatment with Coenzyme Q10, ROS generation was remarkably lower. The study provided apparent evidence that Coenzyme Q10 offer protection to cardiac and skeletal muscle cells in culture after exposure to relatively low concentrations of the membrane disrupter Triton X-100. Coenzyme Q10 also promotes the process of proliferation and differentiation in primary chicken embryonic cultures of heart and skeletal muscle cells. / Dissertation (MSc)--University of Pretoria, 2008. / Anatomy / unrestricted

Les bienfaits des acides gras oméga-3, essentiellement l’EPA (C20:5n-3) et le DHA (C22:6n-3) sont bien élucidés dans la littérature. Ils jouent en effet, un rôle essentiel dans la prévention de nombreuses maladies neurodégénératives et cardiovasculaires. Ces acides gras polyinsaturés à longue chaîne sont majoritairement retrouvés dans des sources d’origines marines. Dans ce contexte, nous nous sommes intéressés d’une part à l’effet du complexe phospholipopeptidique provenant de l’hydrolyse enzymatique des têtes de saumon, sur l’anxiété et le stress oxydant dans le cadre d’une étude comportementale effectuée sur un modèle murin. D’autre part, nous avons mis en place une approche de double vectorisation, sous formes de nanoémulsions, visant à augmenter la biodisponibilité de deux molécules hydrophobes et bioactives (coenzyme Q10 et curcumine) en utilisant les lipides totaux (phospholipides et triacylglycérols) du complexe phospholipopeptidique riche en EPA et en DHA. Les résultats de ce travail ont montré que le CPLP, sa fraction lipidique et peptidique ont un effet anxiolytique à une dose de 600 mg de CPLP/jour pendant 14 jours de traitement. Il a également été démontré dans cette étude que l’hydrolysat peptidique du CPLP diminue significativement, à double dose, le stress oxydant en baissant le niveau endogène des espèces réactives de l’oxygène (ROS) dans les neurones. D’autre part, pour une utilisation thérapeutique, la biodisponibilité du CoQ10 vectorisé à forte dose est améliorée jusqu’à 38 fois par la formulation huileuse composée de lipides polaires du CPLP. Concernant la supplémentation classique en CoQ10 en tant que complément alimentaire, la formulation émulsionnée présente une meilleure disponibilité à dose aigüe, avec une concentration plasmatique deux fois plus élevée que la formulation de référence. Malgré une activité anticancéreuse reconnue pour la curcumine, sa faible solubilité diminue sa biodisponibilité et limite de ce fait son utilisation. La formulation nanoémulsionnée de curcumine contribue à inhiber la prolifération de cellules cancéreuses (MCF7) / The benefits of omega 3 fatty acids, mainly EPA (C20:5n-3) and DHA (C22:6n-3) are well understood in the literature. They indeed play an essential role in the prevention of many neurodegenerative and cardiovascular diseases. These polyunsaturated fatty acids are mostly found in marine sources. In this context, we were interested on the effects of phospholipopeptidic complex from the enzymatic hydrolysis of salmon heads on anxiety and oxidative stress using a behavioural study (mouse model). On the other hand, we have developed a double vectorization operating nanoemulsions, to increase the bioavailability of two hydrophobic and bioactive molecules (conenzyme Q10 and curcumine) by total lipids (phospholipids and triacylglycerols) from the phospholipopeptidic complex rich in EPA and DHA. The results of this study showed that the CPLP, its lipid and peptide fractions have an anxiolytic effect at a dose of 600 mg of CPLP / day for 14 days of treatment. It was also demonstrated that the peptide’s hydrolyzate ingested at double dose decreases significantly the oxidative stress by lowering the endogenous level of reactive oxygen species (ROS) in neurons. For therapeutic uses, the bioavailability of CoQ10 increased up to 38 times compared to referential formulation when verctorized at high dose in the oily formulation composed of CPLP’s total lipids. Regarding conventional CoQ10 supplementation as a dietary supplement, the emulsified formulation has a better availability at single dose, with plasma concentrations two times higher than the reference formulation. Although the anti-cancer activity of curcumine is highlighted, its low solubility and hence its low bioavailability, are factors limiting its use. The formulation of nanoemulsified curcumine allows a significant reduction in the proliferation of cancer cells (MCF7)

A coenzima Q10 é uma provitamina lipossolúvel sintetizada endogenamente e naturalmente encontrada em alimentos como a carne vermelha, peixes, cereais, brócolis e espinafre. É comercializada como suplemento alimentar e utilizada em formulações cosméticas. Localiza-se na membrana de organelas celulares como retículo endoplasmático, vesículas e membrana interna da mitocôndria, onde atua como um cofator essencial na cadeia respiratória. Apresenta propriedades antioxidantes e potencial no tratamento de doenças neurodegenerativas e neuromusculares. O objetivo deste trabalho foi investigar os possíveis efeitos protetores de uma formulação hidrossolúvel de coenzima Q10 em células PC12 expostas à cisplatina, um fármaco antineoplásico que tem a neurotoxicidade como um dos fatores limitantes à sua utilização. A linhagem celular PC12 (feocromocitoma de ratos) utilizada nesta investigação é um reconhecido modelo in vitro para estudos neuronais. Os métodos empregados foram os ensaios do MTT, cometa, citoma micronúcleo com bloqueio da citocinese, crescimento de neuritos e análise da expressão do gene Tp53. Os resultados obtidos na avaliação da citotoxicidade da coenzima Q10 (0,1 - 20 µg/mL) mostraram que este antioxidante foi citotóxico às células PC12 na concentração de 20,0 µg/mL e não apresentou citotoxicidade em baixas concentrações. Para os ensaios do citoma e cometa, foram selecionadas três concentrações não citotóxicas de coenzima Q10 (0,1; 0,5 e 1,0 µg/mL) que não apresentaram mutagenicidade e genotoxicidade às células PC12. O efeito protetor da coenzima Q10 sobre a cisplatina no ensaio do citoma foi caracterizado pela diminuição da freqüência de micronúcleos e brotos nucleares, entretanto a proteção da coenzima Q10 não foi evidenciada no ensaio cometa. Alterações significativas na expressão do gene Tp53 não foram observadas no tratamento coenzima Q10 (1,0 µg/mL) associado à cisplatina (0,1 µg/mL). A coenzima Q10 (0,1 e 1,0 µg/mL) não foi neurotóxica em células PC12 indiferenciadas e diferenciadas após exposição ao fator de crescimento do nervo, e seu melhor efeito neuroprotetor foi observado na menor concentração avaliada. A coenzima Q10 reduziu a citotoxicidade da cisplatina (10,0 µg/mL) em células PC12 indiferenciadas e estimulou o crescimento de neuritos em células PC12 diferenciadas. A determinação dos efeitos citoprotetores da coenzima Q10 em um modelo neuronal é importante para elucidar possíveis estratégias de neuroproteção que poderiam ser aplicadas aos pacientes submetidos à quimioterapia. / Coenzyme Q10 is a liposoluble provitamin endogenously synthesized and naturally found in various foods items, such as meat, fish, cereals, broccoli and spinach. It is a dietary supplement in some countries and used in cosmetic formulations. Coenzyme Q10 is located in the membrane of cellular organelles such as endoplasmic reticulum, vesicles and inner mitochondrial membrane, where acts as an essential cofactor in the respiratory chain. It has antioxidant properties and potential in the treatment of neurodegenerative and neuromuscular diseases. The objective of this study was to investigate the possible protective effects of a water-soluble formulation of coenzyme Q10 in PC12 cells exposed to cisplatin, an anticancer drug that has neurotoxicity as a dose-limiting factor. The PC12 cell line (rat pheocromocytoma) used in this investigation is a recognized in vitro model for neuronal studies. The methods used were the MTT, comet, cytokinesis-block micronucleus cytome, neurite outgrowth assays and expression of Tp53 gene. The results obtained in the cytotoxicity of coenzyme Q10 (0.1-20 µg/mL) showed that this antioxidant was cytotoxic to PC12 cell at a concentration of 20.0 µg/mL and it was not cytotoxic at low concentrations. For the cytome and comet assays, were selected three non-cytotoxic concentrations of coenzyme Q10 (0.1, 0.5 and 1.0 µg/mL) without mutagenicity and genotoxicity PC12 cells. The protective effect of coenzyme Q10 in cytome assay was characterized by decreased frequency of micronuclei and nuclear buds induced by cisplatin, however the protection of coenzyme Q10 was not evidenced by the comet assay. No significant change in the Tp53 gene expression were observed in the coenzyme Q10 (1.0 µg/mL) plus cisplatin (0.1 µg/mL) treatment. Coenzyme Q10 (0.1 and 1.0 µg/mL) was not neurotoxic in undifferentiated and nerve growth factor differentiated PC12 cells and the lowest concentration evaluated showed the best neuroprotective effect. The coenzyme Q10 treatment reduced the citotoxicity of cisplatin (10.0 µg/mL) in undifferentiated PC12 cells and stimulated the neurite outgrowth in differentiated PC12 cells. Determination of the cytoprotective effects of the coenzyme Q10 in a neuronal model is important to elucidate possible strategies for neuroprotection that could be applied to patients undergoing chemotherapy.

Dysfunction of Mitochondrial Respiratory Chain in Rostral Ventrolateral Medulla During Experimental Endotoxemia Sepsis is a complex pathophysiologic state resulting from an exaggerated whole-body inflammatory response to infection or injury. Metabolic disturbances, abnormal regulation of blood flow and diminished utilization of oxygen at the cellular level may account for tissue damage and lead to multiple organ failure and death. As the primary site of cellular energy generation is the mitochondrion, it presents itself as an important target for the septic cascade. In this regard, the notion that bioenergetic failure due to mitochondrial dysfunction contributes to organ failure during sepsis has received attention. We established the low frequency fluctuations in the systemic arterial pressure signals are related to the sympathetic neurogenic vasomotor tone, and reflect the functional integrity of the brain stem. Their origin is subsequently traced to the premotor sympathetic neurons at the rostral ventrolateral medulla (RVLM), whose neuronal activity is intimately related to the ¡§life-and-death¡¨ process. Based on a rat model of experimental endotoxemia that provides continuous information on changes in neuronal activity in the RVLM, the present study was undertaken to evaluate whether changes in mitochondrial respiratory functions are associated with death arising from sepsis. We also evaluated the efficacy of a new water-soluble coenzyme Q10 (CoQ10, ubiquinone) formula in the protection against fatality during endotoxemia by microinjection into bilateral RVLM. Dysfunction of Mitochondrial Respiratory Chain in Rostral Ventrolateral Medulla During Experimental Endotoxemia in the Rat We investigated the functional changes in mitochondrial respiratory chain at the RVLM in an experimental model of endotoxemia that mimics systemic inflammatory response syndrome. Experiments were carried out in adult male Sprague-Dawley rats that were maintained under propofol anesthesia. Intravenous administration of E. coli lipopolysaccharide (LPS; 30 mg/kg) induced progressive hypotension, with death ensued within 4 hours. The sequence of cardiovascular events during this LPS-induced endotoxemia can be divided into a reduction (Phase I), followed by an augmentation (Phase II; ¡§pro-life¡¨ phase) and a secondary decrease (Phase III; ¡§pro-death¡¨ phase) in the power density of the vasomotor components (0-0.8 Hz) of systemic arterial pressure (SAP) signals. Enzyme assay revealed significant decrease of the activity of NADH cytochrome c reductase (Complex I+III) and cytochrome c oxidase (Complex IV) in the RVLM during all 3 phases of endotoxemia. On the other hand, the activity of succinate cytochrome c reductase (Complex II+III) remained unaltered. Neuroprotective Effects of Coenzyme Q10 at Rostral ventrolateral Medulla Against Fatality During Experimental Endotoxemia in the Rat CoQ10 is a highly mobile electron carrier in the mitochondrial respiratory chain that also acts as an antioxidant. We evaluated the neuroprotective efficacy of CoQ10 against fatality in an experimental model of endotoxemia, using a novel water-soluble formulation of this quinone derivative. In Sprague-Dawley rats maintained under propofol anesthesia, intravenous administration of E. coli LPS (30 mg/kg) induced experimental endotoxemia. Pretreatment by microinjection bilaterally of CoQ10 (1 or 2 mg) into RVLM significantly diminished mortality, prolonged survival time, and reduced the slope or magnitude of the LPS-induced hypotension. CoQ10 pretreatment also significantly prolonged the duration of Phase II endotoxemia and augmented the total power density of the vasomotor components of SAP signals in Phase II endotoxemia. The increase in superoxide anion production induced by LPS at the RVLM during Phases II and III endotoxemia was also significantly blunted. Conclusion The present study revealed that selective dysfunction of respiratory enzyme Complexes I and IV in the mitochondrial respiratory chain at the RVLM is closely associated with fatal endotoxemia. CoQ10 provides neuroprotection against fatality during endotoxemia by acting on the RVLM. We further found that a reduction in superoxide anion produced during endotoxemia at the RVLM may be one of the mechanisms that underlie the elicited neuroprotection of CoQ10. These findings therefore open a new direction for future development of therapeutic strategy in this critical, complicated and highly fatal condition known as sepsis.

Thesis (MNutrition (ITE))--Stellenbosch University, 2012. / ENGLISH ABSTRACT: Background Statins are drugs of known efficacy in the treatment of hypercholesterolaemia. However, statin-induced myopathy, an adverse effect of statins in up to 15% of its users, has warranted a reduction in the prescription dose or discontinuation of the drug. The exact mechanism of statin-induced myopathy is unknown, but the potential of Coenzyme Q10 (CoQ10) as treatment has been recognized due to decreased human plasma CoQ10 levels found after statin use and the concomitant role of CoQ10 in muscle function. Objectives This systematic review assessed the effect of CoQ10 supplementation on: the severity of statin-induced myopathic symptoms, levels of plasma creatine kinase, intramuscular and plasma CoQ10, as well as whether any adverse effects of CoQ10 supplementation such as abdominal pain, nausea and vomiting or headaches were experienced. Search methods Two searches for studies were conducted in The Cochrane Central Register of Controlled Trials (inception to March 2011 and inception to November 2011), MEDLINE (inception to March 2011 and inception to November 2011), Web of Science (inception to March 2011 and inception to November 2011), Science Direct (inception to March 2011 and inception to February 2012), Wiley Online Library (inception to March 2011 and inception to February 2012), Springerlink (inception to April 2011 and inception to February 2012), EBSCOhost [Academic Search Premier and CAB abstracts (inception to March 2011 and inception to February 2012), CINAHL (inception to March 2011 and inception to November 2011)], Scopus (inception to March 2011 and inception to November 2011) and Google Scholar (inception to March 2011 and inception to February 2012). Reference lists of articles were hand searched for relevant clinical trials. Only trials with a full text were included in the review. Selection criteria Randomised controlled trials (RCTs) were included with adult participants (mean of 18-64.99 years) of all race/ethnic groups and gender on statin therapy with reported myopathic symptoms from an unknown cause. The intervention was in the form of a pure oral supplement of CoQ10 irrespective of dose, duration and frequency, and the control in the form of a placebo, a similar antioxidant, or no intervention. Outcomes included the severity of myopathic symptoms, levels of plasma creatine kinase (U/L), intramuscular CoQ10 (μmol/kg) and plasma CoQ10 (μmol/L), as well as adverse effects of CoQ10. Data collection and analysis The principle investigator and one independent reviewer selected the studies, extracted data and assessed for risk of bias using the Cochrane Collaboration‘s tool for assessing risk of bias. Authors of relevant clinical trials were contacted for additional information. Results Two RCTs were included in the review, totaling 76 participants. A meta-analysis could not be performed, thus the review is narrative. There were an insufficient number of RCTs to confirm whether routine supplementation of CoQ10 improves statin-induced myopathic symptoms. Conclusions More and larger RCTs are required to determine the efficacy of CoQ10 supplementation in statin-induced myopathy. Consensus needs to be reached regarding the definition and measurement instrument/s of myopathy so that results of future studies can easily be compared and synthesized. / AFRIKAANSE OPSOMMING: Agtergrond Statiene is medikasie bekend vir die effektiewe behandeling van hipercholesterolemie. Statien-geïnduseerde miopatie is egter 'n newe-effek wat voorkom in tot 15% van gebruikers, wat 'n vermindering in die voorgeskrewe dosis of staking van die medikasie tot gevolg het. Die presiese meganisme van statien-geïnduseerde miopatie is onbekend, maar die potensiaal van Koënsiem Q10 (CoQ10) is geïdentifiseer as 'n moontlike behandeling aangesien menslike plasma CoQ10 vlakke verlaag na die gebruik van statiene en as gevolg van die rol van CoQ10 in spierfunksie. Doelwitte Hierdie sistematiese literatuuroorsig het die effek van CoQ10 supplementasie bepaal op: die graad van statien-geïnduseerde miopatiese simptome, plasma kreatien kinase vlakke, intra-muskulêre en plasma CoQ10 vlakke, asook die teenwoordigheid van enige newe-effekte van CoQ10 supplementasie soos abdominale pyn, naarheid en braking of hoofpyne. Soektogstrategie Twee soektogte vir studies is uitgevoer in The Cochrane Central Register of Controlled Trials (ontstaan tot Maart 2011 en ontstaan tot November 2011), MEDLINE (ontstaan tot Maart 2011 en ontstaan tot November 2011), Web of Science (ontstaan tot Maart 2011 en ontstaan tot November 2011), Science Direct (ontstaan tot Maart 2011 en ontstaan tot Februarie 2012), Wiley Online Library (ontstaan tot Maart 2011 en ontstaan tot Februarie 2012), Springerlink (ontstaan tot April 2011 en ontstaan tot Februarie 2012), EBSCOhost [Academic Search Premier en CAB abstracts (ontstaan tot Maart 2011 en ontstaan tot Februarie 2012), CINAHL (ontstaan tot Maart 2011 en ontstaan tot November 2011)], Scopus (ontstaan tot Maart 2011 en ontstaan tot November 2011) en Google Scholar (ontstaan tot Maart 2011 en ontstaan tot Februarie 2012). Verwysingslyste van artikels is ook met die hand nagegaan vir relevante kliniese proewe. Slegs kliniese proewe waarvan die volteks beskikbaar was, is ingesluit in die oorsig. Seleksiekriteria Ewekansige gekontroleerde proewe (EGP) is ingesluit met volwasse deelnemers (gemiddeld 18-64.99 jaar) van alle rasse/etniese groepe en geslag op statien-terapie met gerapporteerde miopatie simptome van onbekende oorsaak. Die intervensie was 'n suiwer orale supplement van CoQ10 ongeag die dosis, duurte en frekwensie, en die kontrole 'n plasebo, soortgelyke antioksidant, of geen intervensie. Uitkomste het ingesluit: die graad van miopatie simptome, vlakke van plasma kreatien kinase (U/L), intra-muskulêre CoQ10 (μmol/kg) en plasma CoQ10 (μmol/L), sowel as newe-effekte van CoQ10. Dataversameling en -analise Die hoof ondersoeker en een onafhanklike hersiener het die seleksie van studies en data-ekstraksie onderneem en die risiko vir sydigheid geassesseer deur gebruik te maak van die Cochrane Collaboration’s tool for assessing risk of bias. Outeurs van relevante kliniese proewe is geraadpleeg vir addisionele inligting Resultate Twee EGP is ingesluit in die oorsig met 'n totaal van 76 deelnemers. 'n Meta-analise kon nie uitgevoer word nie, dus is die oorsig beskrywend. Daar was te min EGP om te bewys dat roetine supplementasie van CoQ10 statien-geïnduseerde miopatiese simptome verbeter. Gevolgtrekkings Meer en groter EGP is nodig om die effektiwiteit van CoQ10 supplementasie in statien-geïnduseerde miopatie te bepaal. Konsensus moet bereik word ten opsigte van die definisie en metingsinstrument/e van miopatie sodat die resultate van toekomstige studies makliker vergelyk en verwerk kan word.

A coenzima Q10 é uma provitamina lipossolúvel sintetizada endogenamente e naturalmente encontrada em alimentos como a carne vermelha, peixes, cereais, brócolis e espinafre. É comercializada como suplemento alimentar e utilizada em formulações cosméticas. Localiza-se na membrana de organelas celulares como retículo endoplasmático, vesículas e membrana interna da mitocôndria, onde atua como um cofator essencial na cadeia respiratória. Apresenta propriedades antioxidantes e potencial no tratamento de doenças neurodegenerativas e neuromusculares. O objetivo deste trabalho foi investigar os possíveis efeitos protetores de uma formulação hidrossolúvel de coenzima Q10 em células PC12 expostas à cisplatina, um fármaco antineoplásico que tem a neurotoxicidade como um dos fatores limitantes à sua utilização. A linhagem celular PC12 (feocromocitoma de ratos) utilizada nesta investigação é um reconhecido modelo in vitro para estudos neuronais. Os métodos empregados foram os ensaios do MTT, cometa, citoma micronúcleo com bloqueio da citocinese, crescimento de neuritos e análise da expressão do gene Tp53. Os resultados obtidos na avaliação da citotoxicidade da coenzima Q10 (0,1 - 20 µg/mL) mostraram que este antioxidante foi citotóxico às células PC12 na concentração de 20,0 µg/mL e não apresentou citotoxicidade em baixas concentrações. Para os ensaios do citoma e cometa, foram selecionadas três concentrações não citotóxicas de coenzima Q10 (0,1; 0,5 e 1,0 µg/mL) que não apresentaram mutagenicidade e genotoxicidade às células PC12. O efeito protetor da coenzima Q10 sobre a cisplatina no ensaio do citoma foi caracterizado pela diminuição da freqüência de micronúcleos e brotos nucleares, entretanto a proteção da coenzima Q10 não foi evidenciada no ensaio cometa. Alterações significativas na expressão do gene Tp53 não foram observadas no tratamento coenzima Q10 (1,0 µg/mL) associado à cisplatina (0,1 µg/mL). A coenzima Q10 (0,1 e 1,0 µg/mL) não foi neurotóxica em células PC12 indiferenciadas e diferenciadas após exposição ao fator de crescimento do nervo, e seu melhor efeito neuroprotetor foi observado na menor concentração avaliada. A coenzima Q10 reduziu a citotoxicidade da cisplatina (10,0 µg/mL) em células PC12 indiferenciadas e estimulou o crescimento de neuritos em células PC12 diferenciadas. A determinação dos efeitos citoprotetores da coenzima Q10 em um modelo neuronal é importante para elucidar possíveis estratégias de neuroproteção que poderiam ser aplicadas aos pacientes submetidos à quimioterapia. / Coenzyme Q10 is a liposoluble provitamin endogenously synthesized and naturally found in various foods items, such as meat, fish, cereals, broccoli and spinach. It is a dietary supplement in some countries and used in cosmetic formulations. Coenzyme Q10 is located in the membrane of cellular organelles such as endoplasmic reticulum, vesicles and inner mitochondrial membrane, where acts as an essential cofactor in the respiratory chain. It has antioxidant properties and potential in the treatment of neurodegenerative and neuromuscular diseases. The objective of this study was to investigate the possible protective effects of a water-soluble formulation of coenzyme Q10 in PC12 cells exposed to cisplatin, an anticancer drug that has neurotoxicity as a dose-limiting factor. The PC12 cell line (rat pheocromocytoma) used in this investigation is a recognized in vitro model for neuronal studies. The methods used were the MTT, comet, cytokinesis-block micronucleus cytome, neurite outgrowth assays and expression of Tp53 gene. The results obtained in the cytotoxicity of coenzyme Q10 (0.1-20 µg/mL) showed that this antioxidant was cytotoxic to PC12 cell at a concentration of 20.0 µg/mL and it was not cytotoxic at low concentrations. For the cytome and comet assays, were selected three non-cytotoxic concentrations of coenzyme Q10 (0.1, 0.5 and 1.0 µg/mL) without mutagenicity and genotoxicity PC12 cells. The protective effect of coenzyme Q10 in cytome assay was characterized by decreased frequency of micronuclei and nuclear buds induced by cisplatin, however the protection of coenzyme Q10 was not evidenced by the comet assay. No significant change in the Tp53 gene expression were observed in the coenzyme Q10 (1.0 µg/mL) plus cisplatin (0.1 µg/mL) treatment. Coenzyme Q10 (0.1 and 1.0 µg/mL) was not neurotoxic in undifferentiated and nerve growth factor differentiated PC12 cells and the lowest concentration evaluated showed the best neuroprotective effect. The coenzyme Q10 treatment reduced the citotoxicity of cisplatin (10.0 µg/mL) in undifferentiated PC12 cells and stimulated the neurite outgrowth in differentiated PC12 cells. Determination of the cytoprotective effects of the coenzyme Q10 in a neuronal model is important to elucidate possible strategies for neuroprotection that could be applied to patients undergoing chemotherapy.

Introduction: Coenzyme Q10 (CoQ10) is a fat-soluble substance (ubiquinone) which has a bright orange color in appearance and is widely distributed (ubiquitous) in animals and many bacteria. CoQ10’s presence is most prevalent in mitochondria and it is involved in aerobic cellular respiration and aides in converting ingested nutrients into a readily accessible form of energy, specifically ATP (adenosine triphosphate). CoQ10 is supplied through our diets and can be found more in dark leafy green vegetables, fish and organ meats. CoQ10 supplementation should be beneficial due to its characteristic antioxidant scavenging of free radicals that our body produces while in the cellular respiration process for generating energy from nutrients. Although CoQ10 has great antioxidant benefit, a challenge remains for supplement manufacturers to deliver a sufficient does of this sparingly soluble molecule. Dietary supplements do not have the significant FDA oversight that exists for legend drugs, resulting in significant variability within and between brands. The main hypothesis of this project is that commercially available CoQ10 supplements don’t deliver a sufficient mass of CoQ10 when compared to the labelled quantity. Methods: To test this hypothesis, the group purchased and tested 14 commercially available CoQ10 supplements with each serving containing 100 mg of active, choosing a variety of drug delivery systems (DDS) and also included one in-house product, which contained 70 mg of active. The DDSs examined consisted of 7 soft shell gelatin (SSG) capsules (the most common type available), 3 hard shell gelatin (HSG) capsules, 3 tablets (tab), 1 powder, and 1 suspension. Each DDS was placed into a 500 mL volumetric flask (VF) into an aqueous of 0.1 N HCl acid and 0.1% Tween 80, using a standard FDA dissolution method. To facilitate drug release, the contents were removed from the HSG capsules; the SSG capsules were perforated; and the tabs were broken/crushed. After this, a magnetic stir bar was placed into each flask and all DDS samples were vigorously stirred for 30-45 minutes, including being inverted every 10 minutes to further facilitate dissolution of CoQ10 from each DDS. Filtered samples were obtained and the samples were analyzed by a reverse-phase High Performance Liquid Chromatography that was previously developed by this research group. Results and Conclusions: Only two of the 15 products evaluated had significant availability (mean > 50%) of CoQ10; one soft gelatin capsule (Product A, dissolved a mean of 68.57%), and the suspension (Product K, dissolved a mean of 56.71%). All of the other products averaged less than 4% dissolution of the labelled amount (range of values 0.19% to 3.64%). The in-house formulated HSG capsule (Product Q) released a mean amount equal to 8.11% of label (more than twice the percentage of the poorly performing commercial products). The consistency of the products was also variable, with product A having a range of 1.7 to 192 mg of CoQ10 released; Product K had a range of 35.8 to 76.1 mg of drug released. The group concluded that there are acceptable products available, but that most have significant performance issues.

Cardiovascular disease and cardiac events are common and serious health conditions in the United States. Nutrition therapy can play a significant role in the management and treatment of cardiovascular disease, which includes cardiac events. This study examined the dietary supplement knowledge and recommendations made by registered dietitians (RDs), cardiologists, physician assistants, and nurse practitioners to treat patients after experiencing a cardiac event. Over 75 cardiologists, physician assistants, and nurse practitioners in the Tricities area of Tennessee and 3,000 RDs nationwide were asked to complete a 15-question web-based survey. Over 280 RDs and only one cardiologist responded. Findings suggest RDs are aware of evidence supporting dietary supplementation in the treatment of general heart health and cardiac events. Additionally, RDs make dietary supplement recommendations as treatment for patients who have experienced a cardiac event, specifically omega-3 fatty acids or fish oil, coenzyme Q10, and plant sterols.