No / Background Generation and accumulation of reactive oxygen/nitrogen species in the epidermis of patients with vitiligo has been widely documented. Moreover, semiquinone radical-mediated sensitivity has been shown in blood lymphocytes of these patients. Objectives To determine the possible mechanism behind Q10-induced facial vitiligo. Methods This was a clinical assessment supported by in vivo Fourier transform–Raman spectroscopy and repigmentation. Results Topical Q10 application generated hydrogen peroxide (H2O2) leading in turn to facial vitiligo in susceptible individuals. Proof of the basic result stemmed from reduction of epidermal H2O2 by using narrowband ultraviolet B-activated propseudocatalase PC-KUS in association with cessation of depigmentation and repigmentation of the lost skin colour. Conclusions Over-the-counter availability of Q10-containing topical formulations can be harmful to individuals susceptible to vitiligo.

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.

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.

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.

Temperature dependence of marine plankton respiration is an important factor in understanding the function and changes in the ecosystem of the ocean. The aim of this study is to test the temperature sensitivity (Q10) of plankton respiration. The oxygen optode method was used to measure plankton respiration. Natural water samples from the Baltic Sea was incubated at short (in situ +1, +2, +3°C) and long (in situ +5, +10, +20°C) temperature intervals with influence of dissolved organic matter (DOC). The Arrhenius equation and Q10-model was used to determine the temperature dependence (Q10) of respiration at different temperatures. There was a significant difference in Q10 between short temperature intervals at low temperatures (p=0,008) and long temperature intervals at higher temperatures. There was no significant difference between long and short temperature intervals when DOC was added (p=0,094). A significant effect could be seen with the DOC enrichment at low temperatures, where the Q10-values became significantly lower (p=0,002) after DOC addition. This effect could, however, not be seen at higher temperatures (p=0,117). Together with results from earlier studies it was concluded that the difference in temperature depends on the actual temperature and not the length of the interval. Lowered temperature dependence at raised DOC concentration, was the opposite of what was expected. The results suggest that the importance of temperature for CO2 emissions and development of hypoxia in the sea may have been underestimated.

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.

Sammanfattning Bakgrund:Koenzym Q10 (Q10) syntetiseras i kroppen och återfinns med de högsta koncentrationerna i hjärta, lever och immunförsvarets celler. Det har en viktig roll när det agerar transportör av elektroner i andningskedjan. Q10 har även antioxiderande egenskaper, stärker cellmembran och motverkar fettsyraoxidation i mitokondrien och cellmembran. Nyare studier visar att ett tillskott av Q10 även förbättrar symptomen vid kronisk hjärtsvikt och minskar kardiovaskulära händelser.Vid förhöjda blodfetter är det mest använda läkemedlet statiner. De hämmar kolesterolsyntesen i levern och de påverkar även syntesen av Q10 vilken också sker mevalonatvägen. En av de vanligaste biverkningarna vid statinbehandling är muskelbesvären myopati och myalgi. Studier visar att dåligt fungerande mitokondrier och reducering av Q10 i serum kan relateras till statinbehandling. Syfte:Syftet med detta arbete har varit att undersöka om ett tillskott av Q10 har någon reducerande effekt på smärtan vid statininducerad myopati (SIM).  Metod:Denna litteraturstudie baserades på sex vetenskapliga artiklar sökta via PubMed. Studierna skulle vara randomiserade, dubbelblinda kliniska studier gjorda på människor. Av sökningens 10 träffar erhölls 6 artiklar vilka var relevanta för att besvara denna studiens frågeställning. Resultat:Resultatet visade att Q10 inte har någon större effekt på smärtan vid SIM. Endast 2 av 6 studier visar att Q10 har en god effekt.  Slutsats: För att kunna dra slutsats om Q10 har effekt eller inte vid SIM behövs fler randomiserade placebokontrollerade studier med jämförbara grupper och fler antal deltagare.

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

A distrofia muscular de Duchenne (DMD) é uma doença hereditária, degenerativa e progressiva dos músculos esqueléticos. É causada pela ausência da proteína distrofina e caracterizada pela perda progressiva da força muscular e deterioração da capacidade funcional. Alterações na regulação da homeostase do cálcio, proteólise e alterações metabólicas, especialmente mitocondriais, são parte da patogênese da doença. A coenzima Q (CoQ10), potente antioxidante que participa da atividade da cadeia respiratória, tem sido utilizada em ensaios clínicos, entretanto, não há estudos que evidencie seu comprometimento na DMD. O objetivo deste estudo foi avaliar a CoQ10 e a da atividade da cadeia respiratória em fragmentos de biópsia muscular de pacientes com DMD e sua correlação com parâmetros clínicos e a capacidade funcional. O estudo constitui de uma etapa retrospectiva, onde foram analisadas 22 biópsias musculares de pacientes com DMD, e outra prospectiva, onde foram avaliados dez pacientes com DMD. Dez pacientes controles foram utilizados nas duas etapas do estudo. A concentração da CoQ10 foi realizada através da técnica de cromatografia líquida de alta performance de fase reversa. As atividades das enzimas da cadeia respiratória foram medidas através de técnicas espectrofotométricas. A capacidade funcional foi mensurada através das escalas Medida da Função Motora (MFM) e Escala de Avaliação para deambulantes North Star (NSAA), e dos testes cronometrados: tempo para percorrer 10 metros (T10), tempo para realizar a manobra de Gowers (TGowers) e teste da caminhada dos 6 minutos (TC6min). Fase retrospectiva: a média de idade dos pacientes com DMD foi de 6,9 anos, (DP ±2,4) e controles de 8 anos, (DP ±2,69). A dosagem média de CoQ10 nos fragmentos de pacientes com DMD foi de 8,6 µg/g de tecido (DP ±3,9) e nos fragmentos dos controles foi de 31,6 µg/g de tecido (DP ±6,9). A média da área ocupada por fibras musculares nos pacientes com DMD foi de 27,3% (DP ±14,2%) e nos controles foi de 89,2% (DP ±3,3%). Evidenciou-se alta correlação entre aquantidade de CoQ10 e a área relativa ocupada por fibras musculares (r= 0,767 e p= 0,016). As atividades dos complexos enzimáticos da cadeia respiratória dos pacientes com DMD não demonstraram deficiência. Já o resultado do ensaio conjunto dos complexos II+III, encontra-se significativamente reduzido nos pacientes com DMD. Etapa prospectiva: a média de idade dos pacientes com DMD foi de 6,5 anos, (DP ±2,4). A dosagem média de CoQ10 nos fragmentos de pacientes com DMD foi de 12,6 µg/g de tecido (DP ±5,1). A média da área ocupada por fibras musculares nos pacientes com DMD foi de 40,3% (DP ±20,4%). Houve alta correlação entre a quantidade de CoQ10 e a área relativa ocupada por fibras musculares (r= 0,690 e p= 0,058). A correlação da dosagem da CoQ10 com os instrumentos de avaliação da capacidade funcional foi alta com o TGowers e moderada com MFM total e dimensões 1 e 2, NSAA, T10 e TC6min. Em relação à área relativa de fibras musculares, houve moderada correlação com a dimensão 1 da MFM e com o TGowers. Não houve correlação da CoQ10 e da área relativa ocupada por fibras musculares com os parâmetros clínicos: idade no momento da biópsia, idade do início dos sintomas e tempo de evolução da doença. No presente estudo, concluímos que existe uma deficiência secundária de CoQ10 em pacientes com DMD, a qual contribui para entender a fisiopatologia da doença e com grande relevância para as propostas terapêuticas. / Duchenne muscular dystrophy (DMD) is a hereditary, degenerative and progressive skeletal muscles disease. It is caused by the absence of the protein dystrophin and characterized by progressive loss of muscle strength and deterioration of functional capacity. Alterations in the regulation of calcium homeostasis, proteolysis and metabolic abnormalities, especially mitochondrial dysfunction, are part of the pathogenesis of the disease. Coenzyme Q (CoQ10), a potent antioxidant that participates in respiratory chain activity, has been used in clinical trials, however, there are no studies showing its involvement in DMD. The purpose of this study was to investigate CoQ10 content and respiratory chain activity in muscle biopsy of patients with DMD and its correlation with clinical parameters and functional capacity. The study consisted of a retrospective phase, in which 22 muscle biopsies from patients with DMD were analyzed, and a prospective phase, where ten patients with DMD were evaluated. The same control group of ten patients were used in the two phases of the study. The concentration of CoQ10 was measured using the reverse phase high performance liquid chromatography technique. Activities of the respiratory chain enzymes were measured by spectrophotometry. The functional capacity was evaluated using the Motor Function Measurement (MFM) and North Star Ambulatory Assessment (NSAA) and the following timed tests: to run 10 meters (T10), to perform the Gowers maneuver (TGowers) and the 6-minute walk test (6MWT). Retrospective phase: the mean age of patients with DMD was 6.9 years (SD ± 2.4) and of controls was 8 years (SD ± 2.69). The mean CoQ10 content in fragments from patients with DMD was 8.6 ?g / g tissue (DP ± 3.9) and in fragments from controls was 31.6 ?g / g tissue (DP ± 6.9). The mean area occupied by muscle fibers in patients with DMD was 27.3% (SD ± 14.2%) and in controls was 89.2% (SD ± 3.3%). There was a high correlation between the amount of CoQ10 and the relative area occupied by muscle fibers (r= 0.767 and p= 0.016). The activities of respiratory chain enzymes from patients with DMD were not deficient. On the other hand, the results of the combined analysis of complexes II + III were significantly reduced in patients with DMD. Prospective phase: the mean age of patients with DMD was 6.5 years (SD ± 2.4). The mean CoQ10 content in fragments from patients with DMD was 12.6 ?g / g tissue (SD ± 5.1). The mean area occupied by muscle fibers in patients with DMD was 40.3% (SD ± 20.4%). There was a high correlation between the amount of CoQ10 and the relative area occupied by muscle fibers (r= 0.690 and p= 0.058). The correlation between the amount of CoQ10 and the functional capacity assessment instruments was high forTGowers and moderate for MFM total and dimensions 1 and 2, NSAA, T10 andd TC6min. Regarding the relative area of muscle fibers, there was a moderate correlation with MFM dimension 1 (standing position and transfers) and TGowers. There was no correlation between CoQ10 and relative area occupied by muscle fibers with clinical parameters: age at time of biopsy, age of onset of symptoms and time of disease progression. In the present study, we conclude that there is a secondary deficiency of CoQ10 in patients with DMD, which contributes for the understanding of its physiopathology and is relevant for therapy.

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)