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1.
J Biochem Mol Toxicol ; 33(11): e22398, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31557371

RESUMO

Cyclophosphamide (CTX) has been broadly used in the clinic for the treatment of autoimmune disorders and ovarian cancer. The process of chemotherapy has significant toxicity in the reproductive system as it has detrimental effects on folliculogenesis, which leads to an irreversible premature ovarian failure (POF). Coenzyme Q10 (CoQ10) has positive impacts on the reproductive system due to its antioxidant properties, protecting the cells from free-radical oxidative damage and apoptosis. However, little is known about the possible synergistic effect of CTX and CoQ10 on the expression of genes involved in folliculogenesis, such as proliferation cell nuclear antigen (PCNA) and follicle-stimulating hormone receptor (FSHR). A total of 32 NMRI mice were applied and divided into four groups, including healthy control, CTX, CTX + CoQ10, and CoQ10 groups. The effects of CoQ10 on CTX-induced ovarian injury and folliculogenesis were examined by histopathological and real-time quantitative reverse transcription-polymerase chain reaction analyses. The rates of fertilization (in vitro fertilization), embryo development, as well as the level of reactive oxygen species (ROS) in metaphase II (MII) mouse oocytes after PMSG/HCC treatment were also assessed. Results showed that the treatment with CTX decreased the mRNA expression of PCNA and FSHR, IVF rate, and embryo development whereas the application of CoQ10 successfully reversed those factors. CoQ10 administration significantly enhanced histological morphology and decreased ROS levels and the number of atretic follicles in the ovary of CTX-treated mice. In conclusion, it seems that the protective effect of CoQ10 is exerted via the antioxidant and proliferative properties of this substance on CTX-induced ovarian damage.


Assuntos
Antioxidantes/farmacologia , Ciclofosfamida/farmacologia , Insuficiência Ovariana Primária/induzido quimicamente , Antígeno Nuclear de Célula em Proliferação/genética , Receptores do FSH/genética , Ubiquinona/análogos & derivados , Regulação para Cima/efeitos dos fármacos , Animais , Antioxidantes/administração & dosagem , Ciclofosfamida/administração & dosagem , Sinergismo Farmacológico , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Fertilização In Vitro/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Modelos Animais , Oócitos/metabolismo , Ovário/efeitos dos fármacos , Ovário/patologia , Indução da Ovulação , RNA Mensageiro/genética , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ubiquinona/administração & dosagem , Ubiquinona/farmacologia
2.
Toxicol Ind Health ; 35(7): 466-481, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31364507

RESUMO

The present study was conducted to investigate the antioxidant, histomorphometric, histochemical, immunohistochemical, biochemical, and cytological effects of coenzyme Q10 (CoQ10) against bisphenol-A (BPA)-induced testicular toxicity in rats. A total of 40 adult male Wistar rats were divided into five equal groups. The control group remained untreated. The vehicle control group was administered corn oil (2 ml/kg/day), the BPA group was given BPA (100 mg/kg/day), the CoQ10 group was supplemented with CoQ10 (10 mg/kg/day), and the rats in the CoQ10-BPA group received CoQ10 (10 mg/kg/day) followed by BPA (100 mg/kg/day) 1 h later. The treatments were administered by oral gavage for 14 days. Results showed that the seminiferous tubule diameters (STDs) and seminiferous epithelium heights (SEHs) at stages VII-VIII and XII-XIV, number of undifferentiated embryonic cell transcription factor-1 (UTF-1) positive cells per tubule, UTF-1 positive tubules (%), plasma glutathione (GSH), and serum superoxide dismutase activities, testicular GSH activity and sperm viability (%) decreased whereas the number of terminal dUTP nick end labeling (TUNEL) positive cells per tubule, TUNEL positive tubules (%), testicular and serum malondialdehyde (MDA) levels, and the rate of mid-piece sperm abnormality increased in the BPA administered group. However, while the STDs at stages VII-VIII and XII-XIV, SEHs at stages VII-VIII, plasma GSH, and serum SOD activities increased, serum MDA level decreased in the CoQ10-BPA group. In conclusion, these results suggest a protective effect of CoQ10 against BPA-induced testicular toxicity in rats.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Fenóis/efeitos adversos , Testículo/efeitos dos fármacos , Testículo/patologia , Ubiquinona/análogos & derivados , Animais , Glutationa/metabolismo , Masculino , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Fatores de Transcrição/biossíntese , Ubiquinona/administração & dosagem , Ubiquinona/farmacologia
3.
Nutrients ; 11(7)2019 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-31330878

RESUMO

Maternal smoking leads to glucose and lipid metabolic disorders and hepatic damage in the offspring, potentially due to mitochondrial oxidative stress. Mitoquinone mesylate (MitoQ) is a mitochondrial targeted antioxidant with high bioavailability. This study aimed to examine the impact of maternal cigarette smoke exposure (SE) on offspring's metabolic profile and hepatic damage, and whether maternal MitoQ supplementation during gestation can affect these changes. Female Balb/c mice (eight weeks) were either exposed to air or SE for six weeks prior to mating and throughout gestation and lactation. A subset of the SE dams were supplied with MitoQ in the drinking water (500 µmol/L) during gestation and lactation. Intraperitoneal glucose tolerance test was performed in the male offspring at 12 weeks and the livers and plasma were collected at 13 weeks. Maternal SE induced glucose intolerance, hepatic steatosis, mitochondrial oxidative stress and related damage in the adult offspring. Maternal MitoQ supplementation reduced hepatic mitochondrial oxidative stress and improved markers of mitophagy and mitochondrial biogenesis. This may restore hepatic mitochondrial health and was associated with an amelioration of glucose intolerance, hepatic steatosis and pathological changes induced by maternal SE. MitoQ supplementation may potentially prevent metabolic dysfunction and hepatic pathology induced by intrauterine SE.


Assuntos
Fígado Gorduroso/induzido quimicamente , Exposição Materna , Síndrome Metabólica/induzido quimicamente , Compostos Organofosforados/farmacologia , Poluição por Fumaça de Tabaco/efeitos adversos , Ubiquinona/análogos & derivados , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Feminino , Lactação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias Hepáticas/fisiologia , Compostos Organofosforados/administração & dosagem , Estresse Oxidativo , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ubiquinona/administração & dosagem , Ubiquinona/farmacologia
4.
Diabetes Metab Syndr ; 13(2): 1179-1185, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31336462

RESUMO

AIMS: This meta-analysis study was carried out to assess the effects of coenzyme Q10 supplementation on body weight and body mass index of patients in randomized controlled clinical trial studies. MATERIALS AND METHODS: A comprehensive systematic search of literature was performed through ISI web of sciences, PubMed, Scopus and Cochrane library databases up to February 2018 which was supplemented by manual search of the references list of included studies. From a total of 1579 identified articles, only 17 trials with 14 and 14 effect-sizes were included for pooling the effects of co-enzyme Q10 supplementation on body weight and body mass index, respectively. RESULTS: Results of random-effect size meta-analysis showed that supplementation with coenzyme Q10 had no significant decreasing effects on body weight (WMD: 0.28 kg; 95% CI = -0.91, 1.47; P = 0.64) and BMI (WMD: -0.03; 95% CI = -0.4, 0.34; P = 0.86) of study participants. Subgroup analysis revealed that dosage of Q10 and trial duration could not differ the results of Q10 supplementation. CONCLUSION: Results of this meta-analysis study failed to show any beneficial effect of coenzyme Q10 supplementation on body weight and BMI of patients in clinical trial studies.


Assuntos
Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Suplementos Nutricionais , Ubiquinona/análogos & derivados , Humanos , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ubiquinona/administração & dosagem
5.
Vopr Pitan ; 88(2): 40-49, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31233687

RESUMO

Nowdays, much attention is paid to the study of disorders of immune regulation and methods of effective immune correction in athletes. In this regard, the use of specialized sport foods (SSF), containing nutrients with immunomodulatory properties, is of particular relevance in youth sports. The aim of the work is to study the immunomodulating activity of L-carnitine and coenzyme Q10 in junior athletes during the training period. Material and methods. The object of the study were 30 junior athletes (masters of sports and candidates for masters of sports in swimming) aged 14-18 years, including 9 girls and 21 boys. Athletes were divided into 3 groups of 10 people each. Athletes of the 1st and 2nd main groups received L-carnitine (600 mg per day) and coenzyme Q10 (60 mg/day), respectively, for 4 weeks in addition to the basic diet. The dosage of SSF used in the study was 200% of the adequate level of consumption and did not exceed the upper permissible level of consumption. Athletes of the 3rd group (control) received only basic diet without sports' nutrition. Examination of athletes of all groups was performed at the beginning and after 4 weeks of the observation period. Results and discussion. As a result of a comprehensive survey of junior athletes, the positive effect of L-carnitine intake on erythrocyte hemoglobin content (30.2±0.4 vs 28.3±0.3 pg at the beginning) was observed. The relative content of basophilic leukocytes in athletes of the main groups statistically significantly decreased by the end of the observation period: in the L-carnitine group, from 0.64±0.05 to 0.45±0.04%, in the coenzyme Q10 group, from 0.66±0.07 to 0.50±0.04%, which indicated an increase in the body's resistance to allergic reactions. Conclusion. The biomarkers of the immunotropic effect of L-carnitine and coenzyme Q10 are a decrease in the expression of the apoptotic marker CD95/Fas on peripheral blood lymphocytes and suppression of the production of pro-inflammatory cytokines synthesized by Th1-lymphocytes with switching the response to humoral immunity. An evidence base for the effectiveness of the use of L-carnitine and coenzyme Q10 in sports nutrition for restoring immune dysfunction and adaptive potential of junior athletes has been provided.


Assuntos
Atletas , Carnitina/administração & dosagem , Imunidade Humoral/efeitos dos fármacos , Imunomodulação/efeitos dos fármacos , Células Th1 , Ubiquinona/análogos & derivados , Receptor fas , Adolescente , Feminino , Hemoglobinas/imunologia , Hemoglobinas/metabolismo , Humanos , Contagem de Leucócitos , Masculino , Estado Nutricional , Natação , Células Th1/imunologia , Células Th1/metabolismo , Ubiquinona/administração & dosagem , Receptor fas/sangue , Receptor fas/imunologia
6.
Drug Dev Ind Pharm ; 45(9): 1451-1458, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31216907

RESUMO

Objective: The aim of this study was to develop a coenzyme Q10 nanoemulsion cream, characterize and to determine the influence of omega fatty acids on the delivery of coenzyme Q10 across model skin membrane via ex vivo and in silico techniques. Methods: Coenzyme Q10 nanoemulsion creams were prepared using natural edible oils such as linseed, evening primrose, and olive oil. Their mechanical features and ability to deliver CoQ10 across rat skin were characterized. Computational docking analysis was performed for in silico evaluation of CoQ10 and omega fatty acid interactions. Results: Linseed, evening primrose, and olive oils each produced nano-sized emulsion creams (343.93-409.86 nm) and exhibited excellent rheological features. The computerized docking studies showed favorable interactions between CoQ10 and omega fatty acids that could improve skin permeation. The three edible-oil nanoemulsion creams displayed higher ex vivo skin permeation and drug flux compared to the liquid-paraffin control cream. The linseed oil formulation displayed the highest skin permeation (3.97 ± 0.91 mg/cm2) and drug flux (0.19 ± 0.05 mg/cm2/h). Conclusion: CoQ10 loaded-linseed oil nanoemulsion cream displayed the highest skin permeation. The highest permeation showed by linseed oil nanoemulsion cream may be due to the presence of omega-3, -6, and -9 fatty acids which might serve as permeation enhancers. This indicated that the edible oil nanoemulsion creams have potential as drug vehicles that enhance CoQ10 delivery across skin.


Assuntos
Portadores de Fármacos/química , Ácidos Graxos Insaturados/química , Creme para a Pele/farmacocinética , Ubiquinona/análogos & derivados , Administração Cutânea , Animais , Simulação por Computador , Composição de Medicamentos , Emulsões , Nanopartículas/química , Permeabilidade , Ratos , Pele/efeitos dos fármacos , Pele/metabolismo , Absorção Cutânea , Creme para a Pele/administração & dosagem , Ubiquinona/administração & dosagem , Ubiquinona/farmacocinética
7.
J Exp Clin Cancer Res ; 38(1): 186, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31068208

RESUMO

BACKGROUND: Breast cancer is the most prevalent cancer among women. In triple-negative breast cancer (TNBC) cells, a novel quinone derivative, coenzyme Q0 (CoQ0), promotes apoptosis and cell-cycle arrest. This study explored the anti-epithelial-mesenchymal transition (EMT) and antimetastatic attributes of CoQ0 in TNBC (MDA-MB-231). METHODS: Invasion, as well as MTT assays were conducted. Lipofectamine RNAiMAX was used to transfect cells with ß-catenin siRNA. Through Western blotting and RT-PCR, the major signaling pathways' protein expressions were examined, and the biopsied tumor tissues underwent immunohistochemical and hematoxylin and eosin staining as well as Western blotting. RESULTS: CoQ0 (0.5-2 µM) hindered tumor migration, invasion, and progression. Additionally, it caused MMP-2/- 9, uPA, uPAR, and VEGF downregulation. Furthermore, in highly metastatic MDA-MB-231 cells, TIMP-1/2 expression was subsequently upregulated and MMP-9 expression was downregulated. In addition, CoQ0 inhibited metastasis and EMT in TGF-ß/TNF-α-stimulated non-tumorigenic MCF-10A cells. Bioluminescence imaging of MDA-MB-231 luciferase-injected live mice demonstrated that CoQ0 significantly inhibited metastasis of the breast cancer to the lungs and inhibited the development of tumors in MDA-MB-231 xenografted nude mice. Silencing of ß-catenin with siRNA stimulated CoQ0-inhibited EMT. Western blotting as well as histological analysis established that CoQ0 reduced xenografted tumor development because apoptosis induction, cell-cycle inhibition, E-cadherin upregulation, ß-catenin downregulation, and metastasis and EMT regulatory protein modulation were observed. CONCLUSIONS: CoQ0 inhibited the progression of metastasis as well as EMT (in vitro and in vivo). The described approach has potential in treating human breast cancer metastasis.


Assuntos
Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Ubiquinona/administração & dosagem , Animais , Antígenos CD/genética , Apoptose/efeitos dos fármacos , Caderinas/genética , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Humanos , Metaloproteinase 9 da Matriz/genética , Camundongos , NF-kappa B/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio , Transdução de Sinais , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/genética
8.
Parasitol Int ; 71: 106-120, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30981893

RESUMO

In animal model of experimental cerebral malaria (ECM), the genesis of neuropathology is associated with oxidative stress and inflammatory mediators. There is limited progress in the development of new approaches to the treatment of cerebral malaria. Here, we tested whether oral supplementation of Coenzyme Q10 (CoQ10) would offer protection against oxidative stress and brain associated inflammation following Plasmodium berghei ANKA (PbA) infection in C57BL/6 J mouse model. For this purpose, one group of C57BL/6 mice was used as control; second group of mice were orally supplemented with 200 mg/kg CoQ10 and then infected with PbA and the third group was PbA infected alone. Clinical, biochemical, immunoblot and immunological features of ECM was monitored. We observed that oral administration of CoQ10 for 1 month and after PbA infection was able to improve survival, significantly reduced oedema, TNF-α and MIP-1ß gene expression in brain samples in PbA infected mice. The result also shows the ability of CoQ10 to reduce cholesterol and triglycerides lipids, levels of matrix metalloproteinases-9, angiopoietin-2 and angiopoietin-1 in the brain. In addition, CoQ10 was very effective in decreasing NF-κB phosphorylation. Furthermore, CoQ10 supplementation abrogated Malondialdehyde, and 8-OHDG and restored cellular glutathione. These results constitute the first demonstration that oral supplementation of CoQ10 can protect mice against PbA induced oxidative stress and neuro-inflammation usually observed in ECM. Thus, the need to study CoQ10 as a candidate of antioxidant and immunomodulatory molecule in ECM and testing it in clinical studies either alone or in combination with antimalaria regimens to provide insight into a potential translatable therapy.


Assuntos
Encéfalo/imunologia , Fatores Imunológicos/administração & dosagem , Inflamação/prevenção & controle , Malária Cerebral/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Ubiquinona/análogos & derivados , Administração Oral , Animais , Encéfalo/patologia , Quimiocina CCL4/genética , Modelos Animais de Doenças , Feminino , Glutationa/metabolismo , Inflamação/patologia , Malária Cerebral/imunologia , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Fosforilação , Plasmodium berghei , Fator de Necrose Tumoral alfa/genética , Ubiquinona/administração & dosagem
9.
Biomed Res Int ; 2019: 7167525, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863780

RESUMO

Effects of in ovo injection of Q10 on hatchability, performance (feed intake (FI), body weight gain (BWG), feed/gain ratio (F/G)) traits, and immune status of Ross × Ross 308 broiler chicks, hatched from eggs laid by a 38-week-old breeder flock, were determined through 42 days after hatch. Eggs containing live embryos were injected in the amnion with 0.1 and 0.2 mL Q10 solution on day 18 of incubation. Two controls groups were included as sham and/or as an uninjected group. At 28 and 42 days of age, performance traits, serum enzyme activity, weights of immune organs, and serum antibody titer of viral diseases were determined. Results were shown that hatchability % increased by Q10 on average of 6.54% (P≤0.025) and body weight/egg weight after hatching increased up to 4.74% (P≤0.002), compared with uninjected and sham controls. Injection of Q10 at different levels led to significant increases (P≤0.001) in performance traits all over the rearing period (P<0.05). Weight of immune organs significantly improved compared to uninjected and sham controls (P<0.05). In addition, serum antibody titers of viral diseases as well as serum enzyme activity of AST, ALT, CAT, and SOD were significantly changed by Q10 treated groups than controls (P≤0.01). In conclusion, in ovo injection of Q10 at levels of 0.1 and 0.2 mL led to significant increases in hatchability%, internal egg characteristics, and performance parameters as well as serum enzyme activity, weight of immune organs, and serum antibody titer of ND, AI, and IBD diseases.


Assuntos
Galinhas/crescimento & desenvolvimento , Ovos , Óvulo/efeitos dos fármacos , Ubiquinona/análogos & derivados , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Injeções , Fígado/efeitos dos fármacos , Fígado/crescimento & desenvolvimento , Fígado/metabolismo , Óvulo/crescimento & desenvolvimento , Ubiquinona/administração & dosagem
10.
Nutrients ; 11(3)2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30823449

RESUMO

Coenzyme Q10 (CoQ10) is a natural compound with potent antioxidant properties. Its provision through diet does not always allow adequate levels in the human body, and supplementation is often necessary. This bioavailability study intended to explore the plasma concentration levels of a novel CoQ10 oral preparation (COQUN®, Coenzyme Q10 Miniactives Retard 100 mg capsules) mimicking assumption on a regular basis. Twenty-four healthy adults tested a single dose of CoQ10 100 mg in one day to assess bioavailability. After a one week wash-out period, they were randomly assigned (1:1) to continuous administration for four weeks: Group A (n = 12) 100 mg once a day (OD); and Group B (n = 12) 100 mg twice a day (BID). During the single dose phase, Cmax was observed at 4 h, and the mean values of AUCt and Tmax were 8754 µg/mL·h and 4.29 h, respectively. The multiple dose phase showed increasing plasma levels up to 7 days after the start of administration, and sustained high concentrations during the all administration period. No relevant adverse events were reported. These results show that Miniactives® technology can release CoQ10 to allow high constant blood concentrations without a sharp decrease. This may be the first step of evidence for a potential new antioxidative treatment in human chronic diseases deserving high CoQ10 levels.


Assuntos
Ubiquinona/análogos & derivados , Vitaminas/administração & dosagem , Vitaminas/farmacocinética , Administração Oral , Adulto , Disponibilidade Biológica , Preparações de Ação Retardada , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ubiquinona/administração & dosagem , Ubiquinona/farmacocinética
11.
Yakugaku Zasshi ; 139(3): 341-347, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30828009

RESUMO

Preventive medicine and anti-aging medicine have received much attention recently due to an increase in the proportion of elderly people in the population, and to an increase in patients with lifestyle diseases. Oxidative stress is involved in the onset of lifestyle diseases, and various antioxidant supplements and antioxidant-fortified functional foods have recently become available. Many epidemiological studies have shown relationships between the consumption of polyphenol and carotenoid-rich foods and the prevention of lifestyle diseases. We have focused on the absorption mechanism of these food components that show low bioavailability, and have made efforts to improve their poor absorption based on their pharmacokinetic properties. In this report, as examples, we describe the enhancement of the absorption of coenzyme Q10 (CoQ10) and lutein. To improve the absorption of CoQ10, we focused on the component of emulsion. We found that a higher plasma concentration of CoQ10 could be obtained by creating an emulsion containing a surfactant with a higher hydrophile-lipophile balance (HLB) value. For the improvement of lutein absorption, we prepared a solid dispersion and self-emulsifying drug delivery system. It was shown that the plasma concentrations of lutein in these two formulation groups were increased compared with that in the powder group. The absorption of lutein was also evaluated by its cumulative amount in the lymph system. Our data showed that lutein is transferred from the small intestine into the lymph stream, rather than into the blood stream. Further investigations to improve the absorption of these components are in progress.


Assuntos
Antioxidantes/administração & dosagem , Antioxidantes/farmacocinética , Suplementos Nutricionais , Alimento Funcional , Luteína/administração & dosagem , Luteína/farmacocinética , Ubiquinona/análogos & derivados , Animais , Disponibilidade Biológica , Carotenoides/administração & dosagem , Carotenoides/farmacocinética , Sistemas de Liberação de Medicamentos , Emulsões , Alimento Funcional/análise , Humanos , Interações Hidrofóbicas e Hidrofílicas , Absorção Intestinal , Estilo de Vida , Sistema Linfático/metabolismo , Estresse Oxidativo , Polifenóis/administração & dosagem , Polifenóis/farmacocinética , Ratos , Tensoativos , Ubiquinona/administração & dosagem , Ubiquinona/farmacocinética
12.
Drug Discov Ther ; 13(1): 38-46, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30880321

RESUMO

Heart failure with preserved ejection fraction (HFpEF) is a leading cause of morbidity and mortality without an established treatment. Diastolic dysfunction, the hallmark of HFpEF, is associated with altered myocardial bioenergetics. No previous study has examined the effects of coenzyme Q10 (CoQ10) on left ventricle (LV) diastolic function in patients with HFpEF. We investigated whether CoQ10 could improve LV diastolic function in patients with HFpEF. We performed a randomized controlled trial (RCT) using pretest and posttest control groups of 30 patients with HFpEF. The patients received either CoQ10 100 mg three times a day or no CoQ10 in addition to routine treatment for 30 days. Echocardiographic study was performed at baseline and follow-up. LV diastolic function was evaluated by two dimensional and Doppler echocardiography as follows; average E/e׳, septal and lateral e׳velocity, and left atrium volume index (LAVI). A total of 28 patients completed the study. A statistically significant improvement was observed in the CoQ10 treatment group in terms between groups (∆E/e׳ ‒ 3.6 vs. ‒ 2.4; p = 0.28) and (∆LAVI ‒ 5.4 vs. ‒ 4.4; p = 0.83). Short term CoQ10 supplementation provided no additional benefits in improving LV diastolic function in patients with HFpEF.


Assuntos
Diástole/efeitos dos fármacos , Suplementos Nutricionais , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/tratamento farmacológico , Volume Sistólico/efeitos dos fármacos , Ubiquinona/análogos & derivados , Idoso , Diástole/fisiologia , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico/fisiologia , Ubiquinona/administração & dosagem , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Esquerda/fisiologia
13.
Biomed Res Int ; 2019: 1970878, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30723735

RESUMO

Nutritional approaches to improve dyslipidemias have been recently developed, but evidences on different medical foods are often incomplete. The main aim of our study was to evaluate the effects on endothelial function, lipid profile, and glucose metabolism of two different combinations of nutraceuticals, first one containing Bergavit (200 mg Citrus bergamia), Omega-3 (400 mg), Crominex 3+ (10 mcg trivalent chromium), and red yeast rice (100 mg; 5 mg monacolin K) and second one containing red yeast rice (200 mg; 3 mg monacolin K), Berberine (500 mg), Astaxanthin (0.5 mg), folic acid (200 mcg), Coenzyme Q10 (2 mg), and Policosanol (10 mg). Fifty subjects affected by dyslipidemia not requiring statin treatment were enrolled in this randomized, blind, controlled trial and submitted to blood sampling for lipid and glucose profiles and instrumental evaluation of endothelial function before and after 6 weeks of treatment with nutraceuticals. Both nutraceutical combinations improved the lipid profile; the nutraceutical containing 5 mg of monacolin K, 200 mg of the extract Citrus bergamia, 400 mg of Omega-3, and 10 mcg of trivalent chromium entailed a significant improvement of endothelial function with enhanced cholesterol lowering effect. In conclusion, this study confirms the positive effect of functional food on lipid profile and endothelial function in absence of major undesirable effects.


Assuntos
Dislipidemias/dietoterapia , Células Endoteliais/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Adulto , Idoso , Produtos Biológicos/administração & dosagem , Cromo/administração & dosagem , Citrus , Suplementos Nutricionais/classificação , Dislipidemias/metabolismo , Dislipidemias/patologia , Células Endoteliais/metabolismo , Ácidos Graxos Ômega-3/administração & dosagem , Álcoois Graxos/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ubiquinona/administração & dosagem , Ubiquinona/análogos & derivados , Xantofilas/administração & dosagem
14.
Eur J Ophthalmol ; 29(2): 196-201, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29869538

RESUMO

PURPOSE:: To evaluate the levels of oxidative stress markers such as superoxide dismutase and malondialdehyde in eyes with pseudo-exfoliative glaucoma treated with and without topical coenzyme Q10 (CQ10) and vitamin E (Coqun drop). METHODS:: This prospective, randomized clinical study was conducted on 64 eyes of 64 patients. All patients underwent phacoemulsification and intraocular lens implantation surgery. Aqueous humor samples were aspirated from the anterior chamber at the beginning of cataract surgery. The pseudo-exfoliative glaucoma + Coqun group received topical Coqun (100 mg CQ10, 500 mg Vitamin E TPGS) twice daily for 1 month preoperatively, while the pseudo-exfoliative glaucoma group consisted of pseudo-exfoliative glaucoma cases who had not taken Coqun. Pseudo-exfoliation syndrome cases formed the pseudo-exfoliation syndrome group. The main outcomes were the superoxide dismutase and malondialdehyde levels of aqueous humor in both groups. RESULTS:: The mean aqueous humor superoxide dismutase level was significantly higher in the pseudo-exfoliative glaucoma group than in pseudo-exfoliative glaucoma + Coqun and pseudo-exfoliation syndrome groups (p < 0.001, p = 0.004, respectively). Also, the mean aqueous humor superoxide dismutase level was significantly lower in the pseudo-exfoliation syndrome group than in pseudo-exfoliative glaucoma + Coqun group (p = 0.009). The mean malondialdehyde levels showed no significant difference between the groups (p > 0.05 for all). CONCLUSION:: Our study showed lower aqueous humor level of superoxide dismutase in pseudo-exfoliation syndrome patients compared to pseudo-exfoliative glaucoma patients. Significantly lower superoxide dismutase level was observed in pseudo-exfoliative glaucoma patients who received topical Coqun compared to pseudo-exfoliative glaucoma patients without Coqun treatment. No significant change was observed on the malondialdehyde level during 1-month follow-up period.


Assuntos
Síndrome de Exfoliação/metabolismo , Pressão Intraocular/fisiologia , Estresse Oxidativo/fisiologia , Ubiquinona/análogos & derivados , Vitamina E/administração & dosagem , Administração Tópica , Idoso , Humor Aquoso/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Síndrome de Exfoliação/tratamento farmacológico , Síndrome de Exfoliação/fisiopatologia , Feminino , Humanos , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Estudos Prospectivos , Superóxido Dismutase/metabolismo , Ubiquinona/administração & dosagem , Vitaminas/administração & dosagem
15.
Exp Clin Endocrinol Diabetes ; 127(5): 311-319, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29365333

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a disease associated with increased oxidative stress which results from mitochondrial dysfunction. Coenzyme Q10 (CoQ10) is an essential antioxidant for energy production in mitochondria. The purpose of this randomized double-blind clinical trial study was to evaluate the effects of CoQ10 supplementation on serum values of gamma-glutamyl transferase (GGT), pseudocholinesterase (PchE), bilirubin, ferritin, and high-sensitivity c-reactive protein (hs-CRP) and metabolic syndrome biomarkers in women with T2DM. MATERIAL & METHODS: Eighty women with T2DM enrolled in this study. Thirty six of them were randomized in the drug group (receiving 100 mg/day of CoQ10) and 44 women were randomized in placebo group. Intervention was continued for 12 weeks. In both groups 35 subjects finished the study and were included in the analysis. Serum levels of the variables were measured before and after supplementation. RESULTS: Serum values of FBS (P=0.039), HOMA-IR (P=0.01), ferritin (P<0.001), total cholesterol (TC) (P=0.006), LDL-C (P=0.007) decreased and HDL-C (P=0.02) increased significantly in the drug group after intervention. Serum levels of triglyceride (P=0.09) decreased marginally in CoQ10 group. CONCLUSIONS: The results of the current study had shown that after supplementation with 100 mg/day of CoQ10 for 12 weeks, serum values of FBS, HOMA-IR, TC, LDL-C and ferritin were decreased and values of HDL-C were increased in women with T2DM.


Assuntos
Bilirrubina/sangue , Glicemia/efeitos dos fármacos , Butirilcolinesterase/efeitos dos fármacos , Proteína C-Reativa/efeitos dos fármacos , HDL-Colesterol/efeitos dos fármacos , LDL-Colesterol/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ferritinas/efeitos dos fármacos , Ubiquinona/análogos & derivados , Adulto , Butirilcolinesterase/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Suplementos Nutricionais , Feminino , Ferritinas/sangue , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento , Ubiquinona/administração & dosagem , Ubiquinona/farmacologia , gama-Glutamiltransferase/sangue , gama-Glutamiltransferase/efeitos dos fármacos
16.
Nutrition ; 57: 133-140, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30153575

RESUMO

OBJECTIVES: Bioavailability of supplements with coenzyme Q10 (CoQ10) in humans seems to depend on the excipients of formulations and on physiological characteristics of the individuals. The aim of this study was to determine which factors presented in CoQ10 supplements affect the different response to CoQ10 in humans. METHODS: We tested seven different supplement formulations containing 100 mg of CoQ10 in 14 young, healthy individuals. Bioavailability was measured as area under the curve of plasma CoQ10 levels over 48 h after ingestion of a single dose. Measurements were repeated in the same group of 14 volunteers in a double-blind crossover design with a minimum of 4 wk washout between intakes. RESULTS: Bioavailability of the formulations showed large differences that were statistically significant. The two best absorbable formulations were soft-gel capsules containing ubiquinone (oxidized CoQ10) or ubiquinol (reduced CoQ10). The matrix used to dissolve CoQ10 and the proportion and addition of preservatives such as vitamin C affected the bioavailability of CoQ10. Although control measurements documented that all formulations contained 100 mg of either CoQ10 or ubiquinol, some of the participants showed high and others lower capacity to reach high increase of CoQ10 in blood, indicating the participation of individual unknown physiological factors. CONCLUSION: This study highlights the importance of individually adapted selection of best formulations to reach the highest bioavailability of CoQ10 in humans.


Assuntos
Suplementos Nutricionais , Portadores de Fármacos , Lipídeos , Ubiquinona/administração & dosagem , Administração Oral , Adolescente , Adulto , Área Sob a Curva , Disponibilidade Biológica , Cápsulas , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Solubilidade , Ubiquinona/análogos & derivados , Ubiquinona/química , Ubiquinona/farmacocinética , Adulto Jovem
17.
Nutr Neurosci ; 22(9): 607-615, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29298622

RESUMO

Backgrounds and aims: Migraine and inflammation are correlated. Coenzyme Q10 (CoQ10) as an anti-inflammatory agent has shown useful effects in other diseases. The present study aimed to assess the effect of CoQ10 supplementation on inflammation and clinical features of migraine. Methods: This randomized double-blind placebo-controlled clinical trial was conducted among 45 non-menopausal women aged 18-50 years, diagnosed for episodic migraine according to the International Headache Society. After one month run-in period, subjects received CoQ10 (400 mg/day CoQ10, n = 23) or placebo (wheat starch, n = 22) for three months. All the patients got prophylactic medication too. Serum CoQ10 concentration, Calcitonin gene-related peptide (CGRP), interleukin (IL)-6, IL-10 and tumor necrosis factor-α (TNF-α) were measured at the beginning and end of the study. Results: CoQ10 supplementation reduced CGRP and TNF-α significantly (p = 0.011 and p = 0.044, respectively), but there were no significant differences in serum IL-6 and IL-10 between the two groups. Significant increase in serum CoQ10 levels was evident with CoQ10 therapy (P < 0.001). A significant improvement was found in frequency (p = 0.018), severity (p = 0.001) and duration (p = 0.012) of migraine attacks in CoQ10 group compared to placebo. Conclusion: CoQ10 supplementation may decrease CGRP and TNF-α with no favorable effects on IL-6 and IL-10 in patients with migraine.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Inflamação/sangue , Inflamação/tratamento farmacológico , Transtornos de Enxaqueca/tratamento farmacológico , Ubiquinona/análogos & derivados , Administração Oral , Adolescente , Adulto , Biomarcadores/sangue , Método Duplo-Cego , Feminino , Humanos , Inflamação/complicações , Mediadores da Inflamação/sangue , Pessoa de Meia-Idade , Transtornos de Enxaqueca/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Ubiquinona/administração & dosagem , Ubiquinona/sangue , Adulto Jovem
18.
Appl Physiol Nutr Metab ; 44(5): 485-492, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30273493

RESUMO

Simvastatin is a cholesterol-lowering drug that is prescribed to lower the risk of cardiovascular disease following high levels of blood cholesterol. There is a possible risk of new-onset diabetes mellitus with statin treatment but the mechanisms behind are unknown. Coenzyme Q10 (CoQ10) supplementation has been found to improve glucose homeostasis in various patient populations and may increase muscle glucose transporter type 4 content. Our aim was to investigate if 8 weeks of CoQ10 supplementation can improve glucose homeostasis in simvastatin-treated subjects. Thirty-five men and women in treatment with a minimum of 40 mg of simvastatin daily were randomized to receive either 2 × 200 mg/day of CoQ10 supplementation or placebo for 8 weeks. Glucose homeostasis was investigated with fasting blood samples, oral glucose tolerance test (OGTT) and intravenous glucose tolerance test. Insulin sensitivity was assessed with the hyperinsulinemic-euglycemic clamp. Different indices were calculated from fasting samples and OGTT as secondary measures of insulin sensitivity. A muscle biopsy was obtained from the vastus lateralis muscle for muscle protein analyzes. There were no changes in body composition, fasting plasma insulin, fasting plasma glucose, or 3-h glucose with intervention, but glycated hemoglobin decreased with time. Glucose homeostasis measured as the area under the curve for glucose, insulin, and C-peptide during OGTT was unchanged after intervention. Insulin secretory capacity was also unaltered after CoQ10 supplementation. Insulin sensitivity was unchanged but hepatic insulin sensitivity increased. No changes in muscle GLUT4 content was observed after intervention. CoQ10 supplementation does not change muscle GLUT4 content, insulin sensitivity, or secretory capacity, but hepatic insulin sensitivity may improve.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Resistência à Insulina , Sinvastatina/uso terapêutico , Ubiquinona/análogos & derivados , Idoso , Glicemia/análise , Peptídeo C/análise , Feminino , Teste de Tolerância a Glucose , Transportador de Glucose Tipo 4/metabolismo , Hemoglobina A Glicada/análise , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Ubiquinona/administração & dosagem
19.
Nutr Neurosci ; 22(4): 264-272, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28946820

RESUMO

OBJECTIVES: Coenzyme Q10 (CoQ10, ubiquinone) stands among the safest supplements in the elderly to protect against cardiovascular disorders. Noteworthy, CoQ10 deficiency is common in many surviving stroke patients as they are mostly prescribed statins for the secondary prevention of stroke incidence lifelong. Accordingly, the current study aims to experimentally examine whether CoQ10 supplementation in animals receiving atorvastatin may affect acute stroke-induced injury. METHODS: Adult rats underwent transient middle cerebral artery occlusion after atorvastatin pretreatment (5 or 10 mg/ kg/day; po; 30 days) with or without CoQ10 (200 mg/kg/day). After 24 hours ischemic/reperfusion injury, animals were subjected to functional assessments followed by cerebral molecular and histological to detect inflammation, apoptosis and oxidative stress. RESULTS: Animals dosed with 10 mg/kg presented the worst neurological function and brain damage in the acute phase of stroke injury. CoQ10 supplementation efficiently improved functional deficit and cerebral infarction in all stroke animals, particularly those exhibiting statin toxicity. Such benefits were associated with remarkable anti-inflammatory and anti-apoptotic effects, based on the analyzed tumor necrosis factor-α, interleukin-6, Bax/Bcl2 and cleaved caspase 3/9 immunoblots. Importantly, our fluoro-jade staining data indicated CoQ10 may revert the stroke-induced neurodegeneration. No parallel alteration was detected in stroke-induced oxidative stress as determined by malondialdehyde and 8-oxo-2'-deoxyguanosine levels. DISCUSSION: These data suggest that all stroke animals may benefit from CoQ10 administration through modulating inflammatory and degenerative pathways. This study provides empirical evidence for potential advantages of CoQ10 supplementation in atorvastatin-receiving patients which may not shadow its antioxidant properties.


Assuntos
Atorvastatina/administração & dosagem , Isquemia Encefálica/prevenção & controle , Fármacos Neuroprotetores/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Ubiquinona/análogos & derivados , Animais , Apoptose/efeitos dos fármacos , Isquemia Encefálica/complicações , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Encefalite/etiologia , Encefalite/prevenção & controle , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , Resultado do Tratamento , Ubiquinona/administração & dosagem
20.
Neurotox Res ; 35(2): 451-462, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30374909

RESUMO

Phenytoin is one of the most well-known antiepileptic drugs that cause cognitive impairment which is closely related to cAMP response element-binding protein (CREB) brain-derived neurotrophic factor (BDNF) signaling pathway. Moreover, vascular endothelial growth factor (VEGF), an endothelial growth factor, has a documented role in neurogenesis and neuronal survival and cognitive impairment. Therefore, this study aimed to investigate the influence of powerful antioxidants: α-Toc and CoQ10 alone or combined in the preservation of brain tissues and the maintenance of memory formation in phenytoin-induced cognitive impairment in rats. The following behavioral test novel object recognition and elevated plus maze were assessed after 14 days of treatment. Moreover, VEGF, BDNF, TrkB, and CREB gene expression levels in the hippocampus and prefrontal cortex were estimated using RT-PCR. Both α-Toc and CoQ10 alone or combined with phenytoin showed improvement in behavioral tests compared to phenytoin. Mechanistically, α-Toc and/or CoQ10 decreases the VEGF mRNA expression, while increases BDNF-TrKB-CREB mRNA levels in hippocampus and cortex of phenytoin-treated rats. Collectively, α-Toc and/or CoQ10 alleviated the phenytoin-induced cognitive impairment through suppressing oxidative damage. The underlying molecular mechanism of the treating compounds is related to the VEGF and enhancing BDNF-TrkB-CREB signaling pathway. Our study indicated the usefulness α-Toc or CoQ10 as an adjuvant to antiepileptic drugs with an advantage of preventing cognitive impairment and oxidative stress.


Assuntos
Disfunção Cognitiva/metabolismo , Fenitoína/toxicidade , Transdução de Sinais/efeitos dos fármacos , Ubiquinona/análogos & derivados , Fator A de Crescimento do Endotélio Vascular/metabolismo , alfa-Tocoferol/administração & dosagem , Animais , Antioxidantes/administração & dosagem , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Quimioterapia Combinada , Masculino , Ratos , Ratos Wistar , Receptor trkB/metabolismo , Transdução de Sinais/fisiologia , Resultado do Tratamento , Ubiquinona/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
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