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1.
PLoS One ; 15(9): e0239506, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32976523

RESUMO

BACKGROUND: Low carnitine status may underlie the development of insulin resistance and metabolic inflexibility. Intravenous lipid infusion elevates plasma free fatty acid (FFA) concentration and is a model for simulating insulin resistance and metabolic inflexibility in healthy, insulin sensitive volunteers. Here, we hypothesized that co-infusion of L-carnitine may alleviate lipid-induced insulin resistance and metabolic inflexibility. METHODS: In a randomized crossover trial, eight young healthy volunteers underwent hyperinsulinemic-euglycemic clamps (40mU/m2/min) with simultaneous infusion of saline (CON), Intralipid (20%, 90mL/h) (LIPID), or Intralipid (20%, 90mL/h) combined with L-carnitine infusion (28mg/kg) (LIPID+CAR). Ten volunteers were randomized for the intervention arms (CON, LIPID and LIPID+CAR), but two dropped-out during the study. Therefore, eight volunteers participated in all three intervention arms and were included for analysis. RESULTS: L-carnitine infusion elevated plasma free carnitine availability and resulted in a more pronounced increase in plasma acetylcarnitine, short-, medium-, and long-chain acylcarnitines compared to lipid infusion, however no differences in skeletal muscle free carnitine or acetylcarnitine were found. Peripheral insulin sensitivity and metabolic flexibility were blunted upon lipid infusion compared to CON but L-carnitine infusion did not alleviate this. CONCLUSION: Acute L-carnitine infusion could not alleviated lipid-induced insulin resistance and metabolic inflexibility and did not alter skeletal muscle carnitine availability. Possibly, lipid-induced insulin resistance may also have affected carnitine uptake and may have blunted the insulin-induced carnitine storage in muscle. Future studies are needed to investigate this.


Assuntos
Carnitina/administração & dosagem , Ácidos Graxos não Esterificados/sangue , Ácidos Graxos não Esterificados/metabolismo , Resistência à Insulina/fisiologia , Lipídeos/administração & dosagem , Adulto , Carnitina/análogos & derivados , Carnitina/sangue , Estudos Cross-Over , Emulsões/administração & dosagem , Humanos , Bombas de Infusão , Insulina/sangue , Insulina/metabolismo , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Fosfolipídeos/administração & dosagem , Óleo de Soja/administração & dosagem , Adulto Jovem
2.
PLoS One ; 15(8): e0237097, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32810864

RESUMO

Neurofibromatosis type 1 (NF1) is a genetic disorder that affects a range of tissue systems, however the associated muscle weakness and fatigability can have a profound impact on quality of life. Prior studies using the limb-specific Nf1 knockout mouse (Nf1Prx1-/-) revealed an accumulation of intramyocellular lipid (IMCL) that could be rescued by a diet supplemented with L-carnitine and enriched for medium-chain fatty acids (MCFAs). In this study we used the Nf1Prx1-/- mouse to model a range of dietary interventions designed to reduce IMCL accumulation, and analyze using other modalities including in situ muscle physiology and lipid mass spectrometry. Histological IMCL accumulation was significantly reduced by a range of treatments including L-carnitine and high MCFAs alone. A low-fat diet did not affect IMCL, but did provide improvements to muscle strength. Supplementation yielded rapid improvements in IMCL within 4 weeks, but were lost once treatment was discontinued. In situ muscle measurements were highly variable in Nf1Prx1-/- mice, attributable to the severe phenotype present in this model, with fusion of the hips and an overall small hind limb muscle size. Lipidome analysis enabled segregation of the normal and modified chow diets, and fatty acid data suggested increased muscle lipolysis with the intervention. Acylcarnitines were also affected, suggestive of a mitochondrial fatty acid oxidation disorder. These data support the theory that NF1 is a lipid storage disease that can be treated by dietary intervention, and encourages future human trials.


Assuntos
Metabolismo dos Lipídeos , Força Muscular , Músculo Esquelético/metabolismo , Neurofibromatose 1/dietoterapia , Animais , Carnitina/administração & dosagem , Carnitina/uso terapêutico , Suplementos Nutricionais , Ácidos Graxos/administração & dosagem , Ácidos Graxos/uso terapêutico , Feminino , Camundongos , Músculo Esquelético/fisiopatologia , Neurofibromatose 1/genética , Neurofibromina 1/genética
3.
Anim Sci J ; 91(1): e13390, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32468653

RESUMO

This study was carried out to evaluate the nutritional effects of rice feeding and carnitine addition to a diet for broiler chicks. Thirty-six male 10-day-old broiler chicks were assigned to one of the following four treatment groups: corn-based diet (corn group), rice-based diet (rice group), and each diet with added carnitine (100 ppm). The experimental period was 2 weeks. Rice feeding resulted in significantly higher growth performance (body weight gain and feed efficiency) compared to corn feeding. Carnitine addition also resulted in higher growth performance. Breast muscle and thigh muscle weight (g) were significantly higher in broiler chicks fed rice and those fed diets with added carnitine. Liver mRNA expression of IGF-I was significantly higher in broiler chicks fed rice compared to those fed corn. There was no significant difference in mRNA expression of muscle atrogin-1 or liver CPT-I between broiler chicks fed rice and those fed corn, not between broilers chicks fed diets containing carnitine or not. Overall, these results show that rice feeding and carnitine addition improve the growth performance of broiler chicks by increasing mRNA expression of liver IGF-I. In addition, carnitine action is not affected by different cereals (corn and rice).


Assuntos
Ração Animal , Fenômenos Fisiológicos da Nutrição Animal/genética , Fenômenos Fisiológicos da Nutrição Animal/fisiologia , Carnitina/administração & dosagem , Galinhas/crescimento & desenvolvimento , Galinhas/genética , Galinhas/metabolismo , Dieta/veterinária , Suplementos Nutricionais , Expressão Gênica , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Oryza , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Animais , Fígado/metabolismo , Masculino , Zea mays
4.
Arch Med Res ; 51(1): 82-94, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32113058

RESUMO

BACKGROUND AND AIM: Possible Hepato-protective effects of L-carnitine have been reported in previous studies. Present study was conducted to systematically review the efficacy of L-carnitine supplementation on liver enzymes. METHODS: The following databases were searched up to December 2018: PubMed, Scopus, ISI Web of Science, and the Cochrane library. Only randomized controlled trials (RCTs) evaluating the effects of L-carnitine supplementation on liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) were included. Pooled effect size measured using random effect model (Dersimonian-Liard). RESULTS: A total of 16 studies (including 1025 participants) were included in the present meta-analysis. Pooled analysis indicated that L-carnitine supplementation significantly decreased ALT (weighted mean difference (WMD): -10.729 IU/L, 95% CI: -13.787, -7.672, p <0.001; I2 = 95.9%), AST (WMD: -7.149 IU/L, 95% CI: -9.202, -5.096, p <0.001; I2 = 93.5%) and GGT (WMD: -7.395: IU/L, 95% CI: -9.171, -5.619, p <0.001; I2 = 80.1%). Subgroup analysis revealed that effect of L-carnitine supplementation on liver enzymes was not significant in normal weight and healthy subjects. Baseline BMI and health status were the potential source of heterogeneity. CONCLUSION: L-carnitine supplementation showed beneficial hepato-protective effects on circulating liver enzymes.


Assuntos
Carnitina/farmacologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Alanina Transaminase/efeitos dos fármacos , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/efeitos dos fármacos , Aspartato Aminotransferases/metabolismo , Carnitina/administração & dosagem , Citoproteção/efeitos dos fármacos , Suplementos Nutricionais , Humanos , Fígado/metabolismo , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/farmacologia , gama-Glutamiltransferase/efeitos dos fármacos , gama-Glutamiltransferase/metabolismo
5.
PLoS One ; 15(3): e0229772, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32126131

RESUMO

BACKGROUND: Fatigue is a common adverse event during lenvatinib treatment in patients with hepatocellular carcinoma. One mechanism contributing to development of fatigue might involve abnormal adenosine triphosphate synthesis that is caused by carnitine deficiency. To address this possibility, we examined the relationship between carnitine levels and fatigue during lenvatinib treatment. METHODS: This prospective study evaluated 20 patients with hepatocellular carcinoma who underwent lenvatinib treatment. Both blood and urine samples were collected from the patients before starting lenvatinib therapy (day 0), and on days 3, 7, 14, and 28 thereafter. Plasma and urine concentrations of free and acyl carnitine (AC) were assessed at each time point. The changes in daily fatigue were evaluated using the Brief Fatigue Inventory (BFI). RESULTS: Plasma levels of free carnitine (FC) at days 3 and 7 were significantly higher compared with baseline (p = 0.005, p = 0.005, respectively). The urine FC level at day 3 was significantly higher compared with baseline (p = 0.030) and that of day 7 tended to be higher compared with baseline (p = 0.057). The plasma AC concentration at days 14 and 28 was significantly higher compared with that of baseline (p = 0.002, p = 0.005, respectively). The plasma AC-to-FC (AC/FC) ratio on days 14 and 28 was significantly higher compared with baseline (p = 0.001, p = 0.003, respectively). There were significant correlations between the plasma AC/FC ratio and the change in the BFI score at days 14 and 28 (r = 0.461, p = 0.041; r = 0.770, p = 0.002, respectively). CONCLUSIONS: Longitudinal assessments of carnitine and fatigue in patients with hepatocellular carcinoma suggest that lenvatinib affects the carnitine system in patients undergoing lenvatinib therapy and that carnitine insufficiency increases fatigue. The occurrence of carnitine insufficiency may be a common cause of fatigue during the treatment.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Cardiomiopatias/induzido quimicamente , Carnitina/deficiência , Fadiga/etiologia , Hiperamonemia/induzido quimicamente , Neoplasias Hepáticas/tratamento farmacológico , Doenças Musculares/induzido quimicamente , Compostos de Fenilureia/efeitos adversos , Quinolinas/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/urina , Cardiomiopatias/sangue , Cardiomiopatias/complicações , Cardiomiopatias/dietoterapia , Carnitina/administração & dosagem , Carnitina/sangue , Carnitina/urina , Suplementos Nutricionais , Fadiga/sangue , Fadiga/diagnóstico , Fadiga/prevenção & controle , Feminino , Humanos , Hiperamonemia/sangue , Hiperamonemia/complicações , Hiperamonemia/dietoterapia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/urina , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doenças Musculares/sangue , Doenças Musculares/complicações , Doenças Musculares/dietoterapia , Estudos Prospectivos , Resultado do Tratamento
6.
Molecules ; 25(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31906370

RESUMO

l-Carnitine is an amino acid derivative widely known for its involvement in the transport of long-chain fatty acids into the mitochondrial matrix, where fatty acid oxidation occurs. Moreover, l-Carnitine protects the cell from acyl-CoA accretion through the generation of acylcarnitines. Circulating carnitine is mainly supplied by animal-based food products and to a lesser extent by endogenous biosynthesis in the liver and kidney. Human muscle contains high amounts of carnitine but it depends on the uptake of this compound from the bloodstream, due to muscle inability to synthesize carnitine. Mitochondrial fatty acid oxidation represents an important energy source for muscle metabolism particularly during physical exercise. However, especially during high-intensity exercise, this process seems to be limited by the mitochondrial availability of free l-carnitine. Hence, fatty acid oxidation rapidly declines, increasing exercise intensity from moderate to high. Considering the important role of fatty acids in muscle bioenergetics, and the limiting effect of free carnitine in fatty acid oxidation during endurance exercise, l-carnitine supplementation has been hypothesized to improve exercise performance. So far, the question of the role of l-carnitine supplementation on muscle performance has not definitively been clarified. Differences in exercise intensity, training or conditioning of the subjects, amount of l-carnitine administered, route and timing of administration relative to the exercise led to different experimental results. In this review, we will describe the role of l-carnitine in muscle energetics and the main causes that led to conflicting data on the use of l-carnitine as a supplement.


Assuntos
Carnitina/análogos & derivados , Carnitina/metabolismo , Metabolismo Energético/efeitos dos fármacos , Ácidos Graxos/metabolismo , Mitocôndrias/metabolismo , Músculo Esquelético/metabolismo , Carnitina/administração & dosagem , Carnitina/biossíntese , Carnitina/química , Carnitina/farmacologia , Carnitina O-Palmitoiltransferase/metabolismo , Suplementos Nutricionais/efeitos adversos , Exercício Físico/fisiologia , Humanos , Metilaminas/metabolismo , Músculo Esquelético/efeitos dos fármacos , Oxirredução
7.
Complement Ther Med ; 48: 102273, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31987257

RESUMO

OBJECTIVE: The beneficial effects of carnitine supplementation on nonalcoholic fatty liver disease are unclear. We conducted a systematic review and meta-analysis to evaluate the effects of carnitine supplementation on liver function, lipid profile, body mass index, body weight, and homeostasis model assessment of insulin resistance in patients with nonalcoholic fatty liver disease. METHODS: A comprehensive search of PubMed, Web of Science, Scopus, Cochrane Library, and Google Scholar databases were performed. Only randomized placebo-controlled human studies that examined the effects of carnitine supplementation on liver function, lipid profile, body mass index, body weight, and homeostasis model assessment of insulin resistance up to September 2019 were included. Fixed effects or random-effects models were applied to compute the pooled effect size. Heterogeneity assessments were performed using Cochran's Q test and I-squared statistics. The quality of the studies was assessed using the Jaded scale. RESULTS: A total of 5 articles were selected, including 334 individuals (167 in control and 167 in intervention groups). The results demonstrated that carnitine supplementation significantly reduced homeostasis model assessment of insulin resistance (HOMA-IR) (WMD: -0.91; 95 % CI: -1.11, -0.72; p < 0.001, I2 = 0.0 %) and the levels of aspartate aminotransferase (AST) (WMD: -16.62; 95 % CI: -28.11, -5.14; IU/l; p = 0.005, I2 = 93.5 %), alanine aminotransferase (ALT) (WMD: -33.39; 95 % CI: -45.13, -21.66; IU/l; p < 0.001, I2 = 93.4 %), and triglycerides (TG) (WMD: -22.13; 95 % CI: -38.91, -5.34; mg/dl; p = 0.01; I2 = 0.0 %). However, the results of the pooled effect size did not show any significant effect of carnitine supplementation on body mass index (BMI) (WMD: 0.07; 95 % CI: -0.15, 0.29; p = 0.55; I2 = 0.0 %), body weight (WMD: -0.28; 95 % CI: -2.23, 1.68; p = 0.78; I2 = 45.7 %), the levels of gamma-glutamyl transferase (γGT) (WMD: -11.31; 95 % CI: -24.35, 1.73; IU/l; p = 0.09, I2 = 61.1 %), cholesterol (WMD: -13.58; 95 % CI: -46.77, 19.60; mg/dl; p = 0.42; I2 = 94.9 %), high-density lipoprotein-cholesterol (HDL-C) (WMD: 1.36; 95 % CI: -0.96, 3.68; mg/dl; p = 0.25; I2 = 64.7 %), and low density lipoprotein-cholesterol (LDL-C) (WMD: -14.85; 95 % CI: -45.43, 15.73; mg/dl; p = 0.34; I2 = 96.4 %). CONCLUSIONS: This analysis shows that carnitine supplementation for patients with nonalcoholic fatty liver disease demonstrates a reduction in AST, ALT, TG levels and HOMA-IR. However, no significant effect of carnitine supplementation was observed on BMI, body weight, the levels of γGT, TC, HDL-cholesterol and LDL-cholesterol.


Assuntos
Carnitina/administração & dosagem , Suplementos Nutricionais , Hepatopatia Gordurosa não Alcoólica/terapia , Índice de Massa Corporal , Peso Corporal , Humanos , Resistência à Insulina , Lipídeos/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(12): 1167-1170, 2019 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-31813139

RESUMO

OBJECTIVE: To study the prevalence, clinical and genetic characteristics of primary carnitine deficiency (PCD). METHODS: From January 2013 to December 2017, 720 667 newborns and their mothers were tested for PCD by tandem mass spectrometry. Potential mutations of carnitine transporter gene SLC22A5 among suspected PCD patients were analyzed. Dietary guidance and L-carnitine supplementation were provided to the parents. Growth and intelligence development were surveyed during follow-up. RESULTS: In total 21 neonates and 6 mothers were diagnosed with PCD, which yielded an incidence of 1 in 34 317. Eighteen SLC22A5 mutations were detected, which included 4 novel mutations, namely c.1484T>C, c.394-1G>T, c.431T>C and c.265-266insGGCTCGCCACC. Eighteen patients were found to carry compound heterozygous mutations and 3 have carried homozygous SLC22A5 mutations. Three mothers carried compound heterozygous mutations and 2 carried homozygous mutations. Common mutations included c.1400C>G (42.3%), c.760C>T (11.5%) and c.51C>G (7.7%). During the 8-42 month follow-up, neonates with PCD showed no clinical symptoms but normal growth. Blood level of free carnitine was raised in all mothers after the treatment. CONCLUSION: The incidence of neonatal PCD in Henan is 1 in 34 317, with the most common mutation being c.1400C>G. Above finding has enriched the spectrum of SLC22A5 gene mutations.


Assuntos
Cardiomiopatias/genética , Carnitina/deficiência , Hiperamonemia/genética , Doenças Musculares/genética , Membro 5 da Família 22 de Carreadores de Soluto/genética , Cardiomiopatias/epidemiologia , Carnitina/administração & dosagem , Carnitina/genética , China , Feminino , Humanos , Hiperamonemia/epidemiologia , Recém-Nascido , Doenças Musculares/epidemiologia , Mutação , Triagem Neonatal
9.
Vopr Pitan ; 88(4): 25-33, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31722138

RESUMO

The aim of the study was to assess the impact of L-carnitine and phosphatidylcholine containing products on the production of the proatherogenic metabolite TMAO and gut microbiome changes in patients with coronary artery disease (CAD). Material and methods. The study consisted of 2 parts. In the first part, a comparison was made between the diet of patients with CAD (n=29) and healthy volunteers (n=30) over the age of 50 with respect to the frequency of intake of L-carnitine and phosphatidylcholine containing products. All participants underwent blood sampling and stool tests to assess the concentration of TMAO and the composition of fecal microflora. The second part of the study was dedicated to assessing the correlation between TMAO blood concentration in patients with CAD (n=89) and the frequency of intake of L-carnitine and phosphatidylcholine containing products. Results and discussion. Patients with CAD comparing to healthy people among the predecessor products of TMAO consumed red meat, dairy products more often, eggs and fish less often. TMAO concentration in patients with CAD was higher than in healthy volunteers (1036.4±748.2 vs 376.5±147.9 ng/ml, p=0.0001). Analysis of fecal microflora in patients with CAD revealed an increase number of bacteria from Verrucomicrobiaceae family (p<0.05) and Enterobacteriaceae family (p<0.05), of the Escherichia/Shigella genera (p<0.05), there was a trend to increased number of Ruminococcus (р=0.065), Clostridium XlV (b) genera (р=0.10). Correlation between TMAO concentration and frequency of red meat, eggs, and dairy products consumption was estimated in patients with CAD (r>0.525, р<0.05). Conclusion. Patients with CAD consume more precursors of TMAO, have higher blood TMAO concentrations compared to healthy volunteers. Fecal microflora of patients with CAD contains a greater number of gut bacteria related to trimethylamine producers compared to healthy volunteers. Reducing the number of L-carnitine and phosphatidylcholine containing products in the diet of patients with CAD may affect the decrease in the proatherogenic metabolite TMAO concentration.


Assuntos
Bactérias , Carnitina/administração & dosagem , Doença da Artéria Coronariana , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/microbiologia , Metilaminas/metabolismo , Fosfatidilcolinas/administração & dosagem , Idoso , Bactérias/classificação , Bactérias/metabolismo , Doença da Artéria Coronariana/dietoterapia , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
Molecules ; 24(23)2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31766743

RESUMO

Carnitine is an amino acid derivative, which plays several important roles in human physiology, in the central nervous system, and for mitochondrial metabolism, in particular. Altered carnitine metabolic routes have been associated with a subgroup of patients with autism spectrum disorders (ASD) and could add to the pathophysiology associated with these disorders. We review the current evidence about the clinical effects of carnitine administration in ASD in both non-syndromic forms and ASD associated with genetic disorders. Two randomized clinical trials and one open-label prospective trial suggest that carnitine administration could be useful for treating symptoms in non-syndromic ASD. The effect of carnitine administration in ASD associated with genetic disorders is not conclusive because of a lack of clinical trials and objectives in ASD evaluation, but beneficial effects have also been reported for other comorbid disorders, such as intellectual disability and muscular strength. Side effects observed with a dose of 200 mg/kg/day consisted of gastro-intestinal symptoms and a strong, heavy skin odor. Doses of about 50-100 mg/kg/day are generally well tolerated. Further clinical trials with the identification of the subgroup of ASD patients that would benefit from carnitine administration are warranted.


Assuntos
Transtorno do Espectro Autista/tratamento farmacológico , Carnitina/administração & dosagem , Transtorno do Espectro Autista/genética , Carnitina/efeitos adversos , Comorbidade , Relação Dose-Resposta a Droga , Predisposição Genética para Doença , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
11.
An Acad Bras Cienc ; 91(4): e20180907, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31644644

RESUMO

A total number of 300 (225 ducks and 75 drakes) Sudani ducks, 28-wk-old were divided into five groups to investigate the effects of dietary L-carnitine (LC) supplementation on productive, hatching and physiological performance as well as nutrients digestibility coefficients. The results indicated that the productive performance and Semen quality parameters (ejaculate volume, sperms concentration and advanced motility) were significantly improved by LC supplementation (150-450 mg /kg diet) as compared to the control. Hatchability of fertile eggs (%) was significantly improved, while total embryonic mortality was significantly decreased by supplementing 300 and 450 mg LC/kg diet. Supplementing different dietary LC levels resulted in significantly high values of hemoglobin, red and white blood cells count and lymphocyte (L) cells percentage, while it decreased heterophils (H) cells and H/L ratio. Serum albumin, total cholesterol and AST enzyme values were significantly low in ducks fed diets supplemented with LC. Serum triglycerides were significantly the lowest by feeding 300 and 450 mg LC/kg diet. Nutrients digestibility coefficients were significantly improved in drakes fed diet supplemented with 450 mg LC/kg diet. Conclusively, dietary LC supplementation at 300 or 450 mg/kg for duck breeders in summer could improve productive, hatching and physiological performance and nutrients digestibility coefficients.


Assuntos
Ração Animal , Carnitina/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais , Patos/crescimento & desenvolvimento , Fenômenos Fisiológicos da Nutrição Animal , Animais , Análise Química do Sangue/veterinária , Digestão/fisiologia , Patos/fisiologia , Feminino , Masculino , Estações do Ano , Análise do Sêmen
12.
Drug Metab Pers Ther ; 34(3)2019 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-31603853

RESUMO

Background Cytochrome P450s (CYPs, EC 1.14.14.1) are the main enzymes of drug metabolism. The functional significance of CYPs also includes the metabolism of foreign chemicals and endogenic biologically active compounds. The CYP3A4 isoform contributes to the metabolism of about half of all marketed medicinal preparations. The aim of this study was to investigate the effects of two biologically active compounds: 2-aminoethane-sulfonic acid (taurine) and 3-hydroxy-4-trimethylaminobutyrate (L-carnitine) on urinary 6ß-hydroxycortisol/cortisol (6ß-OHC/cortisol) metabolic ratio as a biomarker of the CYP3A4 activity of healthy volunteers. Taurine is used for the treatment of chronic heart failure and liver disease. Cardiologists, nephrologists, neurologists, gerontologists in addition to the main etiopathogenetic therapies, use L-carnitine. The quantification of the 6ß-OHC/cortisol metabolic ratio as a biomarker of CYP3A4 activity in human urine was used for the assessment of CYP3A4 catalytic activity as a non-invasive test. Methods The study included 18 healthy male volunteers (aged from 18 to 35 years old). The volunteers took taurine in a dose of 500 mg twice a day or L-carnitine in a dose of 2.5 mL 3 times a day for 14 consecutive days. The test drug was given 20 min before meals. The collection of urine samples was performed before and after 3, 7, 10, and 14 days after taurine intake. The metabolic ratio of 6ß-OHC/cortisol in morning spot urine samples was studied by the liquid chromatography/mass spectroscopy (LC/MS) method. Results The ratio of 6-6ß-OHC/cortisol was used as a biomarker to study the taurine and L-carnitine influence on CYP3A4 metabolism of cortisol. The ratio of urinary 6ß-OCH/cortisol in the morning urine samples of volunteers before the beginning of taurine therapy (baseline ratio) was 2.71 ± 0.2. Seven days after the administration of taurine in a dose of 500 mg twice a day, the 6ß-OCH/cortisol ratio was 3.3 ± 0.2, which indicated the increased catalytic activity of CYP3A4 towards cortisol. As for the L-carnitine supplementation, analysis of the 6ß-OCH/cortisol ratio in the urine for 14 days did not show any significant changes in this baseline ratio, indicating the lack of L-carnitine influence on the catalytic activity of CYP3A4 to cortisol. Conclusions The results obtained demonstrated the influence of taurine on 6ß-OCH/cortisol metabolic ratio as a biomarker of CYP3A4 catalytic activity to cortisol. L-carnitine did not affect the activity of CYP3A4. The lack of a clinically meaningful effect of L-carnitine was established.


Assuntos
Carnitina/metabolismo , Hidrocortisona/análogos & derivados , Hidrocortisona/metabolismo , Hidrocortisona/urina , Taurina/metabolismo , Administração Oral , Adolescente , Adulto , Biomarcadores/metabolismo , Biomarcadores/urina , Carnitina/administração & dosagem , Cromatografia Líquida , Citocromo P-450 CYP3A/metabolismo , Voluntários Saudáveis , Humanos , Masculino , Espectrometria de Massas , Taurina/administração & dosagem , Adulto Jovem
13.
Food Chem Toxicol ; 134: 110851, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31568849

RESUMO

This study investigated the effects of L-carnitine supplementation on carnitine levels, oxidative stress and apoptotic markers in the stomach, kidney, liver and testis tissues in adult rats. Rats were randomized to control and L-carnitine supplemented (LCAR) groups. Control group received distilled water for 7 months by intragastric gavage and the LCAR group was given 50 mg/kg/day L-carnitine via intragastric intubation for the same period. L-carnitine concentrations and caspase-3 activity were measured by fluorometric methods while cleaved caspase-3 was determined by Western blot analysis. Bcl-2 associated X protein (Bax) and B-cell lymphoma/leukemia-2 (Bcl-2) were quantified by enzyme immunoassay and Western blot analysis. Oxygen/nitrogen species (ROS/RNS) and total antioxidant capacity (TAC) were analyzed by colorimetric assay. Tissue L-carnitine concentrations were significantly increased in the LCAR group compared to controls. Anti-apoptotic Bcl-2 levels were significantly increased while pro-apoptotic Bax was significantly decreased in LCAR group rats compared to controls. Tissue caspase-3 was significantly alleviated in the LCAR group compared to controls. L-carnitine supplementation increased TAC and decreased ROS/RNS generation in the kidney, liver, stomach and testis tissues compared to controls. Obtained data suggests that L-carnitine supplementation can potentially be used to lessen both oxidative and apoptotic progression in peripheral organs.


Assuntos
Apoptose/efeitos dos fármacos , Carnitina/administração & dosagem , Carnitina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Carnitina/farmacologia , Masculino , Ratos , Ratos Wistar
14.
Fish Shellfish Immunol ; 93: 1100-1110, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31422179

RESUMO

Nrf2/Keap1 pathway is associated with oxidative stress. l-carnitine is currently under preclinical evaluation as a antioxidant, but the use of l-carnitine in aquaculture has been poorly evaluated and so far no mechanism has been demonstrated. Here, we explored the effects of l-carnitine in vitro and in vivo and discussed the possible molecular mechanisms involved. Firstly, Nrf2-siRNA significantly knocked down the mRNA level of Nrf2 in FHM cells. Thus, the activities of antioxidant enzymes (T-SOD, CAT, GSH-PX) and the level of antioxidant substance (GSH) and the level of MDA showed that Nrf2-siRNA pretreatment weakened the protective effect of l-carnitine. Moreover, the mRNA levels of Keap1, Nrf2, Maf and HO-1 indicated that l-carnitine regulated Nrf2/Keap1 activation. Furthermore, oxidized fish oil remarkably suppressed growth in Rhynchocypris lagowski Dybowski, and the lower antioxidant capacity was also observed in liver. According to the results of immune related indexes (the levels of IL-1ß, TNF-α, LZM, AKP) in serum and the mRNA levels of immune related genes (NF-κB, IL-1ß, TNF-α, IL-8, IL-10 and TGF-ß) in liver, oxidized fish oil also induced inflammatory response in fish. Also, l-carnitine supplementation can relieve this bad condition. In conclusion, l-carnitine regulated Nrf2/Keap1 activation in vitro and in vivo and protected oxidized fish oil-induced inflammation response by inhibiting the NF-κB signaling pathway in Rhynchocypris lagowski Dybowski.


Assuntos
Carnitina/metabolismo , Cyprinidae/imunologia , Doenças dos Peixes/imunologia , Proteínas de Peixes/metabolismo , Substâncias Protetoras/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Carnitina/administração & dosagem , Proteínas de Transporte/metabolismo , Linhagem Celular , Cyprinidae/genética , Cyprinidae/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Doenças dos Peixes/tratamento farmacológico , Óleos de Peixe/farmacologia , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/veterinária , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Oxirredução , Estresse Oxidativo , Substâncias Protetoras/administração & dosagem , Distribuição Aleatória
15.
Dermatol Ther ; 32(5): e13049, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31369185

RESUMO

Pemphigus vulgaris (PV) is a severe, bullous, autoimmune disease of the skin and mucous membranes. Corticosteroids are usually the main core treatment for controlling PV, which could lead to several side effects such as insulin resistance, osteoporosis, and cardiovascular disorders. The aim of this study is to evaluate the protective effects of l-carnitine (LC) supplementation in PV patients under corticosteroid treatment. In this randomized, double-blind, placebo-controlled clinical trial, 48 patients with PV were divided randomly into two groups to receive 2 g LC (n = 24) or a placebo (n = 24) for 8 weeks, respectively. Serum levels of osteopontin (OPN), bone morphogenic protein 4 (BMP4), cystatin C, systolic and diastolic blood pressure, 25 hydroxyvitamin D3, and LC were evaluated at the beginning and at the end of the study. LC supplementation demonstrated a significant increase in serum carnitine (p < .001). In addition, at the end of the trial, LC supplementation significantly decreased serum BMP4 (p = .003), OPN (p = .03), and cystatin C (p = .001) levels. There was no significant effect on blood pressure in comparison with the placebo. During study, no harmful side effects were reported by patients. These findings indicate that LC supplementation significantly leads to favorable changes in OPN, BMP4, and cystatin C in PV patients under corticosteroid therapy. However, further investigations are required to confirm these results.


Assuntos
Corticosteroides/uso terapêutico , Carnitina/administração & dosagem , Suplementos Nutricionais , Pênfigo/diagnóstico , Pênfigo/tratamento farmacológico , Corticosteroides/efeitos adversos , Adulto , Biomarcadores/sangue , Remodelação Óssea/fisiologia , Carnitina/sangue , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Prognóstico , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Resultado do Tratamento
17.
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
18.
Rinsho Shinkeigaku ; 59(5): 258-263, 2019 May 28.
Artigo em Japonês | MEDLINE | ID: mdl-31061301

RESUMO

A 79-year-old female was diagnosed with epilepsy because she experienced loss of consciousness twice in January and February and then had a seizure in June 2016. She was treated with 800 mg sodium valproate (sustained release). After 3 days, she experienced loss of appetite, and more than 3 days later, disturbance of consciousness. Serum valproic acid (VPA) concentration was 128.3 µg/ml and serum ammonia was 404 µmol/l. Cerebral edema and status epilepticus occurred. Severe neurological dysfunction remained, even after treatment with continuous hemodiafiltration and levocarnitine. VPA is widely used for the treatment of generalized epilepsy. VPA-induced hyperammonemic encephalopathy is a rare but serious adverse event of VPA. Thus, we must pay attention to serum ammonia levels when using VPA, even VPA monotherapy.


Assuntos
Anticonvulsivantes/efeitos adversos , Cardiomiopatias/induzido quimicamente , Carnitina/deficiência , Epilepsia Generalizada/tratamento farmacológico , Hiperamonemia/induzido quimicamente , Doenças Musculares/induzido quimicamente , Síndromes Neurotóxicas/etiologia , Ácido Valproico/efeitos adversos , Idoso , Amônia/sangue , Anticonvulsivantes/administração & dosagem , Biomarcadores/sangue , Carnitina/administração & dosagem , Transtornos da Consciência/etiologia , Feminino , Humanos , Hiperamonemia/sangue , Hiperamonemia/diagnóstico , Estado Epiléptico/etiologia , Ácido Valproico/administração & dosagem
19.
J Anim Physiol Anim Nutr (Berl) ; 103(4): 1207-1217, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30994244

RESUMO

This study examined the influence of adding different amounts of maternal dietary l-carnitine and two fat types on fatty acid (FA) composition and the expression of lipid metabolism-related genes in piglets. The experiment was designed as a 2 × 2 factorial with two fat types (3.5% soyabean oil, SO, and 3.5% fish oil, FO) and two levels of l-carnitine (0 and 100 mg/kg) added to the sows' diets. A higher proportion of n-3 polyunsaturated fatty acids (PUFA) and a lower ratio of n-6/n-3 PUFA in sow milk and piglet tissues were observed in the FO groups than in the SO groups. Adding l-carnitine increased the proportion of C16:1 in sow milk and decreased n-3 PUFA in piglet subcutaneous fat. Hepatic peroxisome proliferator-activated receptor α (PPAR-α) was more abundantly expressed in piglets from the FO groups than from the SO groups (p < 0.05), whereas stearoyl-CoA-desaturase (SCD), sterol regulatory element binding protein-1 (SREBP1) and ∆6-desaturase (D6D) genes were less expressed in the FO groups compared with piglets from the SO groups. The expression of fatty acid synthase (FAS) genes was decreased in the SO groups with l-carnitine compared to that of the other dietary treatments. No differences among dietary treatments were observed with regard to the expression of acetyl-CoA carboxylase (ACC). In conclusion, FO and l-carnitine supplementation in sows affect FA composition and hepatic gene expression in piglets.


Assuntos
Ração Animal/análise , Carnitina/farmacologia , Dieta/veterinária , Gorduras na Dieta/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Suínos , Fenômenos Fisiológicos da Nutrição Animal , Animais , Carnitina/administração & dosagem , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Lactação , Fenômenos Fisiológicos da Nutrição Materna , Leite/química , Gravidez
20.
Poult Sci ; 98(9): 4172-4181, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31001634

RESUMO

Precise natural anti-oxidative compounds have facilitated the research of infertile gametes and the development of novel bio-therapeutics, especially the molecules that are based on the reduction of oxidative stress, such as L-carnitine (LC). In addition to, the defect in the functioning of sperm mitochondrial and the decreasing seminal antioxidant ability due to aging, its essential role in permitting the mitochondrial import and oxidation of long chain fatty acids is worthy. Therefore, current study was designed to investigate the effects of dietary LC on semen quality, seminal antioxidant activity, and their implications for the fertility in aged cocks for 12 wk. Supplementation of the feed with two different doses of LC (50 and 150 mg/kg body weight/day) for 12 wk showed significantly increased in the reproductive activity of cock, in comparison to the control group. Seminal analysis showed that supplementation of LC significantly increased (P < 0.05) the sperm motility, concentration, livability, semen quality factor, seminal malondialdehyde concentration, catalase, and glutathione peroxidase activities. In addition, addition of LC significantly increased (P < 0.05) the plasma concentration of testosterone and prostaglandin E2 but posed no significant effect on the concentration of follicle-stimulating hormone. Furthermore, the findings of artificial insemination showed significant increased (P < 0.05) in the percentage of fertility in LC groups, while the percentage hatchability and mortality remained unchanged. Immunohistochemistry analysis revealed that LC significantly increased (P < 0.05) the testicular immunopositivity of MT1 and MT2. Moreover, the administration of LC to the aged cocks enhanced (P < 0.05) GnRH1 and GnRHR mRNA levels when compared with untreated cocks. The results of the present study suggest that LC treatment of aged cocks increases the seminal antioxidant enzymes and sexual hormones levels, which may improve the semen quality by increasing the expression of GnRH1 and melatonin receptors (MT1 and MT2) activities. Collectively, LC could be a suitable feed supplementation to increase reproductive activities through enhancing semen quality in aging cocks.


Assuntos
Antioxidantes/metabolismo , Proteínas Aviárias/genética , Carnitina/metabolismo , Galinhas/fisiologia , Expressão Gênica/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Envelhecimento/efeitos dos fármacos , Ração Animal/análise , Animais , Antioxidantes/administração & dosagem , Proteínas Aviárias/metabolismo , Carnitina/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Hormônio Liberador de Gonadotropina/genética , Hormônio Liberador de Gonadotropina/metabolismo , Masculino , Receptor MT1 de Melatonina/genética , Receptor MT1 de Melatonina/metabolismo , Receptor MT2 de Melatonina/genética , Receptor MT2 de Melatonina/metabolismo , Receptores LHRH/genética , Receptores LHRH/metabolismo , Análise do Sêmen/veterinária , Espermatozoides/fisiologia , Testículo/metabolismo
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