RESUMO
The objective of this exploratory study was to assess the changes on lipidome and metabolome profiling of Longissimus lumborum bull muscle with different ultimate pH (pHu) and aging periods. The bull muscles classified as normal, intermediate, or high pHu were collected from a Brazilian commercial slaughterhouse, cut into steaks, individually vacuum-packaged, and aged for 3 days (3-d) or 21 days (21-d) at 2 °C. Muscle extracts were analyzed for the profiles of both lipids, by mass spectrometry (via direct flow-injection), and metabolites, by nuclear magnetic resonance, with downstream multivariate data analysis. As major results, pairwise comparisons identified C12:0 and C14:0 acylcarnitines as potential biomarkers of the intermediate pHu-muscle, which are related to lipid catabolism for alternative energy metabolism and indicate less protein breakage postmortem. Interestingly, the concentration of arginine at early postmortem aging (3-d) may influence the previously reported improved tenderness in normal and high pHu-muscles. Moreover, upregulation of fumarate, formate, and acetate with increased pHu muscle at 21-d aging indicate more intense tricarboxylic acid cycle, amino acid degradation, and pyruvate oxidation by reactive oxygen species, respectively. These three compounds (fumarate, formate, and acetate) discriminated statistically the muscle with high pHu at 21-d aging. The normal pHu-muscle showed higher concentrations of glycogenolysis and glycolysis metabolites, including glucose, mannose, and pyruvate. Hence, our results enhance knowledge of postmortem biochemical changes of beef within different pHu groups aged up to 21 days, which is essential to understand the mechanisms underpinning bull meat quality changes.
Assuntos
Metaboloma , Músculo Esquelético , Carne Vermelha , Animais , Bovinos , Carne Vermelha/análise , Músculo Esquelético/química , Músculo Esquelético/metabolismo , Concentração de Íons de Hidrogênio , Masculino , Lipidômica/métodos , Mudanças Depois da Morte , Brasil , Manipulação de Alimentos/métodos , Formiatos , Carnitina/análogos & derivados , Carnitina/metabolismo , Carnitina/análiseRESUMO
INTRODUCTION: Recent studies have implicated acetyl-L-carnitine as well as other acylcarnitines in depression. To our knowledge, no untargeted metabolomics studies have been conducted among US mainland Puerto Ricans. OBJECTIVES: We conducted untargeted metabolomic profiling on plasma from 736 participants of the Boston Puerto Rican Health Study. METHODS: Using Weighted Gene Co-expression Network Analysis, we identified metabolite modules associated with depressive symptomatology, assessed via the Center for Epidemiologic Studies Depression scale. We identified metabolites contributing to these modules and assessed the relationship between these metabolites and depressive symptomatology. RESULTS: 621 annotated metabolites clustered into eight metabolite modules, of which one, the acylcarnitine module, was significantly inversely associated with depressive symptomatology (ß = - 27.7 (95% CI (- 54.5-0.8); p = 0.043). Several metabolite hub features in the acylcarnitine module were significantly associated with depressive symptomatology, after correction for multiple comparisons. CONCLUSIONS: In this untargeted plasma metabolomics study among mainland Puerto Rican older adults, acylcarnitines, as a metabolite module were inversely associated with depressive symptomatology.
Assuntos
Carnitina , Depressão , Metabolômica , Humanos , Carnitina/análogos & derivados , Carnitina/sangue , Carnitina/metabolismo , Feminino , Masculino , Depressão/sangue , Depressão/metabolismo , Metabolômica/métodos , Pessoa de Meia-Idade , Idoso , Porto Rico , Estudos de Coortes , Hispânico ou Latino , Boston/epidemiologiaRESUMO
Bisphenol A (BPA) may adversely affect human health by inducing oxidative stress and irreversible damage to cells. Bioactive compounds found in some functional foods, individually or in combination, can attenuate the negative effects of BPA exposure; an example is the multi-supplement containing guarana (Gua), selenium (Se), and L-carnitine (LC) -GSC- which has already demonstrated antioxidant, genoprotective, and immunomodulatory activities. This study aimed to determine the effect of GSC and its constituents on oxidative and genotoxic alterations triggered by BPA exposure in the retinal epithelial cell line. The cells exposed to BPA (0.001, 0.01, 0.1, 1, 3, and 10 µM) to determine the lowest concentration required to induce cyto-genotoxicity. ARPE-19 cells were then concomitantly exposed to the selected BPA concentration, GSC, and its components (Gua, 1.07 mg/mL; Se, 0.178 µg/mL; and LC, 1.43 mg/mL). Flow cytometry, biochemical assays, qRT-PCR, genotoxicity, apoptosis, and cellular proliferation. Based on our results, 10 µM of BPA could induce cyto-genotoxic and oxidative alterations. BPA did not alter the Bcl-2/BAX expression ratio but induced Casp3 and Casp8 overexpression, suggesting that apoptosis was induced mainly via the extrinsic pathway. GSC partially reversed the alterations triggered by BPA in ARPE-19 cells. However, Se had unexpected negative effects on ARPE-19 cells. The multi-supplement GSC may attenuate changes in oxidative and genotoxic markers related to exposure of ARPE-19 cells to BPA. our results revealed that the antioxidant, anti-apoptotic, and genoprotective properties of GSC were not universally shared by its individual, once Se did not exhibit any positive impact.
Assuntos
Apoptose , Compostos Benzidrílicos , Carnitina , Estresse Oxidativo , Fenóis , Epitélio Pigmentado da Retina , Selênio , Fenóis/toxicidade , Compostos Benzidrílicos/toxicidade , Humanos , Selênio/farmacologia , Carnitina/farmacologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular , Paullinia/química , Dano ao DNA/efeitos dos fármacos , Antioxidantes/farmacologia , Células Epiteliais/efeitos dos fármacos , Citometria de Fluxo , Suplementos NutricionaisRESUMO
SUMMARY: Cadmium (Cd) is a toxic element that accumulates in kidney and liver. L-carnitine(LC) is a natural compound that has been shown to exhibit antioxidant activity. Aim of this study was to investigate the effect of L-carnitine against cadmium-induced changes in liver and kidney tissues in prepubertal female rats. In this study 21-day-old female Wistar Albino rats were used. Control, cadmium (2 mg/kg cadmium intraperitoneally), L-carnitine (300 mg/kg orally) and cadmium+L-carnitine groups were formed. Liver and kidney tissue sections were stained with Hematoxylin-Eosin and Masson Trichrome. Histological scoring was performed in liver and kidney. In the liver tissue given Cd, bile duct proliferation, inflammation cells and connective tissue in the portal area were decreased in treatment group. In kidneys, cadmium group treated with L-carnitine, it was observed that the capillary congestion in the kidneys decreased, but tubular dilatation continued in some places. In fibrosis scoring of the liver groups,statistically significant decrease was observed in the Cd+LC group compared to group of cadmium. In the histological scoring results of the kidney groups, statistically significant decrease in congestion and tubular epithelial degeneration was observed in the group treated with L-carnitine compared to group with cadmium. In conclusion medium-dose cadmium has toxic effects in liver and kidney of prepubertal female rats in subacute period,these effects are alleviated with L-carnitine.
El cadmio (Cd) es un elemento tóxico que se acumula en los riñones y el hígado. La L-carnitina (LC) es un compuesto natural que ha demostrado tener actividad antioxidante. El objetivo de este estudio fue investigar el efecto de la L-carnitina contra los cambios inducidos por el cadmio en los tejidos del hígado y el riñón en ratas hembra prepúberes. En este estudio se utilizaron ratas Wistar Albinas hembra de 21 días de edad. Se formaron grupos control, cadmio (2 mg/kg de cadmio por vía intraperitoneal), L- carnitina (300 mg/kg por vía oral) y cadmio + L-carnitina. Se tiñeron secciones de tejido de hígado y riñón con Hematoxilina-Eosina y tricrómico de Masson. La puntuación histológica se realizó en hígado y riñón. En el tejido hepático que recibió Cd, la proliferación de los conductos biliares, las células inflamatorias y el tejido conectivo en el área portal disminuyeron en el grupo con tratamiento. En los riñones, en el grupo de cadmio tratado con L- carnitina, se observó que la congestión capilar disminuyó, pero la dilatación tubular continuó en algunos sitios. En la puntuación de fibrosis de los grupos de hígado, se observó una disminución estadísticamente significativa en el grupo de Cd+LC en comparación con el grupo de cadmio. Los resultados de puntuación histológica de los grupos de riñón, arrojó una disminución estadísticamente significativa en la congestión y el epitelio tubular Se observó degeneración en el grupo tratado con L-carnitina en comparación con el grupo con cadmio. En conclusión, las dosis medias de cadmio tienen efectos tóxicos en el hígado y los riñones de ratas hembras prepúberes en el período subagudo; estos efectos se alivian con L-carnitina.
Assuntos
Animais , Feminino , Ratos , Cádmio/toxicidade , Carnitina/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Ratos WistarRESUMO
(1) Aims: Gut microbiota metabolites may play integral roles in human metabolism and disease progression. However, evidence for associations between metabolites and cardiometabolic risk factors is sparse, especially in high-risk Hispanic populations. We aimed to evaluate the cross-sectional and longitudinal relationships between gut microbiota related metabolites and measures of glycemia, dyslipidemia, adiposity, and incident type 2 diabetes in two Hispanic observational cohorts. (2) Methods: We included data from 670 participants of the Boston Puerto Rican Health Study (BPRHS) and 999 participants of the San Juan Overweight Adult Longitudinal Study (SOALS). Questionnaires and clinical examinations were conducted over 3 years of follow-up for SOALS and 6 years of follow-up for BPRHS. Plasma metabolites, including L-carnitine, betaine, choline, and trimethylamine N-oxide (TMAO), were measured at baseline in both studies. We used multivariable linear models to evaluate the associations between metabolites and cardiometabolic risk factors and multivariable logistic and Poisson regressions to assess associations with prevalent and incident type 2 diabetes, adjusted for potential confounding factors. Cohort-specific analyses were combined using a fixed-effects meta-analysis. (3) Results: Higher plasma betaine was prospectively associated with lower fasting glucose [-0.97 mg/dL (95% CI: -1.59, -0.34), p = 0.002], lower HbA1c [-0.02% (95% CI: -0.04, -0.01), p = 0.01], lower HOMA-IR [-0.14 (95% CI: -0.23, -0.05), p = 0.003], and lower fasting insulin [-0.27 mcU/mL (95% CI: -0.51, -0.03), p = 0.02]. Betaine was also associated with a 22% lower incidence of type 2 diabetes (IRR: 0.78, 95% CI: 0.65, 0.95). L-carnitine was associated with lower fasting glucose [-0.68 mg/dL (95% CI: -1.29, -0.07), p = 0.03] and lower HbA1c at follow-up [-0.03% (95% CI: -0.05, -0.01), p < 0.001], while TMAO was associated with higher fasting glucose [0.83 mg/dL (95% CI: 0.22, 1.44), p = 0.01] and higher triglycerides [3.52 mg/dL (95% CI: 1.83, 5.20), p < 0.0001]. Neither choline nor TMAO were associated with incident type 2 diabetes. (4) Conclusions: Higher plasma betaine showed consistent associations with a lower risk of glycemia, insulinemia, and type 2 diabetes. However, TMAO, a metabolite of betaine, was associated with higher glucose and lipid concentrations. These observations demonstrate the importance of gut microbiota metabolites for human cardiometabolic health.
Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Hispânico ou Latino , Metilaminas , Adulto , Humanos , Betaína , Carnitina , Colina , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etnologia , Glucose , Hemoglobinas Glicadas , Hispânico ou Latino/etnologia , Hispânico ou Latino/estatística & dados numéricos , Estudos Longitudinais , Porto Rico/epidemiologia , Porto Rico/etnologia , Boston/epidemiologiaRESUMO
Background: L-2-hydroxyglutaric aciduria (L2HGA) is a rare inherited autosomal recessive neurometabolic disorder caused by pathogenic variants in the L2HGDH gene which encodes mitochondrial 2-hydroxyglutarate dehydrogenase. Here, we report a case of L2HGA in a Mexican-Mayan patient with a homozygous mutation at L2HGDH gene and clinical response to vitamin supplements and levocarnitine. Case report: A 17-year-old, right-handed female patient with long-term history of seizures, developmental delay and ataxia was referred to a movement disorders specialist for the evaluation of tremor. Her brain MRI showed typical findings of L2HGA. The diagnosis was corroborated with elevated levels of 2-hydroxyglutaric acid in urine and genetic test which revealed a homozygous genetic known variant c.569C>T in exon 5 of L2HGDH gene. She was treated with levocarnitine and vitamin supplements, showing improvement in tremor and gait. Discussion: To our knowledge this is the first report of a Mexican patient with L2HGA. This case adds information about a rare condition in a different ethnic group and supports the findings of other authors which encountered symptomatic improvement with the use of flavin adenine dinucleotide (and its precursor riboflavin), and levocarnitine. Highlights: We report the first case of Mexican-Mayan patient with L2HGA showing a missense homozygous mutation in L2HGDH gene, and improvement of symptoms with vitamin supplements and levocarnitine.
Assuntos
Encefalopatias Metabólicas Congênitas , Carnitina , Tremor , Humanos , Feminino , Adolescente , Mutação/genética , Vitaminas , Oxirredutases do Álcool/genéticaRESUMO
l-carnitine (LC) transports fatty acids to the mitochondria for energy production, reducing lipid availability for peroxidation through ß-oxidation. This research examines the effect of LC supplementation to two skimmed milk-based extenders on the cryosurvival of chilled (5°C) and frozen-thawed Peruvian Paso horse spermatozoa .An initial experiment determined the optimal LC concentration (0, 1, 5, 10, 25, and 50 mM) when added to INRA-96® and UHT (skimmed milk + 6% egg yolk) extenders, using nine ejaculates from three stallions chilled for up to 96 h. Subsequently, the effect of 25 mM LC supplementation (the optimal concentration) on chilling (INRA-96) and freezing (INRA-Freeze®) extenders was evaluated using eight pooled samples from sixteen ejaculates (2 ejaculates/pool) from four stallions. Results indicated that all LC concentrations produced significantly higher values (P<0.05) for kinematic variables (total [TM] and progressive motilities, curvilinear [VCL] and straight-line [VSL] velocity, and beat-cross frequency [BCF]), and the integrity of plasma/acrosome membranes (IPIA) compared to non-supplemented chilled sperm samples for up to 96 h with both extenders. Moreover, the use of 25 mM LC was more efficient (P<0.05) in preserving the post-chilled values of velocity, BCF, and IPIA for the long term than lower LC concentrations (1-10 mM). Post-thaw values of total motility, the amplitude of lateral head displacement (ALH), and IPIA were significantly improved (P<0.05) when INRA-Freeze extender was supplemented with 25 mM LC. In conclusion, supplementation of l-carnitine to skimmed milk-based extenders enhanced kinematic variables and protected the membrane integrity in chilled and frozen-thawed Peruvian Paso horse spermatozoa.
Assuntos
Carnitina , Membrana Celular , Criopreservação , Crioprotetores , Preservação do Sêmen , Motilidade dos Espermatozoides , Espermatozoides , Animais , Masculino , Cavalos , Preservação do Sêmen/métodos , Preservação do Sêmen/veterinária , Criopreservação/métodos , Criopreservação/veterinária , Espermatozoides/efeitos dos fármacos , Carnitina/farmacologia , Crioprotetores/farmacologia , Motilidade dos Espermatozoides/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Congelamento , Fenômenos Biomecânicos/efeitos dos fármacosRESUMO
ABSTRACT: Recent large-scale multiomics studies suggest that genetic factors influence the chemical individuality of donated blood. To examine this concept, we performed metabolomics analyses of 643 blood units from volunteers who donated units of packed red blood cells (RBCs) on 2 separate occasions. These analyses identified carnitine metabolism as the most reproducible pathway across multiple donations from the same donor. We also measured l-carnitine and acyl-carnitines in 13 091 packed RBC units from donors in the Recipient Epidemiology and Donor Evaluation study. Genome-wide association studies against 879 000 polymorphisms identified critical genetic factors contributing to interdonor heterogeneity in end-of-storage carnitine levels, including common nonsynonymous polymorphisms in genes encoding carnitine transporters (SLC22A16, SLC22A5, and SLC16A9); carnitine synthesis (FLVCR1 and MTDH) and metabolism (CPT1A, CPT2, CRAT, and ACSS2), and carnitine-dependent repair of lipids oxidized by ALOX5. Significant associations between genetic polymorphisms on SLC22 transporters and carnitine pools in stored RBCs were validated in 525 Diversity Outbred mice. Donors carrying 2 alleles of the rs12210538 SLC22A16 single-nucleotide polymorphism exhibited the lowest l-carnitine levels, significant elevations of in vitro hemolysis, and the highest degree of vesiculation, accompanied by increases in lipid peroxidation markers. Separation of RBCs by age, via in vivo biotinylation in mice, and Percoll density gradients of human RBCs, showed age-dependent depletions of l-carnitine and acyl-carnitine pools, accompanied by progressive failure of the reacylation process after chemically induced membrane lipid damage. Supplementation of stored murine RBCs with l-carnitine boosted posttransfusion recovery, suggesting this could represent a viable strategy to improve RBC storage quality.
Assuntos
Carnitina , Eritrócitos , Hemólise , Carnitina/metabolismo , Humanos , Animais , Camundongos , Eritrócitos/metabolismo , Polimorfismo de Nucleotídeo Único , Envelhecimento Eritrocítico , Estudo de Associação Genômica Ampla , Masculino , Feminino , Membro 5 da Família 22 de Carreadores de Soluto/genética , Membro 5 da Família 22 de Carreadores de Soluto/metabolismo , Preservação de Sangue/métodosRESUMO
This study aims to apply machine learning models to identify new biomarkers associated with the early diagnosis and prognosis of SARS-CoV-2 infection.Plasma and serum samples from COVID-19 patients (mild, moderate, and severe), patients with other pneumonia (but with negative COVID-19 RT-PCR), and healthy volunteers (control) from hospitals in four different countries (China, Spain, France, and Italy) were analyzed by GC-MS, LC-MS, and NMR. Machine learning models (PCA and PLS-DA) were developed to predict the diagnosis and prognosis of COVID-19 and identify biomarkers associated with these outcomes.A total of 1410 patient samples were analyzed. The PLS-DA model presented a diagnostic and prognostic accuracy of around 95% of all analyzed data. A total of 23 biomarkers (e.g., spermidine, taurine, L-aspartic, L-glutamic, L-phenylalanine and xanthine, ornithine, and ribothimidine) have been identified as being associated with the diagnosis and prognosis of COVID-19. Additionally, we also identified for the first time five new biomarkers (N-Acetyl-4-O-acetylneuraminic acid, N-Acetyl-L-Alanine, N-Acetyltriptophan, palmitoylcarnitine, and glycerol 1-myristate) that are also associated with the severity and diagnosis of COVID-19. These five new biomarkers were elevated in severe COVID-19 patients compared to patients with mild disease or healthy volunteers.The PLS-DA model was able to predict the diagnosis and prognosis of COVID-19 around 95%. Additionally, our investigation pinpointed five novel potential biomarkers linked to the diagnosis and prognosis of COVID-19: N-Acetyl-4-O-acetylneuraminic acid, N-Acetyl-L-Alanine, N-Acetyltriptophan, palmitoylcarnitine, and glycerol 1-myristate. These biomarkers exhibited heightened levels in severe COVID-19 patients compared to those with mild COVID-19 or healthy volunteers.
Assuntos
Biomarcadores , COVID-19 , Humanos , COVID-19/sangue , COVID-19/diagnóstico , Biomarcadores/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Itália , Aprendizado de Máquina , Carnitina/sangue , Carnitina/análogos & derivados , França/epidemiologia , SARS-CoV-2 , Adulto , China , Prognóstico , Espanha , MultiômicaRESUMO
Obesity causes inflammation in the adipose tissue and can affect the central nervous system, leading to oxidative stress and mitochondrial dysfunction. Therefore, it becomes necessary to seek new therapeutic alternatives. Gold nanoparticles (GNPs) could take carnitine to the adipose tissue, thus increasing fatty acid oxidation, reducing inflammation, and, consequently, restoring brain homeostasis. The objective of this study was to investigate the effects of GNPs associated with carnitine on the neurochemical parameters of obesity-induced mice. Eighty male Swiss mice that received a normal lipid diet (control group) or a high-fat diet (obese group) for 10 weeks were used. At the end of the sixth week, the groups were divided for daily treatment with saline, GNPs (70 µg/kg), carnitine (500 mg/kg), or GNPs associated with carnitine, respectively. Body weight was monitored weekly. At the end of the tenth week, the animals were euthanized and the mesenteric fat removed and weighed; the brain structures were separated for biochemical analysis. It was found that obesity caused oxidative damage and mitochondrial dysfunction in brain structures. Treatment with GNPs isolated reduced oxidative stress in the hippocampus. Carnitine isolated decreased the accumulation of mesenteric fat and oxidative stress in the hippocampus. The combination of treatments reduced the accumulation of mesenteric fat and mitochondrial dysfunction in the striatum. Therefore, these treatments in isolation, become a promising option for the treatment of obesity.