RESUMEN
The Mundaú lagoon in Maceió (Alagoas, Brazil) is a crucial resource for the local population, particularly fishing communities. Recent studies have revealed potential toxic metal contamination in the lagoon, particularly with mercury (Hg) levels exceeding the maximum regulated values. This inorganic contaminant may be impacting the health of fishermen and the local population. In this context, metabolomics, a study of small-molecule metabolites, can offer insights into the physiological impact of environmental contamination on humans. Thus, volunteers from the control and exposed groups were selected, considering the main exposure criteria primarily defined by their proximity and interaction with the lagoon. Blood and urine samples were collected from the volunteers and subjected to analysis using NMR spectroscopy. The data underwent Principal Component Analysis (PCA) and Orthogonal Partial Least-Squares Discriminant Analysis (OPLS-DA) based on metabolic patterns to establish group discrimination or identification. Metabolic pathways were assessed through enrichment analysis. The study revealed several metabolic disturbances in the exposed group's urine and plasma samples compared to control group. Noteworthy findings included arginine and proline metabolism disruptions, indicative of ammonia recycling and urea cycle impairment. These changes suggest compromised ammonia detoxification in the exposed group. Disturbances in the tricarboxylic acid (TCA) cycle and the transfer of acetyl groups into mitochondria suggested systemic metabolic stress in energy metabolism. Furthermore, elevated carnitine and ketone levels may indicate compensatory responses to low TCA cycle activity. Alterations in glutamate and glutathione metabolism and imbalances in glutathione levels indicate oxidative stress and impaired detoxification. This study highlights significant metabolic changes in fishermen exposed to contaminated environments, which can affect various metabolic pathways, including energy metabolism and antioxidant processes, potentially making individuals more vulnerable to the adverse effects of environmental contaminants. Finally, this work highlights insights into the relationship between environmental contamination and metabolic pathways, particularly in regions with limited studies.
Asunto(s)
Metabolómica , Contaminantes Químicos del Agua , Brasil , Humanos , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Masculino , Monitoreo del Ambiente , Espectroscopía de Resonancia Magnética , Exposición a Riesgos Ambientales/estadística & datos numéricos , Adulto , Análisis de Componente Principal , Mercurio/sangre , Mercurio/orina , Persona de Mediana Edad , Explotaciones PesquerasRESUMEN
Thimerosal, a preservative commonly used in the pharmaceutical and cosmetic industry, has raised concerns regarding its potentially toxic effects as an organic mercury compound. Within this context, using an NMR-based metabolomics profile and chemometric analysis, zebrafish embryos were used as an in vivo model to study the effects of thimerosal in metabolic profiles after exposure to sublethal concentrations of the mercury compound. The thimerosal concentrations of 40 and 80 nM were employed, corresponding to 40% and 80% of the LC50, respectively, for zebrafish embryos. The most significant alterations in the metabolic profile included changes in carbohydrates, amino acids, nucleotides, trimethylamine-N-oxide, ethanolamine, betaine, and ethanol. Furthermore, thimerosal exposure affects various metabolic pathways, impairing the nervous system, disrupting protein metabolism, and potentially causing oxidative damage. Therefore, adopting a metabolomics approach in this investigation provided insights into the potentially implicated metabolic pathways contributing to the deleterious effects of thimerosal in biological systems.
Asunto(s)
Mercurio , Pez Cebra , Animales , Timerosal/toxicidad , Metabolómica , AminoácidosRESUMEN
Hypertensive disorders of pregnancy are closely associated with prematurity, stillbirth, and maternal morbidity and mortality. The onset of hypertensive disorders of pregnancy (HDP) is generally noticed after the 20th week of gestation, limiting earlier intervention. The placenta is directly responsible for modulating local and systemic physiology by communicating using mechanisms such as the release of extracellular vesicles, especially exosomes. In this study, we postulated that an analysis of exosome-enriched maternal plasma could provide a more focused and applicable approach for diagnosing HDP earlier in pregnancy. Therefore, the peripheral blood plasma of 24 pregnant women (11 controls, 13 HDP) was collected between 20th and 24th gestational weeks and centrifuged for exosome enrichment. Exosome-enriched plasma samples were analyzed by Raman spectroscopy and by proton nuclear magnetic resonance metabolomics (1H NMR). Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to analyze the Raman data, from the spectral region of 600-1,800 cm-1, to determine its potential to discriminate between groups. Using principal component analysis, we were able to differentiate the two groups, with 89% of all variances found in the first three principal components. In patients with HDP, most significant differences in Raman bands intensity were found for sphingomyelin, acetyl CoA, methionine, DNA, RNA, phenylalanine, tryptophan, carotenoids, tyrosine, arginine, leucine, amide I and III, and phospholipids. The 1H NMR analysis showed reduced levels of D-glucose, L-proline, L-tyrosine, glycine, and anserine in HDP, while levels of 2-hydroxyvalerate, polyunsaturated fatty acids, and very-low-density lipoprotein (VLDL) were increased. 1H NMR results were able to assign an unknown sample to either the control or HDP groups at a precision of 88.3% using orthogonal partial least squares discriminant analysis and 87% using logistic regression analysis. Our results suggested that an analysis of exosome-enriched plasma could provide an initial assessment of placental function at the maternal-fetal interface and aid HDP diagnosis, prognosis, and treatment, as well as to detect novel, early biomarkers for HDP.
RESUMEN
BACKGROUND: Crohn's disease and ulcerative colitis are the primary inflammatory bowel diseases (IBD), and its pathogenesis is related to genetic and environmental factors. Currently, the diagnosis of IBD results in a multidisciplinary approach with significant disadvantages, such as its invasive nature, time spent, and the fact that 10% of patients remain without diagnostic classification. However, new methodologies of analysis have emerged that allowed the expansion of knowledge about IBD, as the metabolomics, the study of metabolites. The presence and prevalence of such metabolites may prove to be useful as biomarkers in the diagnosis of IBD. OBJECTIVE: Analyze fecal samples for metabolic analysis in the diagnosis of inflammatory bowel diseases (IBD), providing differentiation between Crohn's disease and ulcerative colitis. METHODS: This is an observational study with 21 patients diagnosed with IBD (ulcerative colitis 11 and Crohn's disease 10) and 15 healthy controls, all with the consent and clarification. The fecal extracts of all patients are submitted to a high-resolution Nuclear Magnetic Resonance Hydrogen (1H-NMR) spectroscopy combined with multivariate and univariate pattern recognition techniques. Through the metabolomics of fecal extracts, gives us a characterization of employing a noninvasive approach. RESULTS: We identify some metabolites, such as lactate, succinate, alanine, and tyrosine, in the Crohn's disease fecal samples, and leucine, alanine, and tyrosine in the ulcerative colitis fecal samples. All the amino acids presented positive covariance for disease correlation. CONCLUSION: The results showed different metabolic profiles between IBD patients and healthy volunteers based on 1H-NMR analysis of fecal extracts. Moreover, the approach discriminated patients with Crohn's disease and ulcerative colitis. The metabolomics analysis is promising as a novel diagnostic technique for further IBD recognition and surveillance. New studies are necessary to validate these findings.
Asunto(s)
Enfermedades Inflamatorias del Intestino , Heces , Humanos , MetabolómicaRESUMEN
ABSTRACT BACKGROUND: Crohn's disease and ulcerative colitis are the primary inflammatory bowel diseases (IBD), and its pathogenesis is related to genetic and environmental factors. Currently, the diagnosis of IBD results in a multidisciplinary approach with significant disadvantages, such as its invasive nature, time spent, and the fact that 10% of patients remain without diagnostic classification. However, new methodologies of analysis have emerged that allowed the expansion of knowledge about IBD, as the metabolomics, the study of metabolites. The presence and prevalence of such metabolites may prove to be useful as biomarkers in the diagnosis of IBD. OBJECTIVE: Analyze fecal samples for metabolic analysis in the diagnosis of inflammatory bowel diseases (IBD), providing differentiation between Crohn's disease and ulcerative colitis. METHODS: This is an observational study with 21 patients diagnosed with IBD (ulcerative colitis 11 and Crohn's disease 10) and 15 healthy controls, all with the consent and clarification. The fecal extracts of all patients are submitted to a high-resolution Nuclear Magnetic Resonance Hydrogen (1H-NMR) spectroscopy combined with multivariate and univariate pattern recognition techniques. Through the metabolomics of fecal extracts, gives us a characterization of employing a noninvasive approach. RESULTS: We identify some metabolites, such as lactate, succinate, alanine, and tyrosine, in the Crohn's disease fecal samples, and leucine, alanine, and tyrosine in the ulcerative colitis fecal samples. All the amino acids presented positive covariance for disease correlation. CONCLUSION: The results showed different metabolic profiles between IBD patients and healthy volunteers based on 1H-NMR analysis of fecal extracts. Moreover, the approach discriminated patients with Crohn's disease and ulcerative colitis. The metabolomics analysis is promising as a novel diagnostic technique for further IBD recognition and surveillance. New studies are necessary to validate these findings.
RESUMO CONTEXTO: A doença de Crohn e retocolite ulcerativa são as principais doenças inflamatórias intestinais (DII), e sua patogênese está relacionada a fatores genéticos e ambientais. Atualmente, o diagnóstico de DII resulta em uma abordagem multidisciplinar e apresenta desvantagens significativas, como sua natureza invasiva, tempo gasto e o fato de 10% dos pacientes permanecerem sem classificação diagnóstica. No entanto, surgiram novas metodologias de análise que permitiram ampliar o conhecimento sobre a DII, como a metabolômica, o estudo dos metabólitos. A presença e a prevalência desses metabólitos podem ser úteis como biomarcadores no diagnóstico da DII. OBJETIVO: Avaliar as amostras fecais por análise metabolômica no diagnóstico de DII, diferenciando os perfis metabólicos entre doença de Crohn e retocolite ulcerativa. MÉTODOS: Estudo observacional com 36 indivíduos (doença de Crohn 11, retocolite ulcerativa 10 e 15 controles saudáveis), todos com consentimento esclarecido. Os extratos fecais de todos os pacientes são submetidos a uma espectroscopia de alta resolução por ressonância magnética nuclear de hidrogênio (1H-RMN) combinada com técnicas de reconhecimento de padrões multivariados e univariados. Por meio da metabolômica utilizando extratos fecais, foi possível obter uma caracterização adequada das doenças inflamatórias intestinais através de uma abordagem não invasiva. RESULTADOS: Foi possível identificar os seguintes metabólitos nos pacientes com doença de Crohn: lactato, succinato, alanina e tirosina e, no grupo retocolite ulcerativa encontrou-se leucina, alanina e tirosina. Todos os aminoácidos apresentaram covariância positiva para a doença. CONCLUSÃO: Os resultados demonstraram diferentes perfis metabólicos entre pacientes com DII e voluntários saudáveis, com base na análise por 1H-RMN dos extratos fecais. Além disso, pacientes com doença de Crohn e retocolite ulcerativa também podem ser discriminados usando essa abordagem. A análise metabolômica é promissora como uma nova técnica não invasiva de diagnóstico para melhor reconhecimento das DII. Novos estudos são necessários para validar esses achados.