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Introduction: Metal carpentry includes a wide range of work activities such as welding and cutting metallic components, use of solvents and paints. Therefore, the employees in these types of activities are mainly exposed to welding fumes and volatile organic solvents. Here, we present an NMR-based metabolomic approach for assessing urinary profiles of workers in the same company that are exposed to two different risk factors. Methods: The study enrolled 40 male subjects exposed to welding fumes, 13 male subjects exposed to volatile organic compounds of a metal carpentry company, and 24 healthy volunteers. All samples were collected, in the middle of the working week at fast. Thirty-five urinary metabolites belonging to different chemical classes such as amino acids, organic acids and amines were identified and quantified. Results were processed by multivariate statistical analysis for identifying significant metabolites for each working group examined, compared to controls. Results: Workers exposed to welding fumes displayed urinary increase in glutamine, tyrosine, taurine, creatine, methylguanidine and pseudouridine associated to oxidative impairment, while workers exposed to volatile organic compounds showed higher urinary levels of branched chain aminoacids. Conclusion: Our work identified specific urinary profile related to each occupational exposure, even if it is below the threshold limit values.
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Contaminantes Ocupacionales del Aire , Espectroscopía de Resonancia Magnética , Metabolómica , Exposición Profesional , Compuestos Orgánicos Volátiles , Soldadura , Humanos , Masculino , Compuestos Orgánicos Volátiles/orina , Exposición Profesional/efectos adversos , Exposición Profesional/análisis , Adulto , Contaminantes Ocupacionales del Aire/orina , Contaminantes Ocupacionales del Aire/análisis , Persona de Mediana EdadRESUMEN
Due to its chemical properties, styrene is largely employed in the manufacturing of several products including rubber, polymers and resins, and it is particularly suitable for shipbuilding industry purposes. In this context, the main exposure to styrene occurs in occupational settings. Despite its widespread use, its long-term effects on human health at the occupational level are still unclear. The aim of this pilot study was to evaluate changes in styrene exposure biomarkers related to the metabolic and oxidative stress profiles in the urine of seventeen shipyard workers and seventeen non-exposed subjects. Urinary metabolites were assessed by means of NMR spectroscopy, including mandelic and phenylglyoxylic acids; four oxidative stress biomarkers, namely 8-oxo-7,8-dihydroguanine, 8-oxo-7,8-dihydroguanosine, and 8-oxo-7,8-dihydro-2'-deoxyguanosine and 3-nitrotyrosine, were evaluated via HPLC-MS/MS. The metabolic profiles of exposed workers showed both long- and short-term metabolic responses to styrene exposure compared to non-exposed subjects. From the comparison between non-exposed and before-shift workers, only 8-oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine levels were significantly different (long term exposure response). At the same time, comparing the non-exposed group with after-shift workers, we observed lower levels of pseudouridine and 1-methylnicotinamide and higher glutamine levels in after-shift workers. The comparison between before-shift and after-shift workers showed that 8-oxo-7,8-dihydroguanine significantly increased after the shift, suggesting its involvement in the exposure to styrene (short-term exposure response). The obtained results, although preliminary, allow us to lay the basis for further human studies aimed at establishing a global understanding of styrene metabolism.
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Introduction: In the shipbuilding industry, workers are exposed to a variety of dangerous chemicals, styrene being one of them. The International Agency for Research on Cancer classified styrene as a chemical belonging to group 2A, which means it is probably carcinogenic to humans. This study aimed at evaluating the oxidative stress effects due to occupational exposure to styrene and other chemicals. Materials and methods: Styrene urinary metabolites, such as mandelic acid and phenylglyoxylic acid, and the urinary biomarkers of oxidative stress, i.e., oxidation products of DNA and RNA and of proteins, were measured in a group of 17 workers and compared to the concentrations found in a group of 17 healthy volunteers who had not been exposed to chemicals. Results and discussion: Statistically significant differences were found for 8-oxo-7,8-dihydroguanine (8-oxoGua) and 8-oxo-7,8-dihydro-2'-deoxiguanosine (8-oxodGuo) concentrations that are higher in workers than in the control group. The workers performing the tasks of painting are the most exposed to styrene and show higher concentrations of 8-oxo-7,8-dihydroguanosine (8-oxoGuo). Workers performing the tasks of wood refining and welding are less exposed to styrene but have higher concentrations of 8-oxoGua and 8-oxodGuo. Conclusion: The exposure scenario in shipbuilding is a complex one, in which different xenobiotics are simultaneously present. The oxidative stress effect biomarkers, obtained from the oxidation product of RNA and DNA, are promising, sensitive, but not specific.
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The honey bee is an important pollinator insect susceptible to environmental contaminants. We investigated the effects of a waste fire event on elemental content, oxidative stress, and metabolic response in bees fed different nutrients (probiotics, Quassia amara, and placebo). The level of the elements was also investigated in honey and beeswax. Our data show a general increase in elemental concentrations in all bee groups after the event; however, the administration of probiotics and Quassia amara help fight oxidative stress in bees. Significantly lower concentrations of Ni, S, and U for honey in the probiotic group and a general and significant decrease in elemental concentrations for beeswax in the probiotic group and Li in the Quassia amara group were observed after the fire waste event. The comparison of the metabolic profiles through pre- and post-event PCA analyses showed that bees treated with different feeds react differently to the environmental event. The greatest differences in metabolic profiles are observed between the placebo-fed bees compared to the others. This study can help to understand how some stress factors can affect the health of bees and to take measures to protect these precious insects.
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Pecan nuts (Carya illinoinensis (Wangenh.) K. Koch) contain the highest number of phytochemicals of all nuts, are a natural source of unsaturated fatty acids and other nutrients and can be considered an important addition to the Mediterranean diet al.though several studies have been carried out on pecans, employing several analytical techniques, no systematic study of the metabolic profile is available in literature. In this study, the metabolic profile of pecan nuts of three different cultivars was analysed by Nuclear Magnetic Resonance Spectroscopy. The cultivars compared were Wichita, Stuart, and Sioux, all grown in Italy in the same pedoclimatic conditions. 31 metabolites were identified and 28 were quantified and the three species were differentiated based on multivariate PCA analysis. The differences among them, and the levels of scutellarein and GABA, in particular, were attributed to the adaptation of the plants to the climate in their original areas.
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BACKGROUND: Red beetroot is known to be a health-promoting food. However, little attention is placed on intestinal bioactive compound absorption. The aim of the study was to assess the urinary red beetroot juice (RBJ) intake biomarkers and possible differences in RBJ's micronutrient absorption at rest or after physical exercise. METHODS: This is a three-armed, single-blind study, involving seven healthy volunteers which were randomly divided into three groups and alternatively assigned to three experimental sessions: RBJ intake at rest, RBJ intake with physical activity, and placebo intake with physical activity. For each session, urine samples were collected before and 120, 180, and 240 min after the intake of RBJ or placebo. The same sampling times were employed for the experimental session at rest. The RBJ metabolic composition was also characterized to identify the urinary biomarkers derived from the intake. RESULTS: 4-methylpyridine-2-carboxylic acid, dopamine-3-O-sulfate, glutamine, and 3-hydroxyisobutyrate were identified as RBJ intake biomarkers. Physical activity significantly increased only the dopamine-3-O-sulfate excretion 120 min after RBJ intake. CONCLUSIONS: Urinary dopamine-3-O-sulfate is related to RBJ dopamine content, while 4-methylpyridine-2-carboxylic acid is a betanin or betalamic acid catabolite. The different excretions of these metabolites following physical activity suggest a possible effect on the RBJ uptake depending on different transport processes through the mucosa, namely diffusion-mediated transport for dopamine and saturable transcellular transport for betalamic acid derivatives. These results open new perspectives in improving the absorption of natural bioactive molecules through physical activity.
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Dopamina , Ejercicio Físico , Humanos , Antioxidantes , Ácidos Carboxílicos , Método Simple Ciego , SulfatosRESUMEN
The most commonly used antiviral treatment against hepatitis C virus is a combination of direct-acting antivirals (DAAs) and ribavirin (RBV), which leads to a shortened duration of therapy and a sustained virologic response until 98%. Nonetheless, several dose-related side effects of RBV could limit its applications. This study aims to measure the urinary concentration of RBV and its main metabolites in order to evaluate the drug metabolism ability of HCV patients and to evaluate the adverse effects, such as anemia, with respect to RBV metabolite levels. RBV and its proactive and inactive metabolites were identified and quantified in the urine of 17 HCV males with severe liver fibrosis using proton nuclear magnetic resonance (1H-NMR) at the fourth week (TW4) and at the twelfth week of treatment (EOT). Four prodrug urinary metabolites, including RBV, were identified and three of them were quantified. At both the TW4 and EOT stages, six HCV patients were found to maintain high concentrations of RBV, while another six patients maintained a high level of RBV proactive metabolites, likely due to nucleosidase activity. Furthermore, a negative correlation between the reduction in hemoglobin (Hb) and proactive forms was observed, according to RBV-triphosphate accumulation causing the hemolysis. These findings represent a proof of concept regarding tailoring the drug dose in relation to the specific metabolic ability of the individual, as expected by the precision medicine approach.
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Hepatitis C Crónica , Hepatitis C , Antivirales/efectos adversos , Quimioterapia Combinada , Hepacivirus , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Masculino , Medicina de Precisión , Proteínas Recombinantes/farmacología , Ribavirina/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: The objective of this study is to evaluate the effects of traffic on human health comparing biomonitoring data measured during the COVID-19 lockdown, when restrictions led to a 40% reduction in airborne benzene in Rome and a 36% reduction in road traffic, to the same parameters measured in 2021. METHODS: Biomonitoring was performed on 49 volunteers, determining the urinary metabolites of the most abundant traffic pollutants, such as benzene and PAHs, and oxidative stress biomarkers by HPLC/MS-MS, 28 elements by ICP/MS and metabolic phenotypes by NMR. RESULTS: Means of s-phenylmercaputric acid (SPMA), metabolites of naphthalene and nitropyrene in 2020 are 20% lower than in 2021, while 1-OH-pyrene was 30% lower. A reduction of 40% for 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodGuo) and 60% for 8-oxo-7,8-dihydroguanine (8-oxoGua) were found in 2020 compared to 2021. The concentrations of B, Co, Cu and Sb in 2021 are significantly higher than in the 2020. NMR untargeted metabolomic analysis identified 35 urinary metabolites. Results show in 2021 a decrease in succinic acid, a product of the Krebs cycle promoting inflammation. CONCLUSIONS: Urban pollution due to traffic is partly responsible for oxidative stress of nucleic acids, but other factors also have a role, enhancing the importance of communication about a healthy lifestyle in the prevention of cancer diseases.
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In recent studies, oxidative stress after scuba diving has been explored by measuring urinary biomarkers in volunteers under controlled conditions. Dive depth and duration, water temperature, and workload are all variables that can elicit metabolic responses. A controlled diving experiment was performed in an indoor pool at 20, 30, and 40 m depths at a water temperature of 32 °C, on three different days. Samples of urine from five male scuba divers were taken before diving and at four time points after diving, and then tested for their concentration of five different oxidative stress biomarkers by means of liquid chromatography tandem mass spectrometry and by 1H nuclear magnetic resonance metabolomics analysis. The results showed no variation in the five biomarkers after diving, but a decreasing trend was observed over the three days, with no differences among the three depths. The lack of effect on oxidative stress biomarkers has been attributed to the comfortable water temperature and to the absence of exercise in the divers during the experiment. Instead, an increase in hypoxanthine excretion, which can be considered a biomarker sensitive to hyperbaric exposure, was found after diving. Finally, the results suggest a physiological mechanism of metabolic adaptation to a new condition.
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Buceo , Ácidos Nucleicos , Biomarcadores/orina , Humanos , Hipoxantina , Masculino , AguaRESUMEN
SUMMARY: Antineoplastic drugs are used to treat cancer, having their therapeutic effect by inhibiting the cell division process. Although cancer cells, due to their rapid growth, are more sensitive to the toxic effects of chemotherapeutic agents, healthy cells and tissues may also be damaged. Many studies show acute and chronic toxicity both in patients treated with chemotherapy and in exposed workers. In fact, exposure to these substances can also be linked to the formation of different types of secondary tumors. The International Agency on Research on Cancer (IARC) included some antineplastic drugs in Group 1 (carcinogenic to humans), in Group 2A (probable carcinogens for In recent years, many studies have evidenced the presence of antineoplastic drug contamination on work surfaces, materials and floors and based on these observations, international and national guidelines have been published to limit occupational exposure, with particular attention to procedures post-preparation of chemotherapy to limit as much as possible the accumulation of contaminated residues. The aim of the following study is to determine the effectiveness of the degradation of four antineoplastic drugs: 5-fluorouracil, azacitidine, cytarabine and irinotecan using a low concentration of sodium hypochlorite solution (0.115%). The analytical platform used to monitor the degradation course of the substances under examination was hydrogen nuclear magnetic spectroscopy (1H NMR). In the same experimental conditions the effectiveness of the degradation of the same antineoplastic drugs with a 99.9% ethanol solution was also evaluated. The study showed that the best degradation efficiency (> 90% ) is obtained with the hypochlorite solution after 15 minutes.
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Antineoplásicos/química , Carcinógenos/química , Espectroscopía de Resonancia Magnética/métodos , Hipoclorito de Sodio/farmacología , Antineoplásicos/efectos adversos , Antineoplásicos/clasificación , Azacitidina/química , Carcinógenos/clasificación , Citarabina/química , Descontaminación/métodos , Interacciones Farmacológicas , Etanol/farmacología , Fluorouracilo/química , Humanos , Ácido Hipocloroso/farmacología , Irinotecán/química , Exposición Profesional/efectos adversos , Exposición Profesional/prevención & control , Datos Preliminares , Cloruro de Sodio/farmacología , Factores de TiempoRESUMEN
Occupational exposure to hyperbaric atmosphere occurs in workers who carry out their activity in environments where breathing air pressure is at least 10% higher than pressure at sea level, and operations can be divided in Dry or Wet activities. The increased air pressure implies the formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), consumption of antioxidants and reduction of antioxidant enzyme activity, causing lipid peroxidation, DNA and RNA damage. The present study was aimed to establish the relation between hyperbaric exposure and metabolic changes due to ROS unbalance, by means of the determination of urinary biomarkers of oxidatively generated damage to DNA and RNA during a controlled diving session. The investigated biomarkers were 8-oxo-7,8-dihydroguanine (8-oxoGua), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo). The experimental session involved six experienced divers subjected to 3 atmospheres absolute for 30 minutes in two different experiments, in both dry and wet conditions. Urine samples were collected at t = 0 (before exposure) and 30 (end of exposure),90, 240, 480 and 720 minutes. The concentration of 8-oxoGua, 8-oxoGuo, and 8-oxodGuo was determined by isotopic dilution high performance liquid chromatography (HPLC-MS/MS). In all subjects there is an increase of the urinary excretion of 8oxo-Guo and 8oxo-dGuo, in both conditions, after 1.5 - 4 hours from the start of the experiment, and that the values tend to return to the baseline after 12 hours. Besides that, also the nucleic magnetic resonance (NMR)-based untargeted metabolomics was employed for the same objective on the same samples, confirming a different metabolic response in the subjects exposed to dry or wet conditions. In particular, the observed hypoxanthine urinary level increases during the underwater hyperbaric exposure, in agreement with the trend observed for 8-oxoGuo and 8-oxodGuo levels. Present results confirmed the relationship between exposure and oxidative stress and depicted a clear temporal trend of the investigated biomarkers. Due to the possible negative consequences of oxidative stress on workers, present research shows a new line in term of risk prevention.
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8-Hidroxi-2'-Desoxicoguanosina/orina , Presión Atmosférica , Conducción de Automóvil , Guanosina/análogos & derivados , Exposición Profesional/efectos adversos , Tiempo (Meteorología) , Adulto , Biomarcadores/orina , Femenino , Guanosina/orina , Humanos , Masculino , Persona de Mediana Edad , Exposición Profesional/análisis , Estrés OxidativoRESUMEN
Bacterial canker of Actinidia, caused by the bacterium Pseudomonas syringae pv. actinidiae (Psa), is the most serious disease of these plants worldwide. Leaves of three species of Actinidia, namely A. chinensis var. chinensis, A. chinensis var. deliciosa and A. arguta, having different degrees of tolerance to Psa, were analyzed by Nuclear Magnetic Resonance spectroscopy. Aqueous extracts of leaves were studied and several metabolites, classified as organic acids, amino acids, carbohydrates, phenols and other metabolites, were identified by 1D and 2D NMR experiments and quantified. The metabolic profiles of these species were compared through univariate statistical analysis ANOVA and multivariate PCA. Levels of metabolites with known antibacterial activity, such as caffeic and chlorogenic acids, were observed to be higher in the A. arguta samples. Moreover, these metabolites have different Pearson correlation patterns among the three Actinidia species, suggesting a difference at the phenylpropanoid biosynthetic pathway.
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Actinidia/microbiología , Hojas de la Planta/microbiología , Pseudomonas syringae/patogenicidad , Antibacterianos , Espectroscopía de Resonancia Magnética , Enfermedades de las Plantas/microbiología , Extractos Vegetales/metabolismo , Hojas de la Planta/metabolismo , Especificidad de la EspecieRESUMEN
The metabolic profiling of pistachio (Pistacia vera) aqueous extracts from two different cultivars, namely 'Bianca' and 'Gloria', was monitored over the months from May to September employing high field NMR spectroscopy. A large number of water-soluble metabolites were assigned by means of 1D and 2D NMR experiments. The change in the metabolic profiles monitored over time allowed the pistachio development to be investigated. Specific temporal trends of amino acids, sugars, organic acids and other metabolites were observed and analysed by multivariate Partial Least Squares (PLS) analysis. Statistical analysis showed that while in the period from May to September there were few differences between the two cultivars, the ripening rate was different.
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Espectroscopía de Resonancia Magnética/métodos , Metaboloma/fisiología , Pistacia/fisiología , Aminoácidos/análisis , Metabolismo de los Hidratos de Carbono , Carbohidratos/análisis , Metabolómica/métodos , Monitoreo Fisiológico/métodos , Pistacia/químicaRESUMEN
The aim of our study was to investigate whether occupational exposure to antineoplastic drugs (AND) resulted in genetic damage, possibly indicative of adverse health effects in the long term. We performed a chromosomal aberrations (CA) analysis in peripheral blood lymphocytes (PBL) of a group of 76 trained nurses occupationally exposed to AND. Furthermore, we analysed whether genetic polymorphisms in four metabolic genes of the glutathione S-transferase (GST) family involved in antineoplastic drugs detoxification (GSTM1, GSTT1, GSTP1, GSTA1) had any effect on the yield of chromosomal aberrations in nurses exposed to antineoplastic agents. The exposed group showed a very significant increase of genetic damage (p<0.0001) potentially indicative of an increased risk of cancer. Unexpectedly, besides the elevated level of chromatid-type aberrations usually related to exposure to chemical agents, we found also severe chromosome damages such as chromosome deletions and dicentric chromosomes, usually related to radiation exposure. No significant association was detected between all GSTs genotypes and chromosome damage. In conclusion, our data show how the occupational exposure to AND is associated to a potential cancer risk, suggesting that current prevention methods do not completely eliminate opportunities for exposure and supporting the need to improve the actual safety practices.
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Antineoplásicos/efectos adversos , Aberraciones Cromosómicas/inducido químicamente , Glutatión Transferasa/genética , Mutágenos/efectos adversos , Exposición Profesional/efectos adversos , Polimorfismo de Nucleótido Simple , Adulto , Deleción Cromosómica , Femenino , Predisposición Genética a la Enfermedad , Glutatión Transferasa/metabolismo , Humanos , Linfocitos/efectos de los fármacos , Linfocitos/patología , Masculino , Persona de Mediana Edad , Translocación GenéticaRESUMEN
Health-care workers handling antineoplastic agents may be exposed to extremely low doses of these drugs. Very sensitive and specific analytical methods are therefore needed for biological monitoring. The aim of this study was to develop and validate a method for trace level determination of doxorubicin, epirubicin, daunorubicin and idarubicin in human urine, using epi-daunorubicin as an internal standard. Solid-phase extraction (SPE) was used for sample preparation. Urine samples were loaded onto Bond Elut C18 cartridges. The analytes were eluted in methylene chloride/2-propanol (1:1, v/v) and then evaporated to dryness. The residue was reconstituted with the mobile phase prior to high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) analysis. Quantitation of each analyte was performed using the multiple reaction monitoring (MRM) method. The urine assay was linear over the range 0.1-2.0 microg/L, with a lower limit of quantification (LLOQ) of 0.10 microg/L for doxorubicin and epirubicin, and 0.03 microg/L for daunorubicin and idarubicin. The respective limits of detection (LODs) were 0.04 and 0.01 microg/L. The precision and accuracy of the assay were determined on three different days. The within-series precision was found to be always less than 13.9% for all the analytes. The overall precision expressed as relative standard deviation (RSD) was always less than 10.6%. The recovery of anthracyclines was assessed at two concentrations of the range tested (0.1 and 2.0 microg/L) and it ranged from 87.7% (daunorubicin) to 102.0% (doxorubicin) and from 79.1% (daunorubicin) to 90.7% (idarubicin) for the lower and the higher level, respectively, with a RSD always less than 9.1%. The uncertainty of the present assay was also evaluated and the combined uncertainty was always less than 20% over all the days of the validation study. This is the first method that makes use of LC/MS/MS for the biological monitoring of occupational exposure to anthracyclines.
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Antraciclinas/orina , Cromatografía Líquida de Alta Presión/métodos , Microquímica/métodos , Exposición Profesional/análisis , Personal de Hospital , Espectrometría de Masa por Ionización de Electrospray/métodos , Urinálisis/métodos , Antineoplásicos/orina , Humanos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
The separation of paraquat, diquat, and difenzoquat bipyridilium herbicides and ethyl viologen as internal standard is shown. The separation has been carried out using a fused silica capillary with a high-sensitivity detection cell for a capillary electrophoresis system and with a diode array detector. The experiments have been performed using phosphate buffer 50 mM at pH = 4 and pH = 7. The effect of methanol has also been studied when used as an organic modifier. Different voltages and electrokinetic conditions have been used to optimize the separation. Twenty Kv voltage and 10 Kv for 3 sec for injection have been found to be reliable conditions of separation at pH 4 without organic modifier.