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V. Lopes de Andrade
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal

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Journal article
Published: 23 August 2021 in Toxicology and Applied Pharmacology
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Metals and metalloids including lead (Pb), arsenic (As) and manganese (Mn) can occur as mixtures in occupational contexts, such as mines. These chemicals are all known to be neurotoxic and provoke changes in heme metabolism also known to induce neurotoxicity. The objective of this work was to propose a multi-biomarker (BM) methodology to screen subjects exposed to the mixture of Pb, As and Mn and assess the severity of their exposure/effects, in an individual basis. The urinary levels of the metals, dela-aminolevulinic acid (ALA) and porphyrins were determined in Portuguese miners and in a control group. The combination of Pb and As urinary levels had the highest capability to identify subjects occupationally exposed to this mixture in mines, as evaluated through Receiver Operating Characteristic (ROC) (A = 98.2%; p < 0.05), allowing that 94.2% of 86 studied subjects were properly identified and the generation of an equation indicating the odd of a subject be considered as exposed to the metal mixture. The combination of urinary ALA and porphyrins revealed to be best one to be applied in the assessment of subjects with high, intermediate, and low magnitudes of exposure/effects, with 95.7% of 46 miners classified correctly according to their severity sub-group and allowing to generate equations, which can be applied in new subjects. The proposed methodology showed a satisfactory performance, evaluating in an integrated manner the magnitude of exposure/effects of the exposed workers, may contributing to improve the control of their health.

ACS Style

V. Lopes de Andrade; D. Serrazina; M.L. Mateus; C. Batoréu; M. Ascnher; A.P. Marreilha dos Santos. Multibiomarker approach to assess the magnitude of occupational exposure and effects induced by a mixture of metals. Toxicology and Applied Pharmacology 2021, 115684 .

AMA Style

V. Lopes de Andrade, D. Serrazina, M.L. Mateus, C. Batoréu, M. Ascnher, A.P. Marreilha dos Santos. Multibiomarker approach to assess the magnitude of occupational exposure and effects induced by a mixture of metals. Toxicology and Applied Pharmacology. 2021; ():115684.

Chicago/Turabian Style

V. Lopes de Andrade; D. Serrazina; M.L. Mateus; C. Batoréu; M. Ascnher; A.P. Marreilha dos Santos. 2021. "Multibiomarker approach to assess the magnitude of occupational exposure and effects induced by a mixture of metals." Toxicology and Applied Pharmacology , no. : 115684.

Journal article
Published: 23 April 2021 in Nutrients
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The Mediterranean diet (MD) has been sponsored worldwide as a healthy and sustainable diet. Our aim was to update and compare MD adherence and food choices across several Southern European countries: Spain (SP), Portugal (PT), Italy (IT), Greece (GR), and Cyprus (CY) (MED, Mediterranean), and Bulgaria (BG) and the Republic of North Macedonia (NMK) (non-MED, non-Mediterranean). Participants (N = 3145, ≥18 y) completed a survey (MeDiWeB) with sociodemographic, anthropometric, and food questions (14-item Mediterranean Diet Adherence Screener, 14-MEDAS). The MED and non-MED populations showed moderate (7.08 ± 1.96) and weak (5.58 ± 1.82) MD adherence, respectively, with significant yet small differences across countries (SP > PT > GR > IT > CY > BG > NMK, p-value < 0.001). The MED participants scored higher than the non-MED ones for most of the Mediterranean-typical foods, with the greatest differences found for olive oil (OO) and white meat preference. In most countries, ≥70% of the participants reported quantities of red meat, butter, sweet drinks, and desserts below the recommended cutoff points, whereas <50% achieved the targets for plant-based foods, OO, fish, and wine. Being a woman and increasing age were associated with superior adherence (p-value < 0.001), but differences were rather small. Our results suggest that the campaigns carried out to support and reinforce the MD and to promote plant-based foods have limited success across Southern Europe, and that more hard-hitting strategies are needed.

ACS Style

Stefano Quarta; Marika Massaro; Mihail Chervenkov; Teodora Ivanova; Dessislava Dimitrova; Rui Jorge; Vanda Andrade; Elena Philippou; Constantinos Zisimou; Viktorija Maksimova; Katarina Smilkov; Darinka Ackova; Lence Miloseva; Tatjana Ruskovska; Georgia Deligiannidou; Christos Kontogiorgis; Julio Sánchez-Meca; Paula Pinto; María-Teresa García-Conesa. Persistent Moderate-to-Weak Mediterranean Diet Adherence and Low Scoring for Plant-Based Foods across Several Southern European Countries: Are We Overlooking the Mediterranean Diet Recommendations? Nutrients 2021, 13, 1432 .

AMA Style

Stefano Quarta, Marika Massaro, Mihail Chervenkov, Teodora Ivanova, Dessislava Dimitrova, Rui Jorge, Vanda Andrade, Elena Philippou, Constantinos Zisimou, Viktorija Maksimova, Katarina Smilkov, Darinka Ackova, Lence Miloseva, Tatjana Ruskovska, Georgia Deligiannidou, Christos Kontogiorgis, Julio Sánchez-Meca, Paula Pinto, María-Teresa García-Conesa. Persistent Moderate-to-Weak Mediterranean Diet Adherence and Low Scoring for Plant-Based Foods across Several Southern European Countries: Are We Overlooking the Mediterranean Diet Recommendations? Nutrients. 2021; 13 (5):1432.

Chicago/Turabian Style

Stefano Quarta; Marika Massaro; Mihail Chervenkov; Teodora Ivanova; Dessislava Dimitrova; Rui Jorge; Vanda Andrade; Elena Philippou; Constantinos Zisimou; Viktorija Maksimova; Katarina Smilkov; Darinka Ackova; Lence Miloseva; Tatjana Ruskovska; Georgia Deligiannidou; Christos Kontogiorgis; Julio Sánchez-Meca; Paula Pinto; María-Teresa García-Conesa. 2021. "Persistent Moderate-to-Weak Mediterranean Diet Adherence and Low Scoring for Plant-Based Foods across Several Southern European Countries: Are We Overlooking the Mediterranean Diet Recommendations?" Nutrients 13, no. 5: 1432.

Book chapter
Published: 11 February 2021 in Advances in Neurotoxicology
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Environmental exposures and/or alterations in the homeostasis of essential transition metals (ETM), such as Fe, Cu, Zn or Mn, are known to contribute to neurodegenerative diseases (ND), such as Alzheimer's Disease (AD) and Parkinson's Disease (PD). Aberrant ETM homeostasis leads to altered distributions, as significant amounts may accumulate in specific brain areas, while causing metal deficiency in others. The disruption of processes reliant on the interplay between these ETM, may lead to loss of metal balance and the ensuing neurotoxicity via shared mechanisms, such as the induction of oxidative stress (OS). Both ETM imbalance and OS may play a role, via complex positive loop processes, in primary neuropathological signatures of AD, such as the accumulation of amyloid plaques and neurofibrillary tangles (NTF), and in PD, α-Syn aggregation and loss of dopamine(DA)rgic neurons. The association between ETM imbalance and ND is rarely approached under the view that metals such as Fe, Cu, Zn and Mn, can act as dangerous endogenous neurotoxic mixtures when their control mechanisms became disrupted. In fact, their presence as mixtures implies intricacies, which should be kept in mind when developing therapies for complex disorders of metal dyshomeostasis, which commonly occur in ND.

ACS Style

Vanda Lopes de Andrade; Ana Paula Marreilha dos Santos; Michael Aschner. Neurotoxicity of metal mixtures. Advances in Neurotoxicology 2021, 5, 329 -364.

AMA Style

Vanda Lopes de Andrade, Ana Paula Marreilha dos Santos, Michael Aschner. Neurotoxicity of metal mixtures. Advances in Neurotoxicology. 2021; 5 ():329-364.

Chicago/Turabian Style

Vanda Lopes de Andrade; Ana Paula Marreilha dos Santos; Michael Aschner. 2021. "Neurotoxicity of metal mixtures." Advances in Neurotoxicology 5, no. : 329-364.

Journal article
Published: 16 December 2020 in Nutrients
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The Mediterranean diet (MD) and other lifestyle characteristics have been associated with well-being, a broad multiparameter concept that includes individual’s subjective assessment of their own well-being (SWB). Some studies have suggested that diet influences SWB, thus, this work aimed to add novel information on the association of MD and SWB in a sample of Portuguese adults. Data on sociodemographic, economic, lifestyle, diet, and SWB were collected through a self-filled online questionnaire. MD adherence was assessed by the Mediterranean Diet Adherence Screener (MEDAS) score ]. Results showed a moderate adherence to the MD in 490 Portuguese adults (mean MEDAS of 7.4 ± 2.1). A higher MD adherence was found to be significantly positively associated with women, employed individuals, a higher number of meals per day, and those with frequent contact with nature (p-value < 0.0025, using Bonferroni adjustment). As a novelty, this study divided the participants into low SWB, medium SWB, and medium to high SWB profiles (3.9 ± 1.0; 6.2 ± 1.0; 8.2 ± 1.3, respectively; p-value < 0.05), which reported significantly increasing MEDAS scores (6.5 ± 2.1; 7.3 ± 2.1; 7.8 ± 1.9; respectively, p-value < 0.05).

ACS Style

Vanda Andrade; Rui Jorge; María-Teresa García-Conesa; Elena Philippou; Marika Massaro; Mihail Chervenkov; Teodora Ivanova; Viktorija Maksimova; Katarina Smilkov; Darinka Gjorgieva Ackova; Lence Miloseva; Tatjana Ruskovska; Georgia Eirini Deligiannidou; Christos A. Kontogiorgis; Paula Pinto. Mediterranean Diet Adherence and Subjective Well-Being in a Sample of Portuguese Adults. Nutrients 2020, 12, 3837 .

AMA Style

Vanda Andrade, Rui Jorge, María-Teresa García-Conesa, Elena Philippou, Marika Massaro, Mihail Chervenkov, Teodora Ivanova, Viktorija Maksimova, Katarina Smilkov, Darinka Gjorgieva Ackova, Lence Miloseva, Tatjana Ruskovska, Georgia Eirini Deligiannidou, Christos A. Kontogiorgis, Paula Pinto. Mediterranean Diet Adherence and Subjective Well-Being in a Sample of Portuguese Adults. Nutrients. 2020; 12 (12):3837.

Chicago/Turabian Style

Vanda Andrade; Rui Jorge; María-Teresa García-Conesa; Elena Philippou; Marika Massaro; Mihail Chervenkov; Teodora Ivanova; Viktorija Maksimova; Katarina Smilkov; Darinka Gjorgieva Ackova; Lence Miloseva; Tatjana Ruskovska; Georgia Eirini Deligiannidou; Christos A. Kontogiorgis; Paula Pinto. 2020. "Mediterranean Diet Adherence and Subjective Well-Being in a Sample of Portuguese Adults." Nutrients 12, no. 12: 3837.

Journal article
Published: 27 September 2020 in Nutrients
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This study provides comprehensive validation of the 14-item Mediterranean Diet Adherence Screener (14-MEDAS) in an adult population from Greece (GR), Portugal (PT), Italy (IT), Spain (SP), Cyprus (CY), Republic of North Macedonia (NMK), and Bulgaria (BG). A moderate association between the 14-MEDAS and the reference food diary was estimated for the entire population (Pearson r = 0.573, p-value < 0.001; Intraclass Correlation Coefficient (ICC) = 0.692, p-value < 0.001) with the strongest correlation found in GR, followed by PT, IT, SP, and CY. These results were supported by kappa statistics in GR, PT, IT, and SP with ≥50% of food items exhibiting a fair or better agreement. Bland–Altman analyses showed an overestimation of the 14-MEDAS score in the whole population (0.79 ± 1.81, 95%Confidence Interval (CI) 0.61, 0.96), but this value was variable across countries, with GR, NMK, and BG exhibiting the lowest bias. Taking all analyses together, the validation achieved slightly better results in the Mediterranean countries but a definitive validation ranking order was not evident. Considering growing evidence of the shift from Mediterranean Diet (MD) adherence and of the importance of culture in making food choices it is crucial that we further improve validation protocols with specific applications to compare MD adherence across countries.

ACS Style

María-Teresa García-Conesa; Elena Philippou; Christos Pafilas; Marika Massaro; Stefano Quarta; Vanda Andrade; Rui Jorge; Mihail Chervenkov; Teodora Ivanova; Dessislava Dimitrova; Viktorija Maksimova; Katarina Smilkov; Darinka Gjorgieva Ackova; Lence Miloseva; Tatjana Ruskovska; Georgia Eirini Deligiannidou; Christos A. Kontogiorgis; Paula Pinto. Exploring the Validity of the 14-Item Mediterranean Diet Adherence Screener (MEDAS): A Cross-National Study in Seven European Countries around the Mediterranean Region. Nutrients 2020, 12, 2960 .

AMA Style

María-Teresa García-Conesa, Elena Philippou, Christos Pafilas, Marika Massaro, Stefano Quarta, Vanda Andrade, Rui Jorge, Mihail Chervenkov, Teodora Ivanova, Dessislava Dimitrova, Viktorija Maksimova, Katarina Smilkov, Darinka Gjorgieva Ackova, Lence Miloseva, Tatjana Ruskovska, Georgia Eirini Deligiannidou, Christos A. Kontogiorgis, Paula Pinto. Exploring the Validity of the 14-Item Mediterranean Diet Adherence Screener (MEDAS): A Cross-National Study in Seven European Countries around the Mediterranean Region. Nutrients. 2020; 12 (10):2960.

Chicago/Turabian Style

María-Teresa García-Conesa; Elena Philippou; Christos Pafilas; Marika Massaro; Stefano Quarta; Vanda Andrade; Rui Jorge; Mihail Chervenkov; Teodora Ivanova; Dessislava Dimitrova; Viktorija Maksimova; Katarina Smilkov; Darinka Gjorgieva Ackova; Lence Miloseva; Tatjana Ruskovska; Georgia Eirini Deligiannidou; Christos A. Kontogiorgis; Paula Pinto. 2020. "Exploring the Validity of the 14-Item Mediterranean Diet Adherence Screener (MEDAS): A Cross-National Study in Seven European Countries around the Mediterranean Region." Nutrients 12, no. 10: 2960.

Journal article
Published: 11 January 2020 in Toxicology Letters
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Exposure to high levels of persistent pollutants, such as metal mixtures, is commonly encountered by the general population especially in industrialized countries. The aim of this work was to evaluate how metal pollution in contaminated areas is reflected in terms of biomarkers (BMs) of exposure and effect in human sub-populations living in distinct non-occupational environmental contexts. Thus, four Portuguese sub-populations living in different areas of Portugal were studied: i- the exposure of each member of these sub-populations to lead (Pb), manganese (Mn) and arsenic (As) was evaluated by determining metal levels in urine; ii- biochemical changes were assessed, establishing the levels of urinary metabolites of heme biosynthesis; iii- the ability of combinations of these BMs to predict the context of exposure of each subject was tested, as to develop a tool to identify adverse health effects in these environmentally exposed populations. Concerning the combinations of BMs, heme precursors in urine (delta-aminolevulinic acid and porphyrins), were predictive of contexts of environmental exposures, with 94.2% of the studied subjects correctly identified as to their sub-population origin. The use of non-specific BMs may affirm the exposure to Pb, Mn and As, also reflecting health effects induced by a chemical environmental mixture. Our studies affirm the difficulty in establishing a metal reference population.

ACS Style

Vanda Lopes de Andrade; Madalena Cota; Daniela Serrazina; Maria Luisa Mateus; Michael Aschner; Ana Paula Marreilha dos Santos. Metal environmental contamination within different human exposure context- specific and non-specific biomarkers. Toxicology Letters 2020, 324, 46 -53.

AMA Style

Vanda Lopes de Andrade, Madalena Cota, Daniela Serrazina, Maria Luisa Mateus, Michael Aschner, Ana Paula Marreilha dos Santos. Metal environmental contamination within different human exposure context- specific and non-specific biomarkers. Toxicology Letters. 2020; 324 ():46-53.

Chicago/Turabian Style

Vanda Lopes de Andrade; Madalena Cota; Daniela Serrazina; Maria Luisa Mateus; Michael Aschner; Ana Paula Marreilha dos Santos. 2020. "Metal environmental contamination within different human exposure context- specific and non-specific biomarkers." Toxicology Letters 324, no. : 46-53.

Journal article
Published: 19 September 2018 in Journal of Toxicology and Environmental Health, Part A
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Lead (Pb), manganese (Mn) and arsenic (As) are among the major toxicants in mining environments. Miners are commonly and repeatedly exposed to this toxic mixture. Some adverse effects may appear at concentrations below environmental quality guidelines for individual mixture components. Further, Pb, Mn, and As induce common adverse outcomes, such as interferences in the cholinergic system and heme synthesis. It is thus vital to monitor miners through biomarkers (BM), such that subclinical effects may be identified at an early stage. The main objectives of this study were to evaluate the exposure of a mining population to these three metals and determine alterations in cholinergic and heme synthesis parameters. Blood and urine samples of workers (n = 60) were obtained from a Portuguese mining industry and compared with a control population (n = 80). The levels of the metals were determined in biological samples, as well as urinary heme precursor levels, delta aminolevulinic acid (ALA) and porphyrins, and blood acetylcholinesterase (AChE) activity. The miners exhibited significantly higher values of Pb and As in blood and urine compared to control. In the case of Mn near or slightly higher than limit values were found. Our data show that heme precursors may be used simultaneously with metal levels as BMs for multiple metal exposures on an individual basis, resulting in 94.3% and 95.7% accuracy, respectively, in blood and urine, for subjects correctly identified with respect to occupation. This study also revealed that biological monitoring of this working population regarding metal body burden and heme precursor accumulation is advisable.

ACS Style

Daniela C Serrazina; Vanda Lopes de Andrade; Madalena Cota; Maria Luísa Mateus; Michael Aschner; Ana Paula Marreilha Dos Santos. Biomarkers of exposure and effect in a working population exposed to lead, manganese and arsenic. Journal of Toxicology and Environmental Health, Part A 2018, 81, 983 -997.

AMA Style

Daniela C Serrazina, Vanda Lopes de Andrade, Madalena Cota, Maria Luísa Mateus, Michael Aschner, Ana Paula Marreilha Dos Santos. Biomarkers of exposure and effect in a working population exposed to lead, manganese and arsenic. Journal of Toxicology and Environmental Health, Part A. 2018; 81 (19):983-997.

Chicago/Turabian Style

Daniela C Serrazina; Vanda Lopes de Andrade; Madalena Cota; Maria Luísa Mateus; Michael Aschner; Ana Paula Marreilha Dos Santos. 2018. "Biomarkers of exposure and effect in a working population exposed to lead, manganese and arsenic." Journal of Toxicology and Environmental Health, Part A 81, no. 19: 983-997.

Journal article
Published: 23 January 2017
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Pb, As and Mn are neurotoxic metals, present as mixtures at various settings. All metals are known to interfere with cholinergic/dopaminergic neurotransmission and motor function. The main objective of this work was to assess metal mixture effects of lead (Pb), arsenic (As) and manganese (Mn) on motor activity, and to evaluate the role of each mixture component as well as their additive/synergic interactions on dopaminergic and cholinergic neurotransmission. Wistar rats were treated with 8 doses of each single metal, Pb, As and Mn, or a triple metal mixture. Motor activity was evaluated along with cholinergic/dopaminergic neurotransmission, using brain acetylcholinesterase (AChE-Br) activity and serum prolactin (PRL-S) levels, respectively. Brain concentrations of Pb, As, Mn were also quantified. The metal mixture induced decreased motor activity relative to all other groups with factor analysis revealing close proximity between AChE-Br and motor activity. Pb brain levels increased significantly as compared to all the other groups, while β coefficients of multiple regression showed that this metal was the most effective in changing AChE-Br. Significant effects of interactions among the three metals on the activity of this enzyme were also noted for the metal mixture. In conclusion, co-exposure to Pb, As and Mn mixture alters the cholinergic system and motor activity to a greater extent than the dopaminergic system. Additive/synergic interactions between Pb, As and Mn may have a relevant role in mediating these events.

ACS Style

Vanda Lopes de Andrade; Maria Luísa Mateus; M Camila Batoréu; Michael Aschner; Ap Marreilha Dos Santos. Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese. 2017, 3, 31 -42.

AMA Style

Vanda Lopes de Andrade, Maria Luísa Mateus, M Camila Batoréu, Michael Aschner, Ap Marreilha Dos Santos. Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese. . 2017; 3 (2):31-42.

Chicago/Turabian Style

Vanda Lopes de Andrade; Maria Luísa Mateus; M Camila Batoréu; Michael Aschner; Ap Marreilha Dos Santos. 2017. "Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese." 3, no. 2: 31-42.

Journal article
Published: 01 October 2015 in Toxicology Letters
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ACS Style

V.M. Andrade; M.L. Mateus; M.C. Batoréu; M. Aschner; A.P. Marreilha Dos Santos. Multi-biomarker approach to identify multiple chemical exposure. Toxicology Letters 2015, 238, S149 .

AMA Style

V.M. Andrade, M.L. Mateus, M.C. Batoréu, M. Aschner, A.P. Marreilha Dos Santos. Multi-biomarker approach to identify multiple chemical exposure. Toxicology Letters. 2015; 238 (2):S149.

Chicago/Turabian Style

V.M. Andrade; M.L. Mateus; M.C. Batoréu; M. Aschner; A.P. Marreilha Dos Santos. 2015. "Multi-biomarker approach to identify multiple chemical exposure." Toxicology Letters 238, no. 2: S149.

Review
Published: 20 February 2015 in Biological Trace Element Research
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The increasing exposure of human populations to excessive levels of metals continues to represent a matter of public health concern. Several biomarkers have been studied and proposed for the detection of adverse health effects induced by lead (Pb), arsenic (As), and manganese (Mn); however, these studies have relied on exposures to each single metal, which fails to replicate real-life exposure scenarios. These three metals are commonly detected in different environmental, occupational, and food contexts and they share common neurotoxic effects, which are progressive and once clinically apparent may be irreversible. Thus, chronic exposure to low levels of a mixture of these metals may represent an additive risk of toxicity. Building upon their shared mechanisms of toxicity, such as oxidative stress, interference with neurotransmitters, and effects on the hematopoietic system, we address putative biomarkers, which may assist in assessing the onset of neurological diseases associated with exposure to this metal mixture.

ACS Style

V. M. Andrade; Maria Luísa Mateus; M. C. Batoreu; M. Aschner; A. P. Marreilha Dos Santos. Lead, Arsenic, and Manganese Metal Mixture Exposures: Focus on Biomarkers of Effect. Biological Trace Element Research 2015, 166, 13 -23.

AMA Style

V. M. Andrade, Maria Luísa Mateus, M. C. Batoreu, M. Aschner, A. P. Marreilha Dos Santos. Lead, Arsenic, and Manganese Metal Mixture Exposures: Focus on Biomarkers of Effect. Biological Trace Element Research. 2015; 166 (1):13-23.

Chicago/Turabian Style

V. M. Andrade; Maria Luísa Mateus; M. C. Batoreu; M. Aschner; A. P. Marreilha Dos Santos. 2015. "Lead, Arsenic, and Manganese Metal Mixture Exposures: Focus on Biomarkers of Effect." Biological Trace Element Research 166, no. 1: 13-23.

Journal article
Published: 01 December 2014 in NeuroToxicology
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The neurotoxic metals lead (Pb), arsenic (As) and manganese (Mn) are ubiquitous contaminants occurring as mixtures in environmental settings. The three metals may interfere with enzymes of the heme bioshyntetic pathway, leading to excessive porphyrin accumulation, which per se may trigger neurotoxicity. Given the multi-mechanisms associated with metal toxicity, we posited that a single biomarker is unlikely to predict neurotoxicity that is induced by a mixture of metals. Our objective was to evaluate the ability of a combination of urinary porphyrins to predict the magnitude of motor activity impairment induced by a mixture of Pb/As/Mn. Five groups of Wistar rats were treated for 8 days with Pb (5mg/kg), As (60 mg/L) or Mn (10mg/kg), and the 3-metal mixture (same doses as the single metals) along with a control group. Motor activity was evaluated after the administration of the last dose and 24-hour (h) urine was also collected after the treatments. Porphyrin profiles were determined both in the urine and brain. Rats treated with the metal-mixture showed a significant decrease in motor parameters compared with controls and the single metal-treated groups. Both brain and urinary porphyrin levels, when combined and analyzed by multiple linear regressions, were predictable of motor activity (p<0.05). The magnitude of change in urinary porphyrin profiles was consistent with the greatest impairments in motor activity as determined by receiver operating characteristic (ROC) curves, with a sensitivity of 88% and a specificity of 96%. Our work strongly suggests that the use of a linear combination of urinary prophyrin levels accurately predicts the magnitude of motor impairments in rats that is induced by a mixture of Pb, As and Mn.

ACS Style

Vanda Andrade; Maria Luísa Mateus; M. Camila Batoreu; Michael Aschner; A.P. Marreilha Dos Santos. Changes in rat urinary porphyrin profiles predict the magnitude of the neurotoxic effects induced by a mixture of lead, arsenic and manganese. NeuroToxicology 2014, 45, 168 -177.

AMA Style

Vanda Andrade, Maria Luísa Mateus, M. Camila Batoreu, Michael Aschner, A.P. Marreilha Dos Santos. Changes in rat urinary porphyrin profiles predict the magnitude of the neurotoxic effects induced by a mixture of lead, arsenic and manganese. NeuroToxicology. 2014; 45 ():168-177.

Chicago/Turabian Style

Vanda Andrade; Maria Luísa Mateus; M. Camila Batoreu; Michael Aschner; A.P. Marreilha Dos Santos. 2014. "Changes in rat urinary porphyrin profiles predict the magnitude of the neurotoxic effects induced by a mixture of lead, arsenic and manganese." NeuroToxicology 45, no. : 168-177.

Journal article
Published: 28 September 2014 in Environmental Toxicology and Pharmacology
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The interference of N-acetylcysteine (NAC) on 2,5-hexanedione (2,5-HD) neurotoxicity was evaluated through behavioral assays and the analysis of urinary 2,5-HD, dimethylpyrrole norleucine (DMPN), and cysteine-pyrrole conjugate (DMPN NAC), by ESI-LC–MS/MS, in rats exposed to 2,5-HD and co-exposed to 2,5-HD and NAC. Wistar rats were treated with 4 doses of: 400 mg 2,5-HD/kg bw (group I), 400 mg 2,5-HD/kg bw + 200 mg NAC/kg bw (group II), 200 mg NAC/kg bw (group III) and with saline (group IV). The results show a significant decrease (p < 0.01) in urinary DMPN and free 2,5-HD, a significant increase (p < 0.01) in DMPN NAC excretion, and a significant recovery (p < 0.01) on motor activity in rats co-exposed to 2,5-HD + NAC, as compared with rats exposed to 2,5-HD alone. Taken together, our findings suggest that at the studied conditions NAC protects against 2,5-HD neurotoxicity and DMPN may be proposed as a new sensitive and specific biomarker of 2,5-HD neurotoxicity in animals treated with a toxic amount of 2,5-hexanedione.

ACS Style

Edite Torres; A.P. Marreilha Dos Santos; Luisa Gonçalves; Vanda Andrade; M. Camila Batoreu; Maria Luísa Mateus. Role of N-acetylcysteine in protecting against 2,5-hexanedione neurotoxicity in a rat model: Changes in urinary pyrroles levels and motor activity performance. Environmental Toxicology and Pharmacology 2014, 38, 807 -813.

AMA Style

Edite Torres, A.P. Marreilha Dos Santos, Luisa Gonçalves, Vanda Andrade, M. Camila Batoreu, Maria Luísa Mateus. Role of N-acetylcysteine in protecting against 2,5-hexanedione neurotoxicity in a rat model: Changes in urinary pyrroles levels and motor activity performance. Environmental Toxicology and Pharmacology. 2014; 38 (3):807-813.

Chicago/Turabian Style

Edite Torres; A.P. Marreilha Dos Santos; Luisa Gonçalves; Vanda Andrade; M. Camila Batoreu; Maria Luísa Mateus. 2014. "Role of N-acetylcysteine in protecting against 2,5-hexanedione neurotoxicity in a rat model: Changes in urinary pyrroles levels and motor activity performance." Environmental Toxicology and Pharmacology 38, no. 3: 807-813.

Article
Published: 09 April 2014 in Biological Trace Element Research
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Lead (Pb) continues to be a major toxic metal in the environment. Pb exposure frequently occurs in the presence of other metals, such as arsenic (As) and manganese (Mn). Continued exposure to low levels of these metals may lead to long-term toxic effects due to their accumulation in several organs. Despite the recognition that metals in a mixture may alter each other's toxicity by affecting deposition, there is dearth of information on their interactions in vivo. In this work, we investigated the effect of As and Mn on Pb tissue deposition, focusing on the kidney, brain, and liver. Wistar rats were treated with eight doses of each single metal, Pb (5 mg/Kg bw), As (60 mg/L), and Mn 10 mg/Kg bw), or the same doses in a triple metal mixture. The kidney, brain, liver, blood, and urine Pb, As, and Mn concentrations were determined by graphite furnace atomic absorption spectrophotometry. The Pb kidney, brain, and liver concentrations in the metal-mixture-treated group were significantly increased compared to the Pb-alone-treated group, being more pronounced in the kidney (5.4-fold), brain (2.5-fold), and liver (1.6-fold). Urinary excretion of Pb in the metal-mixture-treated rats significantly increased compared with the Pb-treated group, although blood Pb concentrations were analogous to the Pb-treated group. Co-treatment with As, Mn, and Pb alters Pb deposition compared to Pb alone treatment, increasing Pb accumulation predominantly in the kidney and brain. Blood Pb levels, unlike urine, do not reflect the increased Pb deposition in the kidney and brain. Taken together, the results suggest that the nephro- and neurotoxicity of "real-life" Pb exposure scenarios should be considered within the context of metal mixture exposures.

ACS Style

V. Andrade; Maria Luísa Mateus; D. Santos; M. Aschner; M. Camila Batoreu; A. P. Marreilha Dos Santos. Arsenic and manganese alter lead deposition in the rat. Biological Trace Element Research 2014, 158, 384 -91.

AMA Style

V. Andrade, Maria Luísa Mateus, D. Santos, M. Aschner, M. Camila Batoreu, A. P. Marreilha Dos Santos. Arsenic and manganese alter lead deposition in the rat. Biological Trace Element Research. 2014; 158 (3):384-91.

Chicago/Turabian Style

V. Andrade; Maria Luísa Mateus; D. Santos; M. Aschner; M. Camila Batoreu; A. P. Marreilha Dos Santos. 2014. "Arsenic and manganese alter lead deposition in the rat." Biological Trace Element Research 158, no. 3: 384-91.

Journal article
Published: 30 September 2013 in NeuroToxicology
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Lead (Pb), arsenic (As) and manganese (Mn) are neurotoxic elements that often occur in mixtures for which practically no information is available on biomarkers (BMs) for the evaluation of exposure/effects. Exposures to these metals may increase delta-aminolevulinic acid (delta-ALA), which in itself may potentiate neurotoxicity. The objective of this study was to investigate the utility of urinary delta-ALA (delta-ALA-U) levels as BM of exposure and/or neurotoxic effects induced by this mixture. Five groups of Wistar rats were treated for 8 days with Pb (5 mg/kg), As (60 mg/L), Mn (10 mg/kg), the 3-metal mixture (same doses of the single metals), and control group. Motor activity was evaluated and 24-h urine collected before and after the treatment. 24-hours (h) after the last dose, the rats were sacrificed and the brains removed for analyses. Delta-ALA and metal levels were determined in brain and urine. Co-treated rats showed a significant (p < 0.05) correlation between increased Pb, As, Mn and delta-ALA levels in the brain and decreased motor activity. Delta-ALA-U concentrations were higher in the mixture-treated group than the sum of the delta-ALA-U levels in each single-treated groups and discriminated (p < 0.05) between the mixture and untreated rats. Moreover, delta-ALA-U was correlated (p < 0.05) with brain delta-ALA levels. These results establish that treatments with this metal mixture exacerbate behavioral dysfunction, increasing most prominently brain Pb levels. This study is the first to establish that delta-ALA-U levels represent a sensitive BM of exposure/neurotoxic effect to this metal mixture.

ACS Style

Vanda Andrade; Maria Luísa Mateus; M. Camila Batoreu; Michael Aschner; A.P. Marreilha Dos Santos. Urinary delta-ALA: A potential biomarker of exposure and neurotoxic effect in rats co-treated with a mixture of lead, arsenic and manganese. NeuroToxicology 2013, 38, 33 -41.

AMA Style

Vanda Andrade, Maria Luísa Mateus, M. Camila Batoreu, Michael Aschner, A.P. Marreilha Dos Santos. Urinary delta-ALA: A potential biomarker of exposure and neurotoxic effect in rats co-treated with a mixture of lead, arsenic and manganese. NeuroToxicology. 2013; 38 ():33-41.

Chicago/Turabian Style

Vanda Andrade; Maria Luísa Mateus; M. Camila Batoreu; Michael Aschner; A.P. Marreilha Dos Santos. 2013. "Urinary delta-ALA: A potential biomarker of exposure and neurotoxic effect in rats co-treated with a mixture of lead, arsenic and manganese." NeuroToxicology 38, no. : 33-41.

Journal article
Published: 26 February 2012 in Toxicology
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Manganese (Mn) is a naturally occurring element and an essential nutrient for humans and animals. However, exposure to high levels of Mn may cause neurotoxic effects. The pathological mechanisms associated with Mn neurotoxicity are poorly understood, but several reports have established it is mediated, at least in part, by oxidative stress. The present study was undertaken to test the hypothesis that a decrease in acetylcholinesterase (AChE) activity mediates Mn-induced neurotoxicity. Groups of 6 rats received 4 or 8 intraperitoneal (i.p.) injections of 25 mg MnCl2/kg/day, every 48 h. Twenty-four hours after the last injection, brain AChE activity and the levels of F2-isoprostanes (F2-IsoPs) and F4-neuroprostanes (F4-NPs) (biomarkers of oxidative stress), as well as prostaglandin E2 (PGE2) (biomarker of neuroinflammation) were analyzed. The results showed that after either 4 or 8 Mn doses, brain AChE activity was significantly decreased (p < 0.05), to 60 ± 16% and 55 ± 13% of control levels, respectively. Both treated groups exhibited clear signs of neurobehavioral toxicity, characterized by a significant (p < 0.001) decrease in ambulation and rearings in open-field. Furthermore, Mn treatment caused a significant increase (p < 0.05) in brain F2-IsoPs and PGE2 levels, but only after 8 doses. In rats treated with 4 Mn doses, a significant increase (p < 0.05) in brain F4-NPs levels was found. To evaluate cellular responses to oxidative stress, we assessed brain nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) and Mn-superoxide dismutase (Mn-SOD, SOD2) protein expression levels. A significant increase in Mn-SOD protein expression (p < 0.05) and a trend towards increased Nrf2 protein expression was noted in rat brains after 4 Mn doses vs. the control group, but the expression of these proteins was decreased after 8 Mn doses. Taken together, these results suggest that the inhibitory effect of Mn on AChE activity promotes increased levels of neuronal oxidative stress and neuroinflammatory biomarkers.

ACS Style

Dinamene Santos; Dejan Milatovic; Vanda Lopes de Andrade; M. Camila Batoreu; Michael Aschner; Ana Paula Marreilha dos Santos. The inhibitory effect of manganese on acetylcholinesterase activity enhances oxidative stress and neuroinflammation in the rat brain. Toxicology 2012, 292, 90 -98.

AMA Style

Dinamene Santos, Dejan Milatovic, Vanda Lopes de Andrade, M. Camila Batoreu, Michael Aschner, Ana Paula Marreilha dos Santos. The inhibitory effect of manganese on acetylcholinesterase activity enhances oxidative stress and neuroinflammation in the rat brain. Toxicology. 2012; 292 (2-3):90-98.

Chicago/Turabian Style

Dinamene Santos; Dejan Milatovic; Vanda Lopes de Andrade; M. Camila Batoreu; Michael Aschner; Ana Paula Marreilha dos Santos. 2012. "The inhibitory effect of manganese on acetylcholinesterase activity enhances oxidative stress and neuroinflammation in the rat brain." Toxicology 292, no. 2-3: 90-98.

Journal article
Published: 01 February 2012 in Toxicology and Applied Pharmacology
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Chronic, excessive exposure to manganese (Mn) may induce neurotoxicity and cause an irreversible brain disease, referred to as manganism. Efficacious therapies for the treatment of Mn are lacking, mandating the development of new interventions. The purpose of the present study was to investigate the efficacy of ebselen (Ebs) and para-aminosalicylic acid (PAS) in attenuating the neurotoxic effects of Mn in an in vivo rat model. Exposure biomarkers, inflammatory and oxidative stress biomarkers, as well as behavioral parameters were evaluated. Co-treatment with Mn plus Ebs or Mn plus PAS caused a significant decrease in blood and brain Mn concentrations (compared to rats treated with Mn alone), concomitant with reduced brain E₂ prostaglandin (PGE₂) and enhanced brain glutathione (GSH) levels, decreased serum prolactin (PRL) levels, and increased ambulation and rearing activities. Taken together, these results establish that both PAS and Ebs are efficacious in reducing Mn body burden, neuroinflammation, oxidative stress and locomotor activity impairments in a rat model of Mn-induced toxicity.

ACS Style

A.P. Marreilha Dos Santos; Rui L. Lucas; Vanda Andrade; Maria Luísa Mateus; Dejan Milatovic; Michael Aschner; M. Camila Batoreu; Ana Paula Marreilha Dos Santos. Protective effects of ebselen (Ebs) and para-aminosalicylic acid (PAS) against manganese (Mn)-induced neurotoxicity. Toxicology and Applied Pharmacology 2012, 258, 394 -402.

AMA Style

A.P. Marreilha Dos Santos, Rui L. Lucas, Vanda Andrade, Maria Luísa Mateus, Dejan Milatovic, Michael Aschner, M. Camila Batoreu, Ana Paula Marreilha Dos Santos. Protective effects of ebselen (Ebs) and para-aminosalicylic acid (PAS) against manganese (Mn)-induced neurotoxicity. Toxicology and Applied Pharmacology. 2012; 258 (3):394-402.

Chicago/Turabian Style

A.P. Marreilha Dos Santos; Rui L. Lucas; Vanda Andrade; Maria Luísa Mateus; Dejan Milatovic; Michael Aschner; M. Camila Batoreu; Ana Paula Marreilha Dos Santos. 2012. "Protective effects of ebselen (Ebs) and para-aminosalicylic acid (PAS) against manganese (Mn)-induced neurotoxicity." Toxicology and Applied Pharmacology 258, no. 3: 394-402.

Journal article
Published: 01 January 1995 in Biological Trace Element Research
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Two age groups, 3 and 15 mo, were used to investigate whether age-associated changes in some parameters related to lipid peroxidation occur in the liver of male Wistar rats and to observe possible effects of dietary selenium supplementation (0.25 and 0.50 ppm) for 12 mo on the same parameters. At these experimental conditions, the most important observation was that peroxidation did not change by aging, at least until 15 mo of age. In addition, the activity of Sedependent glutathione peroxidase (GSH-Px, EC 1.11.1.9) was higher in the liver of the older animals. It is suggested that the enzyme could have a role in the unchanged hepatic peroxidation observed in aged male rats. On the other hand, an effect of dietary selenium supplementation on those parameters was not observed, probably because the selenium levels were still at an adequate plateau.

ACS Style

M. C. Santos; H. Rodrigues; Silvania Vasconcelos; V. Andrade; M. J. Lança; Ana Maria Viegas-Crespo. The effect of age and selenium on some biochemical parameters in rat liver. Biological Trace Element Research 1995, 47, 257 -261.

AMA Style

M. C. Santos, H. Rodrigues, Silvania Vasconcelos, V. Andrade, M. J. Lança, Ana Maria Viegas-Crespo. The effect of age and selenium on some biochemical parameters in rat liver. Biological Trace Element Research. 1995; 47 (1):257-261.

Chicago/Turabian Style

M. C. Santos; H. Rodrigues; Silvania Vasconcelos; V. Andrade; M. J. Lança; Ana Maria Viegas-Crespo. 1995. "The effect of age and selenium on some biochemical parameters in rat liver." Biological Trace Element Research 47, no. 1: 257-261.