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1.
Plasma Concentration of Essential and Toxic Trace Elements After Brazil Nut Intake: Results from a Randomized Controlled Trial.
Duarte, GBS, Reis, BZ, Rogero, MM, Barbosa, F, Cercato, C, Cozzolino, SMF
Biological trace element research. 2023;(3):1112-1117
Abstract
Brazil nut (BN) is a good source of essential nutrients, but little is known about the content of other components, such as toxic elements. Moreover, the high consumption of BN could probably contribute to increased levels of toxic and essential elements in the blood. Thus, this study aimed to evaluate the concentration of essential and toxic trace elements in BN and their concentration in plasma of obese women after regular intake of BN. A randomized controlled clinical trial was carried out with 55 subjects that were randomly assigned to either the Brazil nut group (BN) (n = 29) or the control group (CO) (n = 26) and followed up for 2 months. The BN group consumed one unit of Brazil nut per day, and the CO group did not receive any intervention. The concentration of essential elements (zinc, copper, manganese, and cobalt) and toxic (barium, lead, and cadmium) in BN samples and plasma of obese women (before and after the intervention) were determined by inductively coupled plasma mass spectrometry. Barium followed by copper, and manganese were the trace elements present in higher amounts in Brazil nuts. After the BN intervention period was observed an increase in plasma cadmium (p = 0.002) and a reduction of plasma manganese (p < 0.001) levels. In conclusion, our findings suggest that the regular consumption of BN from the Brazilian Amazon rainforest contributes to the intake of essential trace elements and can be considered safe regarding the content of heavy metals.
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2.
Momordica balsamina: phytochemistry and pharmacological potential of a gifted species.
Ramalhete, C, Gonçalves, BMF, Barbosa, F, Duarte, N, Ferreira, MU
Phytochemistry reviews : proceedings of the Phytochemical Society of Europe. 2022;(2):617-646
Abstract
Momordica balsamina L. (Cucurbitaceae), frequently named balsam apple, southern balsam pear or African pumpkin, is a vegetable with high nutritional value, being mostly used as food in sub-Saharan Africa. It has also been largely used in traditional medicine to treat several diseases, such as malaria fevers and diabetes. As a member of the Cucurbitaceae family, the main constituents are cucurbitane-type triterpenoids, with different oxidation patterns, named cucurbitacins. This review aims at summarizing our contribution to the phytochemical study of M. balsamina and the evaluation of the isolated cucurbitacins and derivatives as multidrug resistance reversers in cancer cells and bacteria. In this way, the selective antiproliferative activity against multidrug resistant cancer cells of cucurbitacins obtained from M. balsamina, their ability as P-glycoprotein inhibitors in cancer cells overexpressing this ABC transporter, as well as efflux pump inhibitors in resistant bacteria strains are reviewed. Moreover, the in vitro antimalarial activity of cucurbitacins and acyl derivatives against the blood and liver-stages of Plasmodium strains, and the in vivo activity of selected compounds is also reviewed. Besides our work, edible and medicinal uses, and other studies mainly reporting the biological activities of M. balsamina extracts, such as antidiabetic, antibacterial, anti-inflammatory, and antioxidant properties are also addressed.
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3.
Mercury and cancer: Where are we now after two decades of research?
Skalny, AV, Aschner, M, Sekacheva, MI, Santamaria, A, Barbosa, F, Ferrer, B, Aaseth, J, Paoliello, MMB, Rocha, JBT, Tinkov, AA
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2022;:113001
Abstract
The present study aims to review epidemiological and experimental toxicology studies published over the last two decades linking mercury (Hg) exposure and carcinogenesis, with a special emphasis on the potential underlying mechanisms. While some epidemiological studies have observed a strong association between environmental/occupational Hg exposure levels, measured in blood, toenail, and hair, and cancer risk and mortality, others failed to reveal any association. In experimental models, high-dose Hg exposure has been linked with cytotoxicity, whereas low-dose exposure was posited to induce proliferative responses in both normal and cancerous cells by interference with estrogen receptor, ERK1/2, JNK, NADPH-oxidase and, potentially, Nrf2 signaling. Combined with reduced apoptosis and pro-survival signaling upon low-dose Hg exposure, accumulation of DNA lesions in cells may predispose to an increased risk of malignant transformation. In addition, the pro-oxidant activity of Hg species may induce oxidative DNA modifications and inhibits DNA repair mechanisms. Furthermore, epigenetic effects of Hg exposure seem to contribute to the carcinogenic activity, although the particular mechanisms have yet to be characterized. Therefore, even after 20 years of research, one cannot consider Hg as a non-carcinogenic agent, whereas specific mechanisms of Hg-induced toxicity may promote carcinogenic risk.
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4.
Ferroptosis as a mechanism of non-ferrous metal toxicity.
Aschner, M, Skalny, AV, Martins, AC, Sinitskii, AI, Farina, M, Lu, R, Barbosa, F, Gluhcheva, YG, Santamaria, A, Tinkov, AA
Archives of toxicology. 2022;(9):2391-2417
Abstract
Ferroptosis is a recently discovered form of regulated cell death, implicated in multiple pathologies. Given that the toxicity elicited by some metals is linked to alterations in iron metabolism and induction of oxidative stress and lipid peroxidation, ferroptosis might be involved in such toxicity. Although direct evidence is insufficient, certain pioneering studies have demonstrated a crosstalk between metal toxicity and ferroptosis. Specifically, the mechanisms underlying metal-induced ferroptosis include induction of ferritinophagy, increased DMT-1 and TfR cellular iron uptake, mitochondrial dysfunction and mitochondrial reactive oxygen species (mitoROS) generation, inhibition of Xc-system and glutathione peroxidase 4 (GPX4) activity, altogether resulting in oxidative stress and lipid peroxidation. In addition, there is direct evidence of the role of ferroptosis in the toxicity of arsenic, cadmium, zinc, manganese, copper, and aluminum exposure. In contrast, findings on the impact of cobalt and nickel on ferroptosis are scant and nearly lacking altogether for mercury and especially lead. Other gaps in the field include limited studies on the role of metal speciation in ferroptosis and the critical cellular targets. Although further detailed studies are required, it seems reasonable to propose even at this early stage that ferroptosis may play a significant role in metal toxicity, and its modulation may be considered as a potential therapeutic tool for the amelioration of metal toxicity.
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5.
Effects of home confinement on mental health and lifestyle behaviours during the COVID-19 outbreak: insights from the ECLB-COVID19 multicentre study.
Ammar, A, Trabelsi, K, Brach, M, Chtourou, H, Boukhris, O, Masmoudi, L, Bouaziz, B, Bentlage, E, How, D, Ahmed, M, et al
Biology of sport. 2021;38(1):9-21
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Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the respiratory syndrome coronavirus 2 (SARS-CoV-2). To curb the spread of the 2020 pandemic, social distancing, self-isolation and nationwide lockdown measures were put in place. These measures along with hygiene care are recognized as the most effective ways to curb the spread of disease. However; the weakening of social contacts can result in anxiety, frustration, panic attacks, loss or sudden increase of appetite, insomnia, depression, mood swings, delusions, fear, sleep disorders, and suicidal/domestic violence. The purpose of the study is to provide scientific data to help identify risk factors for the psychosocial strain during the COVID-19 outbreak. The study is an international cross-disciplinary online survey and was circulated in April 2020. 1047 replies were analysed from this preliminary phase. The results show a significant difference in all tested parameters and therefore reveal a large burden for mental wellbeing combined with a tendency towards an unhealthy lifestyle during, compared to before, the confinement enforced by the COVID-19 pandemic. These results highlight the importance for policy makers to consider strategies to promote wellbeing during future confinements.
Abstract
Although recognised as effective measures to curb the spread of the COVID-19 outbreak, social distancing and self-isolation have been suggested to generate a burden throughout the population. To provide scientific data to help identify risk factors for the psychosocial strain during the COVID-19 outbreak, an international cross-disciplinary online survey was circulated in April 2020. This report outlines the mental, emotional and behavioural consequences of COVID-19 home confinement. The ECLB-COVID19 electronic survey was designed by a steering group of multidisciplinary scientists, following a structured review of the literature. The survey was uploaded and shared on the Google online survey platform and was promoted by thirty-five research organizations from Europe, North Africa, Western Asia and the Americas. Questions were presented in a differential format with questions related to responses "before" and "during" the confinement period. 1047 replies (54% women) from Western Asia (36%), North Africa (40%), Europe (21%) and other continents (3%) were analysed. The COVID-19 home confinement evoked a negative effect on mental wellbeing and emotional status (P < 0.001; 0.43 ≤ d ≤ 0.65) with a greater proportion of individuals experiencing psychosocial and emotional disorders (+10% to +16.5%). These psychosocial tolls were associated with unhealthy lifestyle behaviours with a greater proportion of individuals experiencing (i) physical (+15.2%) and social (+71.2%) inactivity, (ii) poor sleep quality (+12.8%), (iii) unhealthy diet behaviours (+10%), and (iv) unemployment (6%). Conversely, participants demonstrated a greater use (+15%) of technology during the confinement period. These findings elucidate the risk of psychosocial strain during the COVID-19 home confinement period and provide a clear remit for the urgent implementation of technology-based intervention to foster an Active and Healthy Confinement Lifestyle AHCL).
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Mortality in Hemodialysis Patients with COVID-19, the Effect of Paricalcitol or Calcimimetics.
Arenas Jimenez, MD, González-Parra, E, Riera, M, Rincón Bello, A, López-Herradón, A, Cao, H, Hurtado, S, Collado, S, Ribera, L, Barbosa, F, et al
Nutrients. 2021;(8)
Abstract
BACKGROUND In COVID-19 patients, low serum vitamin D (VD) levels have been associated with severe acute respiratory failure and poor prognosis. In regular hemodialysis (HD) patients, there is VD deficiency and markedly reduced calcitriol levels, which may predispose them to worse outcomes of COVID-19 infection. Some hemodialysis patients receive treatment with drugs for secondary hyperparathyroidism, which have well known pleiotropic effects beyond mineral metabolism. The aim of this study was to evaluate the impact of VD status and the administration of active vitamin D medications, used to treat secondary hyperparathyroidism, on survival in a cohort of COVID-19 positive HD patients. METHODS A cross-sectional retrospective observational study was conducted from 12 March to 21 May 2020 in 288 HD patients with positive PCR for SARS-CoV2. Patients were from 52 different centers in Spain. RESULTS The percent of HD patients with COVID-19 was 6.1% (288 out of 4743). Mortality rate was 28.4% (81/285). Three patients were lost to follow-up. Serum 25(OH)D (calcidiol) level was 17.1 [10.6-27.5] ng/mL and was not significantly associated to mortality (OR 0.99 (0.97-1.01), p = 0.4). Patients receiving active vitamin D medications (16/94 (17%) vs. 65/191(34%), p = 0.003), including calcimimetics (4/49 (8.2%) vs. 77/236 (32.6%), p = 0.001), paricalcitol or calcimimetics (19/117 (16.2%) vs. 62/168 (36.9%); p < 0.001), and also those on both paricalcitol and calcimimetics, to treat secondary hyperparathyroidism (SHPTH) (1/26 (3.8%) vs. 80/259 (30.9%), p < 0.001) showed a lower mortality rate than patients receiving no treatment with either drug. Multivariate Cox regression analysis confirmed this increased survival. CONCLUSIONS Our findings suggest that the use of paricalcitol, calcimimetics or the combination of both, seem to be associated with the improvement of survival in HD patients with COVID-19. No correlation was found between serum VD levels and prognosis or outcomes in HD patients with COVID-19. Prospective studies and clinical trials are needed to support these findings.
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Economic decision-making in the continuum between healthy aging and Alzheimer's Disease: A systematic review of 20 years of research.
Fernandes, C, Macedo, I, Barbosa, F, Marques-Teixeira, J
Neuroscience and biobehavioral reviews. 2021;:1243-1263
Abstract
The effect of pathological aging on economic decision-making is a topic of major relevance as impairments in this domain place older adults at increased risk for financial abuse. This review aims to characterize decision-making across the continuum that goes from healthy aging to Alzheimer's Dementia. We included 42 studies comparing patients with Mild Cognitive Impairment (MCI) and healthy older adults, patients with Alzheimer's Disease (AD) and healthy older adults, and patients with MCI and patients with AD. Substantial evidence emerged suggesting that both MCI as AD affect economic decision-making. However, a non-negligible number of behavioural tasks failed to find significant differences between patients and controls, and no differences were reported between patients with MCI and AD. On the contrary, measures of financial capacity reached more robust findings, showing that healthy older adults had better performance than patients, while MCI patients showed better performance than AD patients. This review presents the main conclusions that may be drawn from significant findings, as well as the hypotheses and recommendations for future research.
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Phospholipids modifications in human hepatoma cell lines (HepG2) exposed to silver and iron oxide nanoparticles.
Adeyemi, JA, Sorgi, CA, Machado, ART, Ogunjimi, AT, Gardinassi, LGA, Nardini, V, Faccioli, LH, Antunes, LMG, Barbosa, F
Archives of toxicology. 2020;(8):2625-2636
Abstract
Metallic nanoparticles such as silver (Ag NPs) and iron oxide (Fe3O4 NPs) nanoparticles are high production volume materials due to their applications in various consumer products, and in nanomedicine. However, their inherent toxicities to human cells remain a challenge. The present study was aimed at combining lipidomics data with common phenotypically-based toxicological assays to gain better understanding into cellular response to Ag NPs and Fe3O4 NPs exposure. HepG2 cells were exposed to different concentrations (3.125, 6.25, 12.5, 25, 50 and 100 µg/ml) of the nanoparticles for 24 h, after which they were assayed for toxic effects using toxicological assays like cytotoxicity, mutagenicity, apoptosis and oxidative stress. The cell membrane phospholipid profile of the cells was also performed using shotgun tandem mass spectrometry. The results showed that nanoparticles exposure resulted in concentration-dependent cytotoxicity as well as reduced cytokinesis-block proliferation index (CBPI). Also, there was an increase in the production of ROS and superoxide anions in exposed cells compared to the negative control. The lipidomics data revealed that nanoparticles exposure caused a modulation of the phospholipidome of the cells. A total of 155 lipid species were identified, out of which the fold changes of 23 were significant. The high number of differentially changed phosphatidylcholine species could be an indication that inflammation is one of the major mechanisms of toxicity of the nanoparticles to the cells.
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Cytotoxicity, mutagenicity, oxidative stress and mitochondrial impairment in human hepatoma (HepG2) cells exposed to copper oxide, copper-iron oxide and carbon nanoparticles.
Adeyemi, JA, Machado, ART, Ogunjimi, AT, Alberici, LC, Antunes, LMG, Barbosa, F
Ecotoxicology and environmental safety. 2020;:109982
Abstract
The increasing application of nanomaterials in various fields such as drug delivery, cosmetics, disease detection, cancer treatment, food preservation etc. has resulted in high levels of engineered nanoparticles in the environment, thus leading to higher possibility of direct or indirect interactions between these particles and biological systems. In this study, the toxic effects of three commercially available nanomaterials; copper oxide nanoparticles, copper-iron oxide nanopowders and carbon nanopowders were determined in the human hepatoma HepG2 cells using various toxicological assays which are indicative of cytotoxicity (MTT and neutral red assays), mutagenicity (cytokinesis-block micronucleus assay), oxidative stress (total reactive oxygen species and superoxide anion production) and mitochondrial impairment (cellular oxygen consumption). There was increased cytotoxicity, mutagenicity, and mitochondrial impairment in the cells treated with higher concentrations of the nanomaterials, especially the copper oxide nanoparticles. The fold production of reactive oxygen species was similar at the concentrations tested in this study but longer exposure duration resulted in production of more superoxide anions. The results of this study showed that copper oxide nanoparticles are highly toxic to the human HepG2 cells, thus implying that the liver is a target organ in human for copper oxide nanoparticles toxicity.
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10.
Genetic variants in selenoprotein genes modulate biomarkers of selenium status in response to Brazil nut supplementation (the SU.BRA.NUT study).
Donadio, JLS, Rogero, MM, Guerra-Shinohara, EM, Barbosa, F, Desmarchelier, C, Borel, P, Sneddon, AA, Hesketh, JE, Cozzolino, SMF
Clinical nutrition (Edinburgh, Scotland). 2019;(2):539-548
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Abstract
BACKGROUND The beneficial effects of selenium (Se) to human health are exerted by selenoproteins, which can be quantified in blood and used as biomarkers of Se status. Different responses of Se biomarkers after supplementation with selenomethionine and sodium selenite have been observed and some of them could be due to genetic polymorphisms, mainly single nucleotide polymorphisms (SNPs). Brazil nuts are known to be the richest natural source of Se. OBJECTIVE Investigate how genetic variations in selenoprotein genes modulate biomarkers of Se status in response to Brazil nut supplementation. METHODS The SU.BRA.NUT study was a four month interventional trial which involved healthy volunteers of both genders, selected in University of Sao Paulo. The supplementation was done with one Brazil nut a day for 8 weeks, followed by 8 weeks of washout. Blood samples were collected at 5 time points: baseline, 4 and 8 weeks of supplementation and 4 and 8 weeks of washout for analysis of five biomarkers of Se status - erythrocyte GPx1 (Glutathione Peroxidase 1) activity, plasma GPx3 activity, plasma Se, erythrocyte Se, and plasma selenoprotein P. The gene expression of GPX1, SELENOP, SELENOF and SELENOS was done before and after 8 weeks of supplementation. The volunteers were genotyped for SNPs in GPX1 (rs1050450, rs3811699 and rs1800699), GPX4 (rs713041), SELENOP (rs3877899 and rs7579), SELENOF (rs5845) and SELENOS (rs34713741). RESULTS A total of 130 volunteers finished the protocol. The concentrations of four biomarkers of Se status increased significantly after 4 and 8 weeks of supplementation, being modulated by gender. In addition, erythrocyte GPx1 activity was associated with rs1050450, rs713041 and rs5845. Plasma Se was associated with rs7579 and selenoprotein P with plasma Se at baseline. Nut supplementation significantly increased GPX1 mRNA expression only in subjects with CC genotype at rs1050450. SELENOP mRNA expression was significantly lower in subjects with GG genotype at rs7579 before and after supplementation. CONCLUSION Genetic variations in GPX1 and SELENOP genes are associated with different responses of molecular and biochemical biomarkers of Se status after Brazil nut supplementation in healthy Brazilians. The SU.BRA.NUT study was registred at www.clinicaltrials.gov as NCT 03111355.