Maria Fernanda Hornos Carneiro

Inorganic and Methylmercury Levels in Plasma are Differentially Associated with Age, Gender, and Oxidative Stress Markers in a Population Exposed to Mercury Through Fish Consumption

This study aimed to determine the concentrations of plasma methylmercury (Me-Hg) and inorganic mercury (I-Hg) in a population exposed to Me-Hg. In addition, associations between each form of mercury (Hg) and gender, age, plasma selenium (Se), and oxidative stress markers were also investigated. The mean plasma I-Hg level was 5.7 μg/L while the mean for plasma Me-Hg was 3.6 μg/L, representing approximately 59 and 41% of the total Hg in blood, respectively. However, several plasma samples contained higher percentages of Me-Hg. Age displayed a direct linkage with plasma I-Hg levels, whereas gender did not correlate with any of the Hg species. In addition, fish intake was only correlated with and a predictor of plasma Me-Hg, suggesting that plasma I-Hg levels originated endogenously through a demethylation reaction that needs to be verified. Further, plasma Me-Hg was markedly correlated with adverse effects to a greater extent than plasma I-Hg and may be considered a valuable, reliable internal dose biomarker for Hg in chronically Me-Hg- exposed individuals.

A systematic study of the disposition and metabolism of mercury species in mice after exposure to low levels of thimerosal (ethylmercury).

Thimerosal (TM) is an ethylmercury (etHg)-containing preservative used in some vaccines despite very limited knowledge on the kinetics and direct interaction/effects in mammals׳ tissues after exposure. Thus, this study aimed to evaluate the kinetics of Hg species in mice in a time course analysis after intramuscular injection of TM, by estimating Hg half-lives in blood and tissues. Mice were exposed to one single intramuscular dose of 20 µg of Hg as TM. Blood, brain, heart, kidney and liver were collected at 0.5 hour (h), 1 h, 8 h, 16 h, 144 h, 720 h and 1980 h after TM exposure (n=4). Hg species in animal tissues were identified and quantified by speciation analysis via liquid chromatography hyphenated with inductively coupled mass spectrometry (LC-ICP-MS). It was found that the transport of etHg from muscle to tissues and its conversion to inorganic Hg (inoHg) occur rapidly. Moreover, the conversion extent is modulated in part by the partitioning between EtHg in plasma and in whole blood, since etHg is rapidly converted in red cells but not in a plasma compartment. Furthermore, the dealkylation mechanism in red cells appears to be mediated by the Fenton reaction (hydroxyl radical formation). Interestingly, after 0.5 h of TM exposure, the highest levels of both etHg and inoHg were found in kidneys (accounting for more than 70% of the total Hg in the animal body), whereas the brain contributed least to the Hg body burden (accounts for <1.0% of total body Hg). Thirty days after TM exposure, most Hg had been excreted while the liver presented the majority of the remaining Hg. Estimated half-lives (in days) were 8.8 for blood, 10.7 for brain, 7.8 for heart, 7.7 for liver and 45.2 for kidney. Taken together, our findings demonstrated that TM (etHg) kinetics more closely approximates Hg(2+) than methylmercury (meHg) while the kidney must be considered a potential target for etHg toxicity.

Low Concentrations of Selenium and Zinc in Nails are Associated with Childhood Asthma

The purpose of this study was to investigate possible associations between Zn, Se, Cu, Mn, and Co concentrations in nails and asthma in a young population from a Southern Brazil city. Additionally, correlations between these chemical elements among asthmatic and non-asthmatic children were evaluated. Before nail collection (n = 165), children were asked to complete the International Study of Asthma and Allergies in Childhood questionnaire. The concentrations of trace elements were determined by inductively coupled plasma mass spectrometry. The chi-square test was used to evaluate the association between element concentrations in nails and the respiratory outcome. To evaluate correlations between the elements, we used the Spearman correlation test. For all tests, the significance level was set at 95% (P ≤ 0.05). Children included in the highest quartile of nail Se and Zn concentration presented a fivefold decrease in the prevalence ratio of asthma while children in the lowest Se range presented an almost 2.5-fold increase in the asthma prevalence ratio. There were weak to strong correlations between Cu vs. Zn, Cu vs. Co, Cu vs. Se, Zn vs. Se, Zn vs. Mn, and Mn vs. Co in both asthmatic and non-asthmatic children. Interestingly, non-asthmatics also presented correlations between Co vs. Se and Zn. Taken together, our results clearly demonstrated an association between concentrations of selenium and zinc and childhood asthma and the usefulness of nail as a noninvasive matrix to detect minerals imbalance in asthma patients.

Evaluation of the Concentration of Nonessential and Essential Elements in Chicken, Pork, and Beef Samples Produced in Brazil

Food safety is a global concern. Meat represents the most important protein source for humans. Thus, contamination of meat products by nonessential elements is a ready source of human exposure. In addition, knowledge of the concentration of essential elements is also relevant with respect to human nutrition. The aim of the present study was to determine the concentration of 17 elements in pork, beef, and chicken produced in Brazil. Meat samples were analyzed by inductively coupled plasma mass spectrometry. The estimated daily intake for nonessential elements including arsenic (As), cadmium (Cd), lead (Pb), mercury (Hg), and antimony (Sb) through meat consumption is below the toxicological reference values. However, high levels were detected for the nonessential element cesium (Cs), mainly in beef samples, an observation that deserves future studies to identify the source of contamination and potential adverse consequences.

Manioc Flour Consumption as a Risk Factor for Lead Poisoning in the Brazilian Amazon

Recent studies reported elevated blood lead (Pb) levels in riparian populations of the Amazon. For this reason, the aim of the present study was to assess the risk to riparians in the Brazilian Amazon to Pb exposure due to the intake of contaminated manioc flour. Lead levels were determined in whole blood (n = 74) and in manioc flour samples (n = 30) in three different communities. Mean blood Pb levels were 16.8 μg/dl, with individuals living in Açaituba presenting the highest mean blood Pb level (22.4 μg/dl), followed by Nova Canaã (17.3 μg/dl) and Santa Cruz (9.8 μg/dl). The minimum blood Pb level found was 0.83 μg/dl and the maximum was 44.3 μg/dl. The estimated daily intake (EDI) was calculated and compared to the benchmark dose lower confidence limit (BMDL) for neurotoxicity. Mean Pb in manioc flour was 0.34 μg/g while EDI was 79 μg/d, corresponding to 260% of the BMDL (varying from 168 to 308%). This finding is of great importance since this high EDI may exert adverse effects on the nervous system of this population. Manioc flour intake may thus present considerable risk of Pb exposure in this region. Risk management strategies and further studies on adverse effects in this population are needed.

Background Values for Essential and Toxic Elements in Children’s Nails and Correlation with Hair Levels

Human nails are an attractive matrix for assessing environmental exposures to toxic elements as well as the deficiency of essential elements since it is noninvasively collected and can be stored at room temperature. However, reference or baseline levels in nonexposed and healthy populations are not yet established. Then, the aims of this study were (a) to estimate background values for essential and toxic elements in nails from a healthy young population in southern Brazil and (b) to evaluate possible correlations between essential and toxic elements in nails. Furthermore, this report took part of a recent study of background values in the hair of a young population. Thus, correlations between chemical elements in nails and hair were also evaluated. Nails were collected from healthy children (n = 126), and element concentrations were determined by inductively coupled plasma mass spectrometry. This study provides new and reliable reference concentrations for toxic and essential elements in children’s nails. The results can be used as reference values for epidemiological or clinical investigations based on trace elements in nails. Additionally, we also showed weak to strong correlations between Cu, Mg, Mn, Se, and Zn levels in nails and hair.

Protective effects of niacin against methylmercury-induced genotoxicity and alterations in antioxidant status in rats

ABSTRACT This study investigates the potential beneficial effects of niacin (NA; vitamin B3) supplementation in rats chronically exposed to methylmercury (MeHg). Animals were randomly assigned to one of 4 groups (n = 6): Group I, control, received distilled water by gavage; Group II, received MeHg (100 µg/kg/d) by gavage; Group III, received NA (50 mg/kg/d) in drinking water; Group IV, received MeHg (100 µg/kg/d) by gavage + NA (50 mg/kg/d) in drinking water. Biochemical parameters levels of glucose, triglycerides, total cholesterol and fractions, and enzyme activities aspartate transaminase (AST) and alanine transaminase (ALT) were determined. Further, oxidative stress markers activity of glutathione peroxidase (GPx) and catalase (CAT) activity, as well as levels of reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide, were examined, and the comet assay was performed, using blood/plasma. Hg levels were measured in blood, brain, and kidneys of animals. Our results demonstrated that NA reduced adverse effects produced by MeHg. The mechanism underlying these effects appears to be related to the intrinsic antioxidant potential of NA. Considering the beneficial effects attributed to NA following MeHg exposure and that fish are the main source of both NA and MeHg, future studies need to evaluate the potential counteractive effect of NA against the adverse consequences of MeHg exposure in fish-eating populations.

Evaluation of distribution, redox parameters, and genotoxicity in Wistar rats co-exposed to silver and titanium dioxide nanoparticles

ABSTRACT The increasing production of silver nanoparticles (AgNPs) and titanium dioxide nanoparticles (TiO2NPs) has resulted in their elevated concentrations in the environment. This study was, therefore, aimed at determining the distribution, redox parameters, and genotoxic effects in male Wistar rats that were treated with either AgNP or TiO2NP individually, as well as under a co-exposure scenario. Animals were exposed via oral gavage to either sodium citrate buffer (vehicle), 0.5 mg/kg/day TiO2NP, 0.5 mg/kg/day AgNP or a mixture of TiO2NPs and AgNPs. Exposure lasted 45 days after which rats were sacrificed, and tissue biodistribution of Ag and Ti measured. The blood concentration of glutathione (GSH) and activities of glutathione peroxidase (GPx) and catalase (CAT) were determined while the genotoxicity was analyzed using the comet assay in peripheral blood and liver cells. The tissue concentrations of Ag followed the order; blood > liver > kidneys while for Ti the order was kidneys > liver > blood. There was no significant change in the measured redox parameters in animals that were exposed to TiO2NPs. However, there was a significant increase in GSH levels accompanied by a reduction in the GPx activity in AgNP-treated and co-exposed groups. The individual or co-exposure to TiO2NP and AgNP did not markedly induce genotoxicity in blood or liver cells. Data showed that TiO2NP did not produce significant oxidative stress or genotoxicity in rats at the dose used in this study while the same dose level of AgNPs resulted in oxidative stress, but no noticeable adverse genotoxic effects.

Thimerosal induces apoptotic and fibrotic changes to kidney epithelial cells in vitro

Thimerosal is an ethyl mercury‐containing compound used mainly in vaccines as a bactericide. Although the kidney is a key target for mercury toxicity, thimerosal nephrotoxicity has not received the same attention as other mercury species. The aim of this study was to determine the potential cytotoxic mechanisms of thimerosal on human kidney cells. Human kidney proximal tubular epithelial (HK2) cells were exposed for 24 h to thimerosal (0–2 µM), and assessed for cell viability, apoptosis, and cell proliferation; expression of proteins Bax, nuclear factor‐κB subunits, and transforming growth factor‐β1 (TGFβ1); mitochondrial health (JC‐1, MitoTracker Red CMXRos); and fibronectin levels (enzyme‐linked immunosorbent assay). Thimerosal diminished HK2 cell viability and mitosis, promoted apoptosis, impaired the mitochondrial permeability transition, enhanced Bax and TGFβ1 expression, and augmented fibronectin secretion. This is the first report about kidney cell death and pro‐fibrotic mechanisms promoted by thimerosal. Collectively, these in vitro results demonstrate that (1) thimerosal induces kidney epithelial cell apoptosis via upregulating Bax and the mitochondrial apoptotic pathway, and (2) thimerosal is a potential pro‐fibrotic agent in human kidney cells. We suggest that new evidence on toxicity as well as continuous surveillance in terms of fibrogenesis is required concerning thimerosal use.

Phytoremediation Potential of Maná-Cubiu (Solanum sessiliflorum Dunal) for the Deleterious Effects of Methylmercury on the Reproductive System of Rats

Methylmercury, organic form of mercury, can increase the number of abnormal sperm and decrease sperm concentration and testosterone levels possibly due to the damage caused by reactive species to germ and Leydig cells. Maná-cubiu (Solanum sessiliflorum Dunal) is a native fruit from Amazon rich in iron, zinc, niacin, pectin, and citric acid, used in foods, beverages, and medicinal purposes, since it has been useful for treatment of various diseases caused by oxidative stress or nutritional deficiency. Therefore, this study evaluated the phytoremediation potential of this fruit on damages caused by exposure to MeHg on sperm quantity and quality and the histological aspect of the testis and epididymis. Wistar male rats (n = 20) were randomly allocated into four groups: Control group (received distilled water), MeHg group (140 μg/Kg), Solanum group (1% of fruit Maná-cubiu on chow), and Solanum plus MeHg group (same treatment as MeHg and Solanum group). The organs were weighted, histopathology; sperm morphology and counts were obtained. The results showed reduction in body weight gain, testis weights, reduced sperm production, and increased histopathological abnormalities in the MeHg-treated group. However, treatment with Solanum plus MeHg revealed a protective effect of this fruit on damages caused by MeHg.