Dehydrodieugenol isolated from Ocotea cymbarum induces cell death in human breast cancer cell lines by dysregulation of intracellular copper concentration.

In this work, two neolignans - dehydrodieugenol (1) and dehydrodieugenol B (2) - were isolated from leaves of Ocotea cymbarum (H. B. K.) Ness. (Lauraceae). When tested against two human breast cancer cell lines (MCF7 and MDA-MB-231), compound 1 was inactive (IC50 > 500 µM) whereas compound 2 displayed IC50 values of 169 and 174 µM, respectively. To evaluate, for the first time in the literature, the synergic cytotoxic effects of compounds 1 and 2 with ion Cu2+, both cell lines were incubated with equimolar solutions of these neolignans and Cu(ClO4)2·6H2O. Obtained results revealed no differences in cytotoxicity upon the co-administration of compound 2 and Cu2+. However, the combination of compound 1 and Cu2+ increases the cytotoxicity against MCF7 and MDA-MB-231 cells, with IC50 values of 165 and 204 µM, respectively. The activity of compound 1 and Cu2+ in MCF7 spheroids regarding the causes/effects considering the tumoral microenvironment were accessed using fluorescence staining and imaging by fluorescence microscopy. This analysis enabled the observation of a higher red filter fluorescence intensity in the quiescence zone and the necrotic core, indicating a greater presence of dead cells, suggesting that the combination permeates the spheroid. Finally, using ICP-MS analysis, the intracellular copper disbalance caused by mixing compound 1 and Cu2+ was determined quantitatively. The findings showcased a 50-fold surge in the concentration of Cu2+ compared with untreated cells (p > 0.0001) - 18.7 ng of Cu2+/mg of proteins and 0.37 ng of Cu2+/mg of protein, respectively. Conversely, the concentration of Cu2+ in cells treated with compound 1 was similar to values of the negative control group (0.29 ng of Cu2+/mg of protein). This alteration allowed us to infer that compound 1 combined with Cu2+ induces cell death through copper homeostasis dysregulation.

The Impact of Hydroxytyrosol on the Metallomic-Profile in an Animal Model of Alzheimer's Disease.

It is undeniable that as people get older, they become progressively more susceptible to neurodegenerative illnesses such as Alzheimer's disease (AD). Memory loss is a prominent symptom of this condition and can be exacerbated by uneven levels of certain metals. This study used inductively coupled plasma mass spectrometry (ICP-MS) to examine the levels of metals in the blood plasma, frontal cortex, and hippocampus of Wistar rats with AD induced by streptozotocin (STZ). It also tested the effects of the antioxidant hydroxytyrosol (HT) on metal levels. The Barnes maze behavior test was used, and the STZ group showed less certainty and greater distance when exploring the Barnes maze than the control group. The results also indicated that the control group and the STZ + HT group exhibited enhanced learning curves during the Barnes maze training as compared to the STZ group. The ICP-MS analysis showed that the STZ group had lower levels of cobalt in their blood plasma than the control group, while the calcium levels in the frontal cortex of the STZ + HT group were higher than in the control group. The most important finding was that copper levels in the frontal cortex from STZ-treated animals were higher than in the control group, and that the STZ + HT group returned to equivalent levels to the control group. The antioxidant HT can restore copper levels to their basal physiological state. This finding may help explain HT's potential beneficial effect in AD-patients.

Pluronic F-127 Hydrogels Containing Copper Oxide Nanoparticles and a Nitric Oxide Donor to Treat Skin Cancer.

Melanoma is a serious and aggressive type of skin cancer with growing incidence, and it is the leading cause of death among those affected by this disease. Although surgical resection has been employed as a first-line treatment for the early stages of the tumor, noninvasive topical treatments might represent an alternative option. However, they can be irritating to the skin and result in undesirable side effects. In this context, the potential of topical polymeric hydrogels has been investigated for biomedical applications to overcome current limitations. Due to their biocompatible properties, hydrogels have been considered ideal candidates to improve local therapy and promote wound repair. Moreover, drug combinations incorporated into the polymeric-based matrix have emerged as a promising approach to improve the efficacy of cancer therapy, making them suitable vehicles for drug delivery. In this work, we demonstrate the synthesis and characterization of Pluronic F-127 hydrogels (PL) containing the nitric oxide donor S-nitrosoglutathione (GSNO) and copper oxide nanoparticles (CuO NPs) against melanoma cells. Individually applied NO donor or metallic oxide nanoparticles have been widely explored against various types of cancer with encouraging results. This is the first report to assess the potential and possible underlying mechanisms of action of PL containing both NO donor and CuO NPs toward cancer cells. We found that PL + GSNO + CuO NPs significantly reduced cell viability and greatly increased the levels of reactive oxygen species. In addition, this novel platform had a huge impact on different organelles, thus triggering cell death by inducing nuclear changes, a loss of mitochondrial membrane potential, and lipid peroxidation. Thus, GSNO and CuO NPs incorporated into PL hydrogels might find important applications in the treatment of skin cancer.

Cellular prion protein offers neuroprotection in astrocytes submitted to amyloid ß oligomer toxicity.

The cellular prion protein (PrPC), in its native conformation, performs numerous cellular and cognitive functions in brain tissue. However, despite the cellular prion research in recent years, there are still questions about its participation in oxidative and neurodegenerative processes. This study aims to elucidate the involvement of PrPC in the neuroprotection cascade in the presence of oxidative stressors. For that, astrocytes from wild-type mice and knockout to PrPC were subjected to the induction of oxidative stress with hydrogen peroxide (H2O2) and with the toxic oligomer of the amyloid ß protein (AßO). We observed that the presence of PrPC showed resistance in the cell viability of astrocytes. It was also possible to monitor changes in basic levels of metals and associate them with an induced damage condition, indicating the precise role of PrPC in metal homeostasis, where the absence of PrPC leads to metallic unbalance, culminating in cellular vulnerability to oxidative stress. Increased caspase 3, p-Tau, p53, and Bcl2 may establish a relationship between a PrPC and an induced damage condition. Complementarily, it has been shown that PrPC prevents the internalization of AßO and promotes its degradation under oxidative stress induction, thus preventing protein aggregation in astrocytes. It was also observed that the presence of PrPC can be related to translocating SOD1 to cell nuclei under oxidative stress, probably controlling DNA damage. The results of this study suggest that PrPC acts against oxidative stress activating the cellular response and defense by displaying neuroprotection to neurons and ensuring the functionality of astrocytes.

Exposure to Inorganic Arsenic in Rice in Brazil: A Human Health Risk Assessment.

In certain populations, rice is the main source of exposure to inorganic arsenic (iAs), which is associated with cancer and non-cancer effects. Although rice is a staple food in Brazil, there have been few studies about the health risks for the Brazilian population. The objective of this study was to assess the risks of exposure to iAs from white rice and brown rice in Brazil, in terms of the carcinogenic and non-carcinogenic effects, and to propose measures to mitigate those risks. The incremental lifetime cancer risk (ILCR) and hazard quotient (HQ) were calculated in a probabilistic framework. The mean ILCR was 1.5 × 10-4 for white rice and 6.0 × 10-6 for brown rice. The HQ for white and brown rice was under 1. The ILCR for white and brown rice was high, even though the iAs concentration in rice is below the maximum contaminant level. The risk for brown rice consumption was lower, which was not expected. Various mitigation measures discussed in this report are estimated to reduce the risk from rice consumption by 5-67%. With the support of public policies, measures to reduce these risks for the Brazilian population would have a positive impact on public health.

Soil Treatment with Nitric Oxide-Releasing Chitosan Nanoparticles Protects the Root System and Promotes the Growth of Soybean Plants under Copper Stress.

The nanoencapsulation of nitric oxide (NO) donors is an attractive technique to protect these molecules from rapid degradation, expanding, and enabling their use in agriculture. Here, we evaluated the effect of the soil application of chitosan nanoparticles containing S-nitroso-MSA (a S-nitrosothiol) on the protection of soybeans (Glycine max cv. BRS 257) against copper (Cu) stress. Soybeans were grown in a greenhouse in soil supplemented with 164 and 244 mg kg-1 Cu and treated with a free or nanoencapsulated NO donor at 1 mM, as well as with nanoparticles without NO. There were also soybean plants treated with distilled water and maintained in soil without Cu addition (control), and with Cu addition (water). The exogenous application of the nanoencapsulated and free S-nitroso-MSA improved the growth and promoted the maintenance of the photosynthetic activity in Cu-stressed plants. However, only the nanoencapsulated S-nitroso-MSA increased the bioavailability of NO in the roots, providing a more significant induction of the antioxidant activity, the attenuation of oxidative damage, and a greater capacity to mitigate the root nutritional imbalance triggered by Cu stress. The results suggest that the nanoencapsulation of the NO donors enables a more efficient delivery of NO for the protection of soybean plants under Cu stress.

Ready-to-use room temperature one-pot synthesis of surface-decorated gold nanoparticles with targeting attributes.

Gold nanoparticles (AuNPs) can be used in diagnostic and therapeutic applications. The development of facile and fast synthetic approaches is accordingly desirable towards ready-to-use biomedical materials. We report a practical one-pot method for the synthesis in aqueous media and room temperature of surface-decorated AuNPs with enhanced biological responses. The gold ions could be reduced using only polyethyleneimine (PEI) derivatives containing sugar and-or alkyl chains acting simultaneously as reducing and stabilizing agent, without the aid of any other mediator. The process is possibly potentialized by the presence of the amino groups in the polymer chains which further confer colloidal stability. The kinetics of AuNPs nucleation and growth depends on the chemical nature of the polymer chains. Particularly, the presence of lactose moieties conjugated to the PEI chains conducted to surface-decorated AuNPs with low cytotoxicity that are remarkably faster uptaken by HepG2 cells. These cells overexpress asialoglycoprotein (ASGP-R), a galactose receptor. These findings may kick off significant advances towards the practical and ready-to-use manufacturing of functionalized AuNPs towards cell-targeting since the methodology is applicable for a large variety of other ligands that can be conjugated to the same polymer chains.

Comparative Study on Lead and Copper Biosorption Using Three Bioproducts from Edible Mushrooms Residues.

Agricultural waste products can be used as biosorbents for bioremediation once they are low-cost and high-efficient in pollutants removal. Thus, waste products from mushroom farming such as cutting and substrate of Lentinula edodes (popularly known as shiitake) and Agaricus bisporus (also known as champignon) were evaluated as biosorbents for metallic contaminants copper (Cu) and lead (Pb). Shiitake and champignon stalks, and shiitake substrate (medium in which shiitake was cultivated) were dried, grounded, characterized and experimented to remove Cu and Pb from contaminated water. The Sips model was used to establish the adsorption isotherms. Regarding Cu, champignon stalks have the best removal efficiency (43%), followed by substrate and stalks of shiitake (37 and 30%, respectively). Pb removals were similar among three residues (from 72 to 83%), with the champignon stalks standing out. The maximum adsorption capacities (qmax) for Cu in shiitake and champignon stalks were 22.7 and 31.4 mg/g-1, respectively. For Pb, qmax for shiitake and champignon stalks, and shiitake substrate were 130.0, 87.0 and 84.0 mg/g-1, respectively. The surface morphology of the champignon stalks revealed an organized and continuous structure. After an interaction with metals, the stalk of champignon accumulated the metal ions into interstices. Mushroom residues showed a relevant adsorption efficiency, especially for Pb. Mushroom farming waste are a very low-cost and promising alternative for removing toxic heavy metals from aquatic environment.

Cellular prion protein activates Caspase 3 for apoptotic defense mechanism in astrocytes.

The cellular prion protein (PrPC) is anchored in the plasma membrane of cells, and it is highly present in cells of brain tissue, exerting numerous cellular and cognitive functions. The present study proves the importance of PrPC in the cellular defense mechanism and metal homeostasis in astrocytes cells. Through experimental studies using cell lines of immortalized mice astrocytes (wild type and knockout for PrPC), we showed that PrPc is involved in the apoptosis cell death process by the activation of Caspase 3, downregulation of p53, and cell cycle maintenance. Metal homeostasis was determined by inductively coupled plasma mass spectrometry technique, indicating the crucial role of PrPC to lower intracellular calcium. The lowered calcium concentration and the Caspase 3 downregulation in the PrPC-null astrocytes resulted in a faster growth rate in cells, comparing with PrPC wild-type one. The presence of PrPC shows to be essential to cell death and healthy growth. In conclusion, our results show for the first time that astrocyte knockout cells for the cellular prion protein could modulate apoptosis-dependent cell death pathways.

Isolation and characterization of bacteria from a brazilian gold mining area with a capacity of arsenic bioaccumulation.

In Paracatu, a city in Minas Gerais State (Brazil), the gold mineral extraction produces wastes that contribute to environmental contamination by arsenic. This work describes the evaluation of arsenic concentration from soil of a gold mining area in Paracatu and the selection of arsenic resistant bacteria. In the process of culturing enrichment, 38 bacterial strains were isolated and the minimum inhibitory concentration (MIC) was determined in solid medium for each strain. Three bacterial strains named P1C1Ib, P2Ic and P2IIB were resistant to 3000 mg L-1 of arsenite. Analysis of 16S rDNA gene sequences revealed that these bacteria belong to Bacillus cereus and Lysinibacillus boronitolerans species. After cultivation of the strains P1C1Ib, P2Ic and P2IIIb, 69.38%-71.88% of arsenite and 82.39%-85.72% of arsenate concentrations were reduced from the culture medium, suggesting the potential application of theses strains in bioremediation processes.

Evaluation of uptake, translocation, and accumulation of arsenic species by six different Brazilian rice (Oryza sativa L.) cultivars.

Rice is a significant source of arsenic (As) exposure. The accumulation of the plant depends on several factors, including environmental conditions and genetic factors. The differences in As uptake, translocation, and grains filling in different cultivars are a focus on studies to mitigate the grains contamination. This study assessed the pattern of As species accumulation in different Brazilian rice cultivars (Oryza sativa L.). Thus, pot experiments were conducted with 6 different cultivars (white rice: EPAGRI 109, EPAGRI 108, BRS Tiotaka SCS, and SCS 114 Andosan and red rice: Maranhão and Cáqui) cultivated in soils at low (As-) (0.65 mg kg-1) and high (As+) (12.1 mg kg-1) As levels. All cultivars in As+ group presented total As (t-As) in grains more elevated than the maximum limit of inorganic arsenic (i-As) recommended by Codex Alimentarius Commission. The As speciation disclose that Maranhão, Caqui, and SCS 114 Andosan cultivars presented the lowest % i-As (27%, 25% and 31%, respectively) at the highest As exposure condition. On the other hand, higher i-As concentration and % i-As (91%) were observed in EPAGRI 108. Moreover, EPAGRI 108 and EPAGRI 109 had the highest transference factor soil-to-grain (TFsoil-grain = 0.22 and 0.20, respectively). Interestingly, for the cultivars EPAGRI 108 and Maranhão, the levels of some essential elements (Co and Mn) in grains were modulated by the levels of As in the soil. This study shows that levels of i-As were modulated by the type of Brazilian rice cultivar, the range of As levels in soil, As phytotoxicity and the transference factor of As from soil to root straw and grains. Moreover, SCS 114 Andosan is the promising cultivar that exhibits low t-As and % i-As in grains and low TF soil-grain.

Flow of essential elements in subcellular fractions during oxidative stress.

Essential trace elements are commonly found in altered concentrations in the brains of patients with neurodegenerative diseases. Many studies in trace metal determination and quantification are conducted in tissue, cell culture or whole brain. In the present investigation, we determined by ICP-MS Fe, Cu, Zn, Ca, Se, Co, Cr, Mg, and Mn in organelles (mitochondria, nuclei) and whole motor neuron cell cultured in vitro. We performed experiments using two ways to access oxidative stress: cell treatments with H2O2 or Aß-42 peptide in its oligomeric form. Both treatments caused accumulation of markers of oxidative stress, such as oxidized proteins and lipids, and alteration in DNA. Regarding trace elements, cells treated with H2O2 showed higher levels of Zn and lower levels of Ca in nuclei when compared to control cells with no oxidative treatments. On the other hand, cells treated with Aß-42 peptide in its oligomeric form showed higher levels of Mg, Ca, Fe and Zn in nuclei when compared to control cells. These differences showed that metal flux in cell organelles during an intrinsic external oxidative condition (H2O2 treatment) are different from an intrinsic external neurodegenerative treatment.

Toxic and essential elements in Nigerian rice and estimation of dietary intake through rice consumption.

In this study, levels and estimated daily intake (EDI) of two toxic elements, Cd and Pb, and eight essential elements: Ca, P, Zn, Mn, Co, Cu, Se and Mo, were determined in Nigerian rice samples. The mean levels of Cd, Pb and Co were 5.43±0.88, 38.66±5.42, 25.8±3.18 ng/g. The mean levels of Ca, P, Zn, Mn, Cu, Se and Mo were 71.5±7.31, 951±52.0, 10.2±0.63, 8.5±0.47, 3.07±0.18, 40.1±9.2 and 0.39±0.05 µg/g, respectively. The percentage contribution to the reference values for each element was 0.54, 7.71, 0.38, 9.51, 8.97, 31.3, 30.7, 5.1 and 60.7% for Cd, Pb, Ca, P, Zn, Mn, Cu, Se and Mo, respectively. The elemental nutrient levels in Nigerian rice samples are comparable to those obtained from other regions and their consumption does not pose any serious health risk to consumers.

Arsenic biotransformation by cyanobacteria from mining areas: evidences from culture experiments.

Elucidating the role of cyanobacteria in the biotransformation of arsenic (As) oxyanions is crucial to understand the biogeochemical cycle of this element and indicate species with potential for its bioremediation. In this study, we determined the EC50 for As(III) and As(V) and evaluated the biotransformation of As by Synechococcus sp. through high-performance liquid chromatography hyphenated to inductively coupled plasma mass spectrometry (HPLC-ICP-MS) and X-ray absorption fine structure spectroscopy (XAFS). Synechococcus sp. exhibited higher sensitivity to As(III) with an EC(50, 96 h) of 6.64 mg L(-1) that was approximately 400-fold lower than that for As(V). Even though the cells were exposed to concentrations of As(III) (6 mg L(-1)) approximately 67-fold lower than those of As(V) (400 mg L(-1)), similar intracellular concentrations of As (60.0 µg g(-1)) were observed after 30 days. As(V) was the predominant intracellular As species followed by As(III). Furthermore, organic As species such as monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) were observed in higher proportions after exposure to As(III). The differential toxicity among As oxyanions indicates that determining the redox state of As in the environment is fundamental to estimate toxicity risks to aquatic organisms. Synechococcus sp. demonstrated potential for its application in bioremediation due to the high accumulation of As and production of As organic compounds notably after exposure to As(III).

A simple and practical control of the authenticity of organic sugarcane samples based on the use of machine-learning algorithms and trace elements determination by inductively coupled plasma mass spectrometry.

A practical and easy control of the authenticity of organic sugarcane samples based on the use of machine-learning algorithms and trace elements determination by inductively coupled plasma mass spectrometry is proposed. Reference ranges for 32 chemical elements in 22 samples of sugarcane (13 organic and 9 non organic) were established and then two algorithms, Naive Bayes (NB) and Random Forest (RF), were evaluated to classify the samples. Accurate results (>90%) were obtained when using all variables (i.e., 32 elements). However, accuracy was improved (95.4% for NB) when only eight minerals (Rb, U, Al, Sr, Dy, Nb, Ta, Mo), chosen by a feature selection algorithm, were employed. Thus, the use of a fingerprint based on trace element levels associated with classification machine learning algorithms may be used as a simple alternative for authenticity evaluation of organic sugarcane samples.

Blood thioredoxin reductase activity, oxidative stress and hematological parameters in painters and battery workers: relationship with lead and cadmium levels in blood.

Oxidative stress has been shown to be involved in lead and cadmium toxicity. We recently showed that the activity of the antioxidant enzyme thioredoxin reductase (TrxR) is increased in the kidneys of lead-exposed rats. The present study evaluated the blood cadmium and blood lead levels (BLLs) and their relationship with hematological and oxidative stress parameters, including blood TrxR activity in 50 painters, 23 battery workers and 36 control subjects. Erythrocyte δ-aminolevulinate dehydratase (δ-ALA-D) activity and its reactivation index were measured as biomarkers of lead effects. BLLs increased in painters, but were even higher in the battery workers group. In turn, blood cadmium levels increased only in the painters group, whose levels were higher than the recommended limit. δ-ALA-D activity was inhibited only in battery workers, whereas the δ-ALA-D reactivation index increased in both exposed groups; both parameters were correlated to BLLs (r = -0.59 and 0.84, P < 0.05), whereas the reactivation index was also correlated to blood cadmium levels (r = 0.27, P < 0.05). The changes in oxidative stress and hematological parameters were distinctively associated with either BLLs or blood cadmium levels, except glutathione-S-transferase activity, which was correlated with both lead (r = 0.34) and cadmium (r = 0.47; P < 0.05). However, TrxR activity did not correlate with any of the metals evaluated. In conclusion, blood TrxR activity does not seem to be a good parameter to evaluate oxidative stress in lead- and cadmium-exposed populations. However, lead-associated changes in biochemical and hematological parameters at low BLLs underlie the necessity of re-evaluating the recommended health-based limits in occupational exposure to this metal.

Speciation of arsenic in rice and estimation of daily intake of different arsenic species by Brazilians through rice consumption.

Rice is an important source of essential elements. However, rice may also contain toxic elements such as arsenic. Therefore, in the present study, the concentration of total arsenic and five main chemical species of arsenic (As(3+), As(5+), DMA, MMA and AsB) were evaluated in 44 different rice samples (white, parboiled white, brown, parboiled brown, parboiled organic and organic white) from different Brazilian regions using high-performance liquid chromatography hyphenated to inductively coupled plasma mass spectrometry (HPLC-ICP-MS). The mean level of total arsenic was 222.8 ng g(-1) and the daily intake of inorganic arsenic (the most toxic form) from rice consumption was estimated as 10% of the Provisional Tolerable Daily Intake (PTDI) with a daily ingestion of 88 g of rice. Inorganic arsenic (As(3+), As(5+)) and dimethylarsinic acid (DMA) are the predominant forms in all samples. The percentages of species were 38.7; 39.7; 3.7 and 17.8% for DMA, As(3+), MMA and As(5+), respectively. Moreover, rice samples harvested in the state of Rio Grande do Sul presented more fractions of inorganic arsenic than rice in Minas Gerais or Goiás, which could lead to different risks of arsenic exposure.

A simple method based on ICP-MS for estimation of background levels of arsenic, cadmium, copper, manganese, nickel, lead, and selenium in blood of the Brazilian population.

Throughout the world, biomonitoring has become the standard for assessing exposure of individuals to toxic elements as well as for responding to serious environmental public health problems. However, extensive biomonitoring surveys require rapid and simple analytical methods. Thus, a simple and high-throughput method is proposed for the determination of arsenic (As), cadmium (Cd), copper (Cu), manganese (Mn), nickel (Ni), lead (Pb), and selenium (Se) in blood samples by using inductively coupled plasma-mass spectrometry (ICP-MS). Prior to analysis, 200 microl of blood samples was mixed with 500 microl of 10% v/v tetramethylammonium hydroxide (TMAH) solution, incubated for 10 min, and subsequently diluted to 10 ml with a solution containing 0.05% w/v ethylenediamine tetraacetic acid (EDTA) + 0.005% v/v Triton X-100. After that, samples were directly analyzed by ICP-MS (ELAN DRC II). Rhodium was selected as an internal standard with matrix-matching calibration. Method detection limits were 0.08, 0.04, 0.5, 0.09, 0.12, 0.04, and 0.1 microg//L for As, Cd, Cu, Mn, Ni, Pb, and Se, respectively. Validation data are provided based on the analysis of blood samples from the trace elements inter-\comparison program operated by the Institut National de Sante Publique du Quebec, Canada. Additional validation was provided by the analysis of human blood samples by the proposed method and by using electrothermal atomic absorption spectrometry (ETAAS). The method was subsequently applied for the estimation of background metal blood values in the Brazilian population. In general, the mean concentrations of As, Cd, Cu, Mn, Ni, Pb, and Se in blood were 1.1, 0.4, 890, 9.6, 2.1, 65.4, and 89.3 microg/L, respectively, and are in agreement with other global populations. Influences of age, gender, smoking habits, alcohol consumption, and geographical variation on the values were also considered. Smoking habits influenced the levels of Cd in blood. The levels of Cu, Mn, and Pb were significantly correlated with gender, whereas Cu and Pb were significantly correlated with age. There were also interesting differences in Mn and Se levels in the population living in the north of Brazil compared to the south.

Identification and distribution of mercury species in rat tissues following administration of thimerosal or methylmercury.

Methylmercury (Met-Hg) is one the most toxic forms of Hg, with a considerable range of harmful effects on humans. Sodium ethyl mercury thiosalicylate, thimerosal (TM) is an ethylmercury (Et-Hg)-containing preservative that has been used in manufacturing vaccines in many countries. Whereas the behavior of Met-Hg in humans is relatively well known, that of ethylmercury (Et-Hg) is poorly understood. The present study describes the distribution of mercury as (-methyl, -ethyl and inorganic mercury) in rat tissues (brain, heart, kidney and liver) and blood following administration of TM or Met-Hg. Animals received one dose/day of Met-Hg or TM by gavage (0.5 mg Hg/kg). Blood samples were collected after 6, 12, 24, 48, 96 and 120 h of exposure. After 5 days, the animals were killed, and their tissues were collected. Total blood mercury (THg) levels were determined by ICP-MS, and methylmercury (Met-Hg), ethylmercury (Et-Hg) and inorganic mercury (Ino-Hg) levels were determined by speciation analysis with LC-ICP-MS. Mercury remains longer in the blood of rats treated with Met-Hg compared to that of TM-exposed rats. Moreover, after 48 h of the TM treatment, most of the Hg found in blood was inorganic. Of the total mercury found in the brain after TM exposure, 63% was in the form of Ino-Hg, with 13.5% as Et-Hg and 23.7% as Met-Hg. In general, mercury in tissues and blood following TM treatment was predominantly found as Ino-Hg, but a considerable amount of Et-Hg was also found in the liver and brain. Taken together, our data demonstrated that the toxicokinetics of TM is completely different from that of Met-Hg. Thus, Met-Hg is not an appropriate reference for assessing the risk from exposure to TM-derived Hg. It also adds new data for further studies in the evaluation of TM toxicity.

Evaluation of the use of human hair for biomonitoring the deficiency of essential and exposure to toxic elements.

Monitoring the nutritional status of essential elements and assessing exposure of individuals to toxic elements is of great importance for human health. Thus, the appropriate selection and measurement of biomarkers of internal dose is of critical importance. Due to their many advantages, hair samples have been widely used to assess human exposure to different contaminants. However, the validity of this biomarker in evaluating the level of trace elements in the human body is debatable. In the present study, we evaluated the relationship between levels of trace elements in hair and whole blood or plasma in a Brazilian population. Hair, blood and plasma were collected from 280 adult volunteers for metal determination. An ICP-MS was used for sample analysis. Manganese, copper, lead and strontium levels in blood varied from 5.1 to 14.7, from 494.8 to 2383.8, from 5.9 to 330.1 and from 11.6 to 87.3 microg/L, respectively. Corresponding levels in hair varied from 0.05 to 6.71, from 0.02 to 37.59, from 0.02 to 30.63 and from 0.9 to 12.6 microg/g. Trace element levels in plasma varied from 0.07 to 8.62, from 118.2 to 1577.7 and from 2.31 to 34.2 microg/L for Mn, Cu and Sr, respectively. There was a weak correlation (r=0.22, p<0.001) between lead levels in hair and blood. Moreover, copper and strontium levels in blood correlate with those levels in plasma (r=0.64 , p<0.001 for Cu) and (r=0.22, p<0.05 for Sr). However, for Cu, Mn and Sr there was no correlation between levels in hair and blood. Our findings suggest that while the idea of measuring trace elements in hair is attractive, hair is not an appropriate biomarker for evaluating Cu, Mn and Sr deficiency or Pb exposure.