Assessing the toxicity of one-step-synthesized PEG-coated gold nanoparticles: in vitro and in vivo studies.

OBJECTIVE: To evaluate the in vitro and in vivo toxicities of polyethylene glycol-coated gold nanoparticles synthesized using a one-step process. METHODS: Gold nanoparticles were prepared via a co-precipitation method using polyethylene glycol, and the synthesis product was characterized. For the in vitro evaluation, a flow cytometry analysis with Annexin V and iodide propidium staining was used to assess cytotoxicity in MG-63 cells labeled with 10, 50, and 100µg/mL of nanoparticle concentration. For the in vivo evaluation, nanoparticles were administered intraperitoneally at a dose of 10mg/kg dose in 10-week-old mice. Toxicity was assessed 24 hours and 7 days after administration via histopathological analysis of various tissues, as well as through renal, hepatic, and hematopoietic evaluations. RESULTS: Synthesized nanoparticles exhibited different hydrodynamic sizes depending on the medium: 51.27±1.62nm in water and 268.12±28.45nm (0 hour) in culture medium. They demonstrated a maximum absorbance at 520nm and a zeta potential of -8.419mV. Cellular viability exceeded 90%, with less than 3% early apoptosis, 6% late apoptosis, and 1% necrosis across all labeling conditions, indicating minimal cytotoxicity differences. Histopathological analysis highlighted the accumulation of nanoparticles in the mesentery; however, no lesions or visible agglomeration was observed in the remaining tissues. Renal, hepatic, and hematopoietic analyses showed no significant differences at any time point. CONCLUSION: Polyethylene glycol-coated gold nanoparticles exhibit extremely low toxicity and high biocompatibility, showing promise for future studies.

Gold nanoparticle intratesticular injections as a potential animal sterilization tool: Long-term reproductive and toxicological implications.

This study aimed to evaluate the gold nanoparticles (AuNPs) animal sterilizing potential after intratesticular injections and long-term adverse reproductive and systemic effects. Adult male Wistar rats were divided into control and gold nanoparticle (AuNPs) groups. The rats received 200 µL of saline or AuNPs solution (16 µg/mL) on experimental days 1 and 7 (ED1 and ED7). After 150 days, the testicular blood flow was measured, and the rats were mated with females. After mating, male animals were euthanized for histological, cellular, and molecular evaluations. The female fertility indices and fetal development were also recorded. The results indicated increased blood flow in the testes of treated animals. Testes from treated rats had histological abnormalities, shorter seminiferous epithelia, and oxidative stress. Although the sperm concentration was lower in the AuNP-treated rats, there were no alterations in sperm morphology. Animals exposed to AuNPs had decreased male fertility indices, and their offspring had lighter and less efficient placentas. Additionally, the anogenital distance was longer in female fetuses. There were no changes in the histology of the kidney and liver, the lipid profile, and the serum levels of LH, testosterone, AST, ALT, ALP, albumin, and creatinine. The primary systemic effect was an increase in MDA levels in the liver and kidney, with only the liver experiencing an increase in CAT activity. In conclusion, AuNPs have a long-term impact on reproduction with very slight alterations in animal health. The development of reproductive biotechnologies that eliminate germ cells or treat local cancers can benefit from using AuNPs.

Genotoxicity and mutagenicity in blood and drinking water induced by arsenic in an impacted gold mining region in Colombia.

Arsenic (As) is one of the most dangerous substances that can affect human health and long-term exposure to As in drinking water can even cause cancer. The objective of this study was to investigate the concentrations of total As in the blood of inhabitants of a Colombian region impacted by gold mining and to evaluate its genotoxic effect through DNA damage by means of the comet assay. Additionally, the concentration of As in the water consumed by the population as well as the mutagenic activity of drinking water (n = 34) in individuals were determined by hydride generator atomic absorption spectrometry and the Ames test, respectively. In the monitoring, the study population was made up of a group of 112 people, including inhabitants of four municipalities: Guaranda, Sucre, Majagual, and San Marcos from the Mojana region as the exposed group, and Montería as a control group. The results showed DNA damage related to the presence of As in blood (p < 0.05) in the exposed population, and blood As concentrations were above the maximum allowable limit of 1 µg/L established by the ATSDR. A mutagenic activity of the drinking water was observed, and regarding the concentrations of As in water, only one sample exceeded the maximum permissible value of 10 µg/L established by the WHO. The intake of water and/or food containing As is potentially generating DNA damage in the inhabitants of the Mojana region, which requires surveillance and control by health entities to mitigate these effects.

The aspect ratio of gold nanorods as a cytotoxicity factor on Raphidocelis subcaptata.

Gold nanorods (AuNRs) are promising nanoscale materials for several technological and biomedical applications. The physicochemical properties of AuNRs, including size, shape and surface features, are crucial factors affecting their cytotoxicity. In this study, we investigated the effects of different aspect ratios of AuNRs (1.90, 2.35, 3.25 and 3.50) at concentrations of 2 and 10 µg mL-1 on their cytotoxicity and cellular uptake in green algae Raphidocelis subcaptata. The experiment was performed in oligotrophic freshwater medium in a growth chamber with constant agitation of 80 rpm under controlled conditions (120 µEm-2s-1 illumination; 12:12h light dark cycle and constant temperature of 22 ± 2 °C). The algal growth was monitored daily for 96 h via electronic absorbance scanning at 600-750 nm. Oxidative stress, cell viability and autofluorescence were evaluated using a flow cytometer. Oxidative stress quantified by loading cultures with the fluorescent dye 2', 7'-dichlorofluorescein diacetate. To assess algal cell viability, propidium iodide was selected as the fluorescent probe. Our results indicated that the aspect ratio of AuNRs mediates their biological effects in green algae R. subcaptata. A positive correlation between oxidative stress and increase of aspect ratio was found at concentration of 10 µg mL-1. Higher cytotoxicity and mortality were observed for algae incubated with higher aspect ratios AuNRs (3.50). These findings may be useful to understand the impact of the AuNRs in aquatic environments, contributing to ecosystem management and nanomaterials regulation.

Malignancy and tumorigenicity of melanoma B16 cells are not affected by silver and gold nanoparticles.

Gold (AuNP) and silver (AgNP) nanoparticles have been incorporated into many therapeutic and diagnostic applications. However, previous studies revealed toxic properties as well as the hormesis phenomenon of many nanoparticles in different biological models. To evaluate the effects of low concentrations of AuNP and AgNP on murine melanoma cells B16F1 and B16F10 and relate them with phenotype changes, cells were exposed for 24 and 48 h. No cytotoxicity was observed for B16 cells through neutral red, MTT, trypan blue, and crystal violet assays at concentrations from 0.01 to 10 ng mL-1. Likewise, the nanoparticles did not interfere with drug-efflux activity, cell migration, cell cycle, and colony formation. Slight toxicity was observed for B16F10 exposed to 100 ng mL-1, with a decreased number of viable and attached cells, indicating differential sensitivity of B16F1 and B16F10 cells to the nanoparticles. Furthermore, colony size dispersion decreased for both B16 cell sub-lines. Therefore, there is no evidence that the tested concentrations of AuNP and AgNP can render B16 cells more aggressive and malignant, which is important since both nanoparticles are already largely used in nanotechnological products. Considering studies that have showed the hormesis effect of nanoparticles at low concentrations, which could protect cancer cells against chemotherapy, further investigation is advised.

Understanding gold toxicity in aerobically-grown Escherichia coli.

BACKGROUND: There is an emerging field to put into practice new strategies for developing molecules with antimicrobial properties. In this line, several metals and metalloids are currently being used for these purposes, although their cellular effect(s) or target(s) in a particular organism are still unknown. Here we aimed to investigate and analyze Au3+ toxicity through a combination of biochemical and molecular approaches. RESULTS: We found that Au3+ triggers a major oxidative unbalance in Escherichia coli, characterized by decreased intracellular thiol levels, increased superoxide concentration, as well as by an augmented production of the antioxidant enzymes superoxide dismutase and catalase. Because ROS production is, in some cases, associated with metal reduction and the concomitant generation of gold-containing nanostructures (AuNS), this possibility was evaluated in vivo and in vitro. CONCLUSIONS: Au3+ is toxic for E. coli because it triggers an unbalance of the bacterium's oxidative status. This was demonstrated by using oxidative stress dyes and antioxidant chemicals as well as gene reporters, RSH concentrations and AuNS generation.

Understanding gold toxicity in aerobically-grown Escherichia coli

BACKGROUND: There Is an emerging field to put Into practice new strategies for developing molecules with antimicrobial properties. In this line, several metals and metalloids are currently being used for these purposes, although their cellular effect(s) or target(s) in a particular organism are still unknown. Here we aimed to investigate and analyze Au3+ toxicity through a combination of biochemical and molecular approaches. RESULTS: We found that Au3+ triggers a major oxidative unbalance in Escherichia coli, characterized by decreased intracellular thiol levels, increased superoxide concentration, as well as by an augmented production of the antioxidant enzymes superoxide dismutase and catalase. Because ROS production is, in some cases, associated with metal reduction and the concomitant generation of gold-containing nanostructures (AuNS), this possibility was evaluated in vivo and in vitro. CONCLUSIONS: Au3+ is toxic for E. coli because it triggers an unbalance of the bacterium's oxidative status. This was demonstrated by using oxidative stress dyes and antioxidant chemicals as well as gene reporters, RSH concentrations and AuNS generation.

Suitability of 3D human brain spheroid models to distinguish toxic effects of gold and poly-lactic acid nanoparticles to assess biocompatibility for brain drug delivery.

BACKGROUND: The blood brain barrier (BBB) is the bottleneck of brain-targeted drug development. Due to their physico-chemical properties, nanoparticles (NP) can cross the BBB and accumulate in different areas of the central nervous system (CNS), thus are potential tools to carry drugs and treat brain disorders. In vitro systems and animal models have demonstrated that some NP types promote neurotoxic effects such as neuroinflammation and neurodegeneration in the CNS. Thus, risk assessment of the NP is required, but current 2D cell cultures fail to mimic complex in vivo cellular interactions, while animal models do not necessarily reflect human effects due to physiological and species differences. RESULTS: We evaluated the suitability of in vitro models that mimic the human CNS physiology, studying the effects of metallic gold NP (AuNP) functionalized with sodium citrate (Au-SC), or polyethylene glycol (Au-PEG), and polymeric polylactic acid NP (PLA-NP). Two different 3D neural models were used (i) human dopaminergic neurons differentiated from the LUHMES cell line (3D LUHMES) and (ii) human iPSC-derived brain spheroids (BrainSpheres). We evaluated NP uptake, mitochondrial membrane potential, viability, morphology, secretion of cytokines, chemokines and growth factors, and expression of genes related to ROS regulation after 24 and 72 h exposures. NP were efficiently taken up by spheroids, especially when PEGylated and in presence of glia. AuNP, especially PEGylated AuNP, effected mitochondria and anti-oxidative defense. PLA-NP were slightly cytotoxic to 3D LUHMES with no effects to BrainSpheres. CONCLUSIONS: 3D brain models, both monocellular and multicellular are useful in studying NP neurotoxicity and can help identify how specific cell types of CNS are affected by NP.

Evaluation of gold nanorods toxicity on isolated mitochondria.

Gold nanorods (AuNRs) have been studied extensively in biomedicine due to their biocompatibility and their unique properties. Some studies reported that AuNRs selectively accumulate on cancer cell mitochondria causing its death. However, the immediate effects of this accumulation needed further investigations. In this context, we evaluated the effect of AuNRs on the mitochondrial integrity of isolated rat liver mitochondria. We verified that AuNRs decreased the mitochondrial respiratory ratio by decreasing the phosphorylation and maximal states. Additionally, AuNRs caused a decrease in the production of mitochondrial ROS and a delay in mitochondrial swelling. Moreover, even with cyclosporine A treatment, AuNRs disrupted the mitochondrial potential. With the highest concentration of AuNRs studied, disorganized mitochondrial crests and intermembrane separation were observed in TEM images. These results indicate that AuNRs can interact with mitochondria, disrupting the electron transport chain. This study provides new evidence of the immediate effects of AuNRs on mitochondrial bioenergetics.

Biosynthesis of gold nanoparticles by two bacterial and fungal strains, Bacillus cereus and Fusarium oxysporum, and assessment and comparison of their nanotoxicity in vitro by direct and indirect assays

Background: Although nanoparticles (NPs) have many advantages, it has been proved that they may be absorbed by and have toxic effects on the human body. Recent research has tried to evaluate and compare the nanotoxicity of gold nanoparticles (AuNPs) produced by two types of microorganisms in vitro by two different methods. AuNPs were produced by Bacillus cereus and Fusarium oxysporum, and their production was confirmed by visible spectral, transmission electron microscope, and X-ray diffraction (XRD) analyses. The human fibroblast cell line CIRC-HLF was treated with AuNPs, and the induced nanotoxicity was measured using direct microscopic and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Results: The results showed that the produced AuNPs had a maximum absorbance peak around 510­530 nanometer (nm), with spherical, hexagonal, and octagonal shapes and average sizes around 20­50 nm. The XRD results confirmed the presence of GNPs in the microbial culture supernatants. An MTT assay showed that GNPs had dose-dependent toxic effects, and microscopic analysis showed that GNPs induced cell abnormalities in doses lower than the determined half-maximal inhibitory concentrations (IC50s). Conclusions: In conclusion, the biologically produced AuNPs had toxic effects in the cell culture, and direct techniques such as microscopic evaluation instead of indirect methods such as MTT assay were more useful for assessing the nanotoxicity of the biologically produced AuNPs. Thus, the use of only MTT assay for nanotoxicity evaluation of AuNPs is not desirable.

Biological response of HeLa cells to gold nanoparticles coated with organic molecules.

In this work, gold nanospheres functionalized with low weight organic molecules (4-aminothiphenol and cysteamine) were synthesized in a one-step method for their in vitro cytotoxic evaluation on HeLa cells. To enhance the biocompatibility of the cysteamine-capped GNPs, BSA was used due to its broad PH stability and high binding affinity to gold nanoparticles. Besides, the widely reported silica coated gold nanorods were tested here to contrast their toxic response against our nanoparticles coated with organic molecules. Our results shown, the viability measured at 1.9×10-5M did not show significant differences against negative controls for all the samples; however, the metabolic activity of HeLa cells dropped when they were exposed to silica gold nanorods in the range of concentrations from 2.9×10-7M to 3.0×10-4M, while in the cases of gold nanospheres, we found that only at concentrations below 1.9×10-5M metabolic activity was normal. Our preliminary results did not indicate any perceivable harmful toxicity to cell membrane, cytoskeleton or nucleus due to our nanospheres at 1.9×10-5M. Additional test should be conducted in order to ensure a safe use of them for biological applications, and to determine the extent of possible damage.

Gold nanoparticles alter parameters of oxidative stress and energy metabolism in organs of adult rats.

This study evaluated the parameters of oxidative stress and energy metabolism after the acute and long-term administration of gold nanoparticles (GNPs, 10 and 30 nm in diameter) in different organs of rats. Adult male Wistar rats received a single intraperitoneal injection or repeated injections (once daily for 28 days) of saline solution, GNPs-10 or GNPs-30. Twenty-four hours after the last administration, the animals were killed, and the liver, kidney, and heart were isolated for biochemical analysis. We demonstrated that acute administration of GNPs-30 increased the TBARS levels, and that GNPs-10 increased the carbonyl protein levels. The long-term administration of GNPs-10 increased the TBARS levels, and the carbonyl protein levels were increased by GNPs-30. Acute administration of GNPs-10 and GNPs-30 increased SOD activity. Long-term administration of GNPs-30 increased SOD activity. Acute administration of GNPs-10 decreased the activity of CAT, whereas long-term administration of GNP-10 and GNP-30 altered CAT activity randomly. Our results also demonstrated that acute GNPs-30 administration decreased energy metabolism, especially in the liver and heart. Long-term GNPs-10 administration increased energy metabolism in the liver and decreased energy metabolism in the kidney and heart, whereas long-term GNPs-30 administration increased energy metabolism in the heart. The results of our study are consistent with other studies conducted in our research group and reinforce the fact that GNPs can lead to oxidative damage, which is responsible for DNA damage and alterations in energy metabolism.

Peptides and proteins used to enhance gold nanoparticle delivery to the brain: preclinical approaches.

An exciting and emerging field in nanomedicine involves the use of gold nanoparticles (AuNPs) in the preclinical development of new strategies for the treatment and diagnosis of brain-related diseases such as neurodegeneration and cerebral tumors. The treatment of many brain-related disorders with AuNPs, which possess useful physical properties, is limited by the blood-brain barrier (BBB). The BBB highly regulates the substances that can permeate into the brain. Peptides and proteins may represent promising tools to improve the delivery of AuNPs to the central nervous system (CNS). In this review, we summarize the potential applications of AuNPs to CNS disorders, discuss different strategies based on the use of peptides or proteins to improve the delivery of AuNPs to the brain, and examine the intranasal administration route, which bypasses the BBB. We also analyze the potential neurotoxicity of AuNPs and the perspectives and new challenges concerning the use of peptides and proteins to enhance the delivery of AuNPs to the brain. The majority of the work described in this review is in a preclinical stage of experimentation, or in select cases, in clinical trials in humans. We note that the use of AuNPs still requires substantial study before being translated into human applications. However, for further clinical research, the issues related to the potential use of AuNPs must be analyzed.

Acute and chronic administration of gold nanoparticles cause DNA damage in the cerebral cortex of adult rats.

The use of gold nanoparticles is increasing in medicine; however, their toxic effects remain to be elucidated. Studies show that gold nanoparticles can cross the blood-brain barrier, as well as accumulate in the brain. Therefore, this study was undertaken to better understand the effects of gold nanoparticles on rat brains. DNA damage parameters were evaluated in the cerebral cortex of adult rats submitted to acute and chronic administration of gold nanoparticles of two different diameters: 10 and 30nm. During acute administration, adult rats received a single intraperitoneal injection of either gold nanoparticles or saline solution. During chronic administration, adult rats received a daily single injection for 28 days of the same gold nanoparticles or saline solution. Twenty-four hours after either single (acute) or last injection (chronic), the rats were euthanized by decapitation, their brains removed, and the cerebral cortices isolated for evaluation of DNA damage parameters. Our study showed that acute administration of gold nanoparticles in adult rats presented higher levels of damage frequency and damage index in their DNA compared to the control group. It was also observed that gold nanoparticles of 30nm presented higher levels of damage frequency and damage index in the DNA compared to the 10nm ones. When comparing the effects of chronic administration of gold nanoparticles of 10 and 30nm, we observed that occurred significant different index and frequency damage, comparing with control group. However, there is no difference between the 10 and 30nm groups in the levels of DNA damage for both parameters of the Comet assay. Results suggest that gold nanoparticles for both sizes cause DNA damage for chronic as well as acute treatments, although a higher damage was observed for the chronic one.

Nanopartículas de oro: aplicaciones y citotoxicidad in vitro / Gold nanoparticles: Applications and in vitro cytotoxicity

En los últimos años, la evolución en el desarrollo de productos elaborados a partir de nanotecnología ha experimentado un espectacular crecimiento. En particular, las nanopartículas de oro han despertado gran interés en los sectores biomédico y alimentario, donde se ha descrito su utilización en el tratamiento frente al cáncer o como parte integrante de envases resistentes a la abrasión, con propiedades antimicrobianas. Por tanto, se cree que la exposición humana a las nanopartículas de oro aumentará considerablemente en los próximos años, pudiendo tener esto repercusiones sobre la salud. En este marco, el estudio de la toxicología de las nanopartículas ha revelado que su toxicidad depende de multitud de factores. Además, en la bibliografía hay cierta controversia en torno a los posibles efectos citotóxicos inducidos por las nanopartículas de oro. Diversos estudios de exposición in vitro han destacado su inocuidad en algunas líneas celulares, mientras que otros trabajos demostraron respuesta citotóxica. La siguiente revisión tiene por objeto describir las propiedades más relevantes de las nanopartículas de oro considerando sus potenciales aplicaciones en medicina y en la industria de los alimentos, así como examinar su posible toxicidad, con especial énfasis en los estudios de citotoxicidad in vitro disponibles hasta el momento.

In the recent years, the development of nanotechnology-based products has experienced a spectacular growth. Especially, gold nanoparticles have awoken a great interest in the biomedical and food sector, where their applications in cancer treatment as well as their incorporation in abrasion resistant and antimicrobial packaging have been described. Therefore, it is believed that human exposure to gold nanoparticles will increase considerably in the next few years, which may arise possible human health hazards. Hence, toxicology studies on nanoparticles revealed that their toxicity depends on various factors. Furthermore, there is some controversy regarding to gold nanoparticle-induced cytotoxicity. Several in vitro studies have reported that gold nanoparticles are innocuous, while some investigations have demonstrated a cytotoxic response after the exposure to these. The aim of this review is to describe the most relevant properties of gold nanoparticles according to their possible applications in medicine and in food industry, as well as to provide information about their possible toxic effects, taking into account the cytotoxic in vitro studies published at present.

Cyto and genotoxicity of gold nanoparticles in human hepatocellular carcinoma and peripheral blood mononuclear cells.

Engineered nanomaterials have been extensively applied as active materials for technological applications. Since the impact of these nanomaterials on health and environment remains undefined, research on their possible toxic effects has attracted considerable attention. It is known that in humans, for example, the primary site of gold nanoparticles (AuNps) accumulation is the liver. The latter has motivated research regarding the use of AuNps for cancer therapy, since specific organs can be target upon appropriate functionalization of specific nanoparticles. In this study, we investigate the geno and cytotoxicity of two types of AuNps against human hepatocellular carcinoma cells (HepG2) and peripheral blood mononuclear cells (PBMC) from healthy human volunteers. The cells were incubated in the presence of different concentrations of AuNps capped with either sodium citrate or polyamidoamine dendrimers (PAMAM). Our results suggest that both types of AuNps interact with HepG2 cells and PBMC and may exhibit in vitro geno and cytotoxicity even at very low concentrations. In addition, the PBMC were less sensitive to DNA damage toxicity effects than cancer HepG2 cells upon exposure to AuNps.

Evaluation of central auditory processing in adolescents exposed to metallic mercury.

BACKGROUND: central auditory processing and exposure to metallic mercury. AIM: to evaluate the performance on tests of central auditory processing in adolescents exposed to metallic mercury. METHOD: participants were 52 adolescents, of both genders, who presented hearing thresholds within normal limits. The study group (SG) was composed by 21 adolescents who worked on the burning of gold-mercury amalgams, on the re-burning of gold in stores that sell this metal or who lived next to gold mines or gold shops. The control group (CG) was composed by 31 adolescents who had no history of exposure to mercury. Investigation procedures included the application of a clinical, occupational and mercury exposure history questionnaire, basic audiometric assessment as well as central auditory processing tests. RESULTS: Statistical significant differences in the auditory processing tests of non-verbal sound sequence memory test (p = 0,001), frequency pattern test (p = 0,000), duration pattern test (p = 0,000) and SSW test in Portuguese (p = 0,006) were observed between SG and CG. CONCLUSION: adolescents exposed to metallic mercury presented a lower performance on most of the auditory processing tests when compared to those who had no history of exposure to mercury. The main deficit found in the study was related to difficulty in distinguishing successive brief sounds.

Avaliação do processamento auditivo central em adolescentes expostos ao mercúrio metálico / Evaluation of central auditory processing in adolescents exposed to metallic mercury

TEMA: processamento auditivo central e exposição ao mercúrio metálico. OBJETIVO: comparar o desempenho nos testes comportamentais de processamento auditivo central entre adolescentes expostos e não expostos ao mercúrio metálico. MÉTODO: foram avaliados 52 adolescentes de ambos os sexos que apresentavam limiares auditivos dentro dos padrões de normalidade. O grupo de estudo (GE) incluiu 21 adolescentes que referiram trabalhar na queima dos amálgamas de ouro-mercúrio, re-queimar ouro em lojas que comercializam este metal ou residir próximos às áreas de garimpos e às lojas que comercializam ouro. O grupo de comparação (GC) foi composto por 31 adolescentes que não apresentaram história de exposição ao mercúrio. Os procedimentos incluíram um questionário sobre a história clínica, laboral e da exposição ao mercúrio, audiometria tonal liminar e bateria de testes para avaliação do processamento auditivo central. RESULTADOS: As diferenças de desempenho na avaliação do processamento auditivo central entre o GE e o GC foram estatisticamente significantes para o teste de memória seqüencial para sons não verbais (p = 0,001), para os testes de padrão de freqüência (p = 0,000) e de duração (p = 0,000) e para o SSW em Português (p = 0,006). CONCLUSÃO: os adolescentes expostos ao mercúrio metálico apresentaram desempenho significativamente inferior aos não expostos para a maioria dos testes comportamentais do processamento auditivo central e a principal alteração encontrada nessa população foi no processamento de sons breves e sucessivos.

BACKGROUND: central auditory processing and exposure to metallic mercury. AIM: to evaluate the performance on tests of central auditory processing in adolescents exposed to metallic mercury. METHOD: participants were 52 adolescents, of both genders, who presented hearing thresholds within normal limits. The study group (SG) was composed by 21 adolescents who worked on the burning of gold-mercury amalgams, on the re-burning of gold in stores that sell this metal or who lived next to gold mines or gold shops. The control group (CG) was composed by 31 adolescents who had no history of exposure to mercury. Investigation procedures included the application of a clinical, occupational and mercury exposure history questionnaire, basic audiometric assessment as well as central auditory processing tests. RESULTS: Statistical significant differences in the auditory processing tests of non-verbal sound sequence memory test (p = 0,001), frequency pattern test (p = 0,000), duration pattern test (p = 0,000) and SSW test in Portuguese (p = 0,006) were observed between SG and CG. CONCLUSION:adolescents exposed to metallic mercury presented a lower performance on most of the auditory processing tests when compared to those who had no history of exposure to mercury. The main deficit found in the study was related to difficulty in distinguishing successive brief sounds.

Bacterial sensing of and resistance to gold salts.

The MerR family is a group of bacterial transcriptional regulators that respond to different environmental stimuli, such as heavy metals, oxidative stress or antibiotics. Here we characterize a new member of this family that is highly selective for Au ions. We show that this Salmonella regulator, named GolS, directly controls the expression of at least two transcriptional units specifically required for Au resistance. By chromosomal mutagenesis, we demonstrated that Au-selectivity is accomplished by a metal-binding motif in GolS. Among the monovalent metal-ion sensing MerR regulators GolS clusters in a branch distant from enterobacterial CueR orthologues. We propose that GolS and its homologues evolved to cope with toxic concentration of Au ion, allowing microorganisms to withstand contaminated environments.

Morphological alterations of central nervous system (CNS) myelin in vanadium (V)-exposed adult rats.

In the present work we show morphological data of the in vivo susceptibility of CNS myelin to sodium metavanadate [V(+5)] in adult rats. The possible role of vanadium in behavioral alterations and in brain lipid peroxidation was also investigated. Animals were injected intraperitoneally (i.p.) with 3 mg/kg body weight (bw) of sodium metavanadate [1.25 V/kg bw/day] for 5 consecutive days. Open field and rotarod tests were performed the day after the last dose had been administered and then animals were sacrificed by different methods for histological and lipid peroxidation studies. The present results show that intraperitoneal administration of V(+5) to adult rats resulted in changes in locomotor activity, specific myelin stainings and lipid peroxidation in some brain areas. They support the notion that CNS myelin could be a preferential target of V(+5)-mediated lipid peroxidation in adult rats. The mechanisms underlying this action could affect the myelin sheath leading to behavioral perturbations.