Effects of dams on As and Hg concentrations in three southeastern Brazil fluvial systems: Ocean inputs, sources and seasonal dynamics among environmental compartments.

Damming rivers for hydropower generation interferes in the flow of water bodies and, consequently, in trace element biogeochemistry and transport. This study focused on the effects of dams on the seasonal dynamics of arsenic (As) and mercury (Hg) in three fluvial systems (Itabapoana River, Flechas Channel and Paraíba do Sul River) and on the input of these elements to the ocean. The elements were evaluated in suspended particulate matter (SPM), surface sediments, and the roots of the aquatic macrophyte Eichhornia crassipes. Our results showed that the proximity of the dams in the Flechas Channel and Rio Itabapoana in relation to their mouth (distances of 4 km and 58 km, respectively) changed As and Hg seasonal dynamics in the environmental compartments analyzed, with the Flechas Channel being the most impacted area. In contrast, the lower part of the Paraíba do Sul River that has more distant dams to its mouth (distance of 184 km) did not show such marked changes, suggesting that most of the inputs are coming from the long river reach. The isotopic and elemental composition of organic matter indicated the soils of native forests as the main source of trace elements to the water bodies. Flow rate was the main driver controlling As and Hg ocean inputs, with higher inputs observed in the Paraíba do Sul River (9.69 and 0.59 t∙year-1, respectively) compared to the other assessed fluvial systems. Also, this study demonstrated that, if a dam is closer to the mouth of a river, less contaminants will be input.

Influence of Iron on Physiological Parameters and Intracellular Microcystin in Microcystis Panniformis Strain Isolated from a Reservoir in the Amazon.

In the Amazon, the leaching from soil left unprotected by deforestation increases the entry of iron, among other elements, in aquatic ecosystems, which can cause cyanobacterial blooms. This study aimed to investigate the physiological response of a strain of Microcystis panniformis to iron variation. The strain was isolated from a reservoir located in the Western Amazon and produces microcystin-LR. After a period of iron deprivation, the cultures were submitted to three conditions: control (223 µgFe.L-1), treatment with 23 µgFe.L-1, and absence of iron. At regular intervals for eight days, the cell density, levels of chlorophyll a and microcystins were determined. On the second and fourth day, transcription of genes responsive to iron limitation was quantified. Starting on the fourth day of the experiment, the different iron concentrations affected growth, and on the eighth day in the iron-free condition cell density was 90% lower than in control. Chlorophyll cell quota in 23 µgFe.L-1 and control presented similar values, while without iron the cells became chlorotic as of the fourth day Toxin concentration in cells grow in 0 µgFe.L-1 in relation to the control. Higher transcription levels of the feo and fut genes were observed in the 0 µgFe.L-1 and 23 µgFe.L-1 treatments, indicating that the cells were activating high-affinity capture systems to reestablish an adequate concentration of intracellular iron. The increasing deforestation in the Jamari River Basin (Amazon region), can contribute to the occurrence of toxic cyanobacterial blooms due to the greater entrance of iron in water bodies.

Arsenic in the lower drainage basin of the Paraíba do Sul River (Southeast Brazil): dynamics between the water column and sediment.

The presence of arsenic (As) in the sediment and the particulate and dissolved fractions of the water column determines its behavior and bioavailability. The main geochemical parameters responsible for As mobility are organic matter and oxide-forming metals such as Fe. The As distribution and its concentration were evaluated in the dissolved fraction, suspended particulate matter (SPM) and sediment of the lower Paraíba do Sul River (PSR), its main tributaries (Muriaé, Pomba, and Dois Rios rivers), and flooded and estuarine areas. As was not detected in the dissolved fraction. The river flow influenced the As concentration in the SPM, which was higher in the dry season than in the rainy season (2.6 ± 0.69 and 1.98 ± 0.29 mg kg-1, respectively). The Fe oxyhydroxides, organic carbon, and surface area measured in the sediment were positively related with As concentration (R2 = 0.11, 0.34, and 0.30; p < 0.05). The highest As concentrations in the sediment occurred in the secondary estuary and flooded areas (5.16 ± 4.78 and 1.23 ± 0.44 mg kg-1, respectively), in which finer granulometric fractions (silt and clay) predominated (64% and 71%, respectively), in addition to greater surface area. The measurement of stable carbon and nitrogen isotopes (δ13C and δ15N) and atomic ratio (C:N)a indicated the existence of a combination of autochthonous and allochthonous sources of organic matter composing the SPM. In general, the As concentrations in the sediment and SPM were low, with values below that permitted by Brazilian regulations (5.9 mg kg-1), which suggests that the As sources in the lower basin of the PSR are diffuse and natural.

Exposure to toxic and essential trace elements through the intake of processed and meat cuts (beef and chicken) in southeastern Brazil.

The present study evaluated the concentration of six trace elements in processed meat products and in meat cuts. We also assessed the risk associated with the consumption of these foods based on the estimated daily intake (EDI) of these elements. Fifty-eight processed meat and 148 meat cuts samples were analyzed using ICP-OES. As and Cd were not detected in any sample of processed meat. The highest mean level of lead was observed in frankfurters (0.056 µg g-1), which is half the maximum permissible level. For Cr, the highest mean concentrations were detected in chicken nuggets and beef hamburger (0.121 and 0.105 µg g-1, respectively), which are above the allowed limit. The comparison between the impact of a diet restricted to processed meats with a diet restricted to meats cuts showed that the individuals following the latter are exposed to higher amounts of the trace elements analyzed.

The impact of hydroelectric dams on mercury dynamics in South America: A review.

The increase in global demand for electric energy is reflected in plans to construct numerous hydroelectric dams in South America that can cause chronic ecological impacts if not built and managed correctly. One of the main impacts generated by hydropower dams is the accumulation of Hg chemical species in their reservoir compartments and the downstream transport of these contaminants. Hg circulation in these environments has been studied for 27 years and this review brings a synthesis of the dynamics that are now well established, so that future studies can focus on gaps and inconsistent results in the literature. The topics cover the methylation process of Hg, its transfer along the trophic chain and the impacts downstream from dams. In addition, meta-analyses are used to propose regression models that explain Hg dispersion in environmental compartments of reservoirs, using as predictors morphological, spatial and temporal aspects of these environments.

Arsenic Exposure and Effects in Humans: A Mini-Review in Brazil.

Arsenic (As) is widely studied in several countries due to its toxicity to biota in the environment. Arsenic sources may be natural or anthropogenic, and the mobility of the element is ruled by physicochemical conditions that also define the dominant As species in the environment. Arsenic levels are evaluated in various abiotic and biotic environmental samples. The highest As levels are observed in sediment, from where it may be mobilized into the aquifers. This article reviews studies about As in the world but with emphasis on studies performed in Brazil, a country where continental water bodies are a common geographic feature. We reviewed 64 studies published between 1985 and 2016. The results indicate that in recent years more studies have been conducted to determine As levels in foods and human samples as a tool to evaluate the exposure of populations and identify potential sources. In Brazil, the main problems associated with contamination with As are the use of wood preservatives and herbicides as well as the impact caused by mining. Also, the precarious character of sewage treatment systems contributes to the contamination of water bodies.

Risk of exposure to total and inorganic arsenic by meat intake among different age groups from Brazil: a probabilistic assessment.

Beef and poultry as well as cattle and chicken livers are staple food items for Brazilian population, and previous studies had detected arsenic levels in these foods. This study aims to evaluate the risk of exposure to total and inorganic arsenic by meat intake in three age groups from Brazil (11-16, 16-21, and > 21 years). Our hypotheses are (i) that there is differences in the risk of exposure between age groups and (ii) the older individuals (> 21 years) are under higher risk. To test these hypotheses, we calculated the probabilistic estimated daily intake of total As (TAsEDI) from poultry, beef, cattle liver, and chicken liver, and the probabilistic estimated incremental lifetime skin, bladder, and lung cancer risk (ILCR) associated with inorganic As ingestion from poultry only. TAsEDI and ILCR from poultry differed among groups which confirm the first hypothesis. However, TAsEDI and ILCR results cannot support the second hypothesis. Even though the age groups are under a low risk of exposure to As by meat intake, the results indicate that bladder/lung cancer risk (from poultry intake) slightly exceeds the safe limits in the older population.

Impact of Land Use on the Mobility of Hg Species in Different Compartments of a Tropical Watershed in Brazil.

This study evaluated the levels of total Hg and CH3Hg+ from a comprehensive perspective, considering the retention, leaching, and deposition of these contaminants in the main compartments (soil, plant litter, and sediment) of three landscapes (Atlantic Forest, pasture, and agricultural area) in a watershed in northern Rio de Janeiro State, Brazil. Variables analyzed were total Hg, CH3Hg+, organic carbon, total nitrogen, grain size, and surface area. In soil samples, total Hg levels were the highest in agricultural soil followed by forest soil and pasture (97.3, 87.6, and 77.1 ng g-1, respectively), and CH3Hg+ was lower than 1.7%. Total Hg levels in leaf litter varied between 22.6 and 34.2 ng g-1, and CH3Hg+ was 4.37%. In sediment, Hg (60-180 ng g-1) and CH3Hg+ (<1%) indicate the transport of these contaminants from soils to this compartment and may be associated with soil use and cover. Multiple regressions were used to understand the dispersion of Hg species, and the effect of each variable varied with the landscape, showing that plant cover should not be ignored in investigations related to Hg species retention in a watershed. The landscapes surveyed in the present study clearly influence the quantitative and qualitative distribution of Hg species. On the other hand, anthropic processes associated with changes in soil use did not have any critical effects on the absolute levels of total Hg and CH3Hg+, meaning that the landscapes evaluated seem to represent the background concentration of these chemical species for the evaluated watershed.

Intestinal toxicity evaluation of long-circulating and pH-sensitive liposomes loaded with cisplatin.

Cisplatin (CDDP) is a chemotherapeutic agent widely used in several anticancer protocols for instance head and neck, testicle, ovarian, lung and peritoneal carcinomatosis. According to the literature, the use of CDDP is associated with several side effects; among them, we highlighted the mucositis. CDDP, when administered by IP, promoted significant intestinal epithelium alterations in an experimental model. Our research group has proposed that the incorporation of CDDP into long-circulating and pH-sensitive liposomes (SpHL-CDDP) could help to overcome some side effects induced by this drug. Thus, we evaluated signs of intestinal toxicity 24h and 72h after the administration of a single i.p dose of free CDDP or SpHL-CDDP to healthy Swiss mice. Twenty-four hours after administration of free CDDP, the mice showed signs of intestinal toxicity, principally weight loss, increased intestinal permeability associated with a decrease in expression of tight junctions, and histological damage with the presence of inflammatory infiltrates and activation of ERK1/2 and NF-κB. These changes persisted after 72h. While signs of intestinal toxicity were also observed 24h after administration of SpHL-CDDP, after 72h body weight and intestinal permeability of mice in this group were similar to those of mice in the control group. In comparison with the free CDDP treatment group, 72h after treatment mice in the SpHL-CDDP group showed better histological parameters, lower levels of inflammatory infiltrate with increased IL-10 and IgA levels, and less activation of caspase-3, ERK1/2 and NF-κB. These differences could account for the recovery of the intestinal epithelium observed in mice treated with SpHL-CDDP but not in mice treated with free CDDP. In conclusion, here we show that encapsulation of CDDP in SpHL lessens intestinal damage and that, as such, SpHL-CDDP is a promising candidate for clinical use.

Pretreatment and Treatment With L-Arginine Attenuate Weight Loss and Bacterial Translocation in Dextran Sulfate Sodium Colitis.

BACKGROUND: Imbalances in a variety of factors, including genetics, intestinal flora, and mucosal immunity, can contribute to the development of ulcerative colitis and its side effects. This study evaluated the effects of pretreatment or treatment with arginine by oral administration on intestinal permeability, bacterial translocation (BT), and mucosal intestinal damage due to colitis. METHODS: C57BL/6 mice were distributed into 4 groups: standard diet and water (C: control group), standard diet and dextran sodium sulfate (DSS) solution (Col: colitis group), 2% L-arginine supplementation for 7 days prior to DSS administration and during disease induction (PT: pretreated group), and 2% L-arginine supplementation during disease induction (T: treated group). Colitis was induced by administration of 1.5% DSS for 7 days. After 14 days, intestinal permeability and BT were evaluated; colons were collected for histologic analysis and determination of cytokines; feces were collected for measurement of immunoglobulin A (IgA). RESULTS: The Col group showed increased intestinal permeability (C vs Col: P < .05) and BT (C vs Col: P < .05). In the arginine-supplemented groups (PT and T), this amino acid tended to decrease intestinal permeability. Arginine decreased BT to liver during PT (P < .05) and to blood, liver, spleen, and lung during T (P < .05). Histologic analysis showed that arginine preserved the intestinal mucosa and tended to decreased inflammation. CONCLUSIONS: Arginine attenuates weight loss and BT in mice with colitis.

Synthesis of nitroaromatic compounds as potential anticancer agents.

Twenty-seven nitrated and non-nitrated compounds have been synthesized and tested for their growth inhibitory activity on three human cancer cells lines. Fourteen compounds were able to inhibit more than 50% of the growth of at least one of the cancer cell lines and five compounds exhibited high antiproliferative activity on human cancer cell lines (IC50 < 8.5 µM). The cytotoxicity of the compounds on Vero cell line was established in vitro to evaluate the selectivity. All active compounds have a good leaving group (bromide or chloride) at the benzylic position, indicating that the mechanism of action of these compounds is related to their alkylating properties. Two compounds (3 and 24) were selected for further studies in mice with Ehrlich solid tumors and display significant antitumor effects in vivo.

Combination therapy with carboplatin and thalidomide suppresses tumor growth and metastasis in 4T1 murine breast cancer model.

Carboplatin, efficient cytostatics for cancer therapy, could induce apoptosis and inhibit the growth of vascular endothelium in several tumor cell lines and xenograft models. It has been suggested that the antitumor effect of chemotherapy could be increased by combining it with an antiangiogenesis agent in anticancer strategy. The present study explored the potential to increase the antitumor effect of carboplatin by combining it with thalidomide in mouse 4T1 breast cancer models, and the underlining mechanism was investigated. The systemic administration of carboplatin and thalidomide significantly decreased tumor growth through increased tumor cell apoptosis compared with either control group. Collectively, these findings suggest that combined treatment has shown synergistic suppression in tumor progression according to the analysis. Furthermore, also was observed reduction in number of lung metastases as compared to isolated treatments and increased survival of the animals. The present study may be important in future exploration of the potential application of the combined approach in the treatment of breast cancer.

Long-circulating, pH-sensitive liposomes versus long-circulating, non-pH-sensitive liposomes as a delivery system for tumor identification.

Bombesin (BBN) is a tetradecapeptide that binds specifically to gastrin-releasing peptide receptors in humans. Several forms of cancer, including lung, prostate, breast, and colon over-express receptors for bombesin-like peptides. Therefore, radiolabeled bombesin analogs might be useful for tumor identification. Nevertheless, it is well known that higher tumor uptake can yield images in higher quality. Hence, drug delivery systems, such as liposomes, can be used to achieve a higher concentration of radiotracer in tumor site, and also improve the radiotracer stability, since peptides can suffer easily degradation in vivo by natural plasma and tissue peptides. In this paper, we prepared long-circulating, pH-sensitive liposomes and long-circulation, non-pH sensitive liposomes. Both formulations were able to encapsulate the radiolabeled bombesin derivative (99mTc-BBN(7_14)), and also showing high in vitro stability. Biodistribution studies were performed in Ehrlich tumor bearing-mice to compare the ability of pH-sensitive and non-pH sensitive liposomes to deliver 99mTc-BBN(7_14) to tumor site. Results showed higher tumor uptake (2-fold) when pH-sensitive liposomes were used, suggesting that these vesicles can facilitate the access to the tumor by releasing the diagnostic agent into the ideal area. As a result, tumor-to-muscle ratio achieved with pH-sensitive liposomes was higher than that obtained with non-pH-sensitive formulation. In addition, scintigraphic images for pH-sensitive liposomes showed evident tumor uptake, corroborating with biodistribution data. Therefore, the results presented in this paper suggest that pH-sensitive liposomes are able to deliver more efficiently the radiolabeled bombesin analog. This finding poses a new possibility to improve images quality, since the tumor-to-muscle ratio was strongly enhanced.

Antitumor effectiveness and toxicity of cisplatin-loaded long-circulating and pH-sensitive liposomes against Ehrlich ascitic tumor.

Cisplatin (CDDP) is one of the most active cytotoxic agents commonly used in the treatment of peritoneal carcinomatosis. The disadvantages of its clinical use are systemic side-effects, such as nephrotoxicity and myelotoxicity. Long-circulating and pH-sensitive liposomes containing CDDP (SpHL-CDDP) were developed by our research group aiming to promote the release of CDDP near the tumor as well as decreasing toxicity. The aim of this study was to evaluate the antitumor efficacy and toxicity of SpHL-CDDP after intraperitoneal administration in initial or disseminated tumor-bearing mice, at a dose of 12 mg/kg. The survival was monitored and blood samples were collected for biochemical and hematological analysis. Kidneys, liver and spleen were removed for histopathological examination. Tumor cells were evaluated for cellular viability and cell cycle. The survival of animals treated with SpHL-CDDP was higher than those treated with free CDDP. The cell death caused by treatment with SpHL-CDDP occurred through induction of apoptosis, with a cell cycle arrest at the G0/G1 phase. The treatment of mice presenting initial cancer with both formulations provoked a suppression of granulocytes. Mice treated with free CDDP also showed a decrease in platelet count, which suggests a high myelotoxicity. In an advanced cancer model, SpHL-CDDP treatment allowed an improvement of the immune response. Mice affected by cancer at an early stage and treated with free CDDP or SpHL-CDDP showed a lower urea/creatinine index compared with the saline control group. These findings indicate that both treatments were able to reduce the renal damage caused by peritoneal carcinomatosis. Microscopic analysis of kidneys from mice treated with SpHL-CDDP showed a discrete morphological alteration, while tubular necrosis was observed for free CDDP-treated mice. Concerning hepatotoxicity, no alteration in clinical chemistry parameters was observed. These findings reveal that SpHL-CDDP can improve the antitumor efficacy and decrease renal and bone marrow toxicity.

Antitumoral activity and toxicity of PEG-coated and PEG-folate-coated pH-sensitive liposomes containing ¹59Gd-DTPA-BMA in Ehrlich tumor bearing mice.

In the present study, PEG-coated pH-sensitive and PEG-folate-coated pH-sensitive liposomes containing the ¹59Gd-DTPA-BMA were prepared and radiolabeled through neutron activation technique, aiming to study the in vivo antitumoral activity and toxicity on mice bearing a previously-developed solid Ehrlich tumor. The treatment efficacy was verified through tumoral volume increase and histomorphometry studies. The toxicity of formulations was investigated through animal weight variations, as well as hematological and biochemical tests. The results showed that after 31 days of treatment, animals treated with radioactive formulations had a lower increase in tumor volume and a significantly higher percentage of necrosis compared with controls revealed by histomorphometry studies. Furthermore, mice treated with radioactive formulations exhibited lower weight gain without significant hematological or biochemical changes, except for toxicity to hepatocytes which requires more detailed studies. From the results obtained to date, we believe that the radioactive formulations can be considered potential therapeutic agents for cancer.