ABSTRACT
Mercury behavior upon resuspension of sediments from two impacted areas of Guanabara Bay was evaluated to assess worst-case methylmercury (MeHg) responses, under dark experimental conditions to prevent demethylation by photolysis. Study areas include the Rio de Janeiro Harbor (RJH) and the chlor-alkali plant-affected Meriti River (MR) estuary. Total mercury (THg) and MeHg concentrations were determined along 24-h experiments of sediment resuspension in the bay water in dark conditions. Fine-grained Meriti River (MR) estuary sediments had 8 times higher MeHg initial concentrations than sandy Rio de Janeiro Harbor (RJH) sediments (3.4 ± 0.29 vs. 0.41 ± 0.1 ng g-1, respectively). Though THg contents were uncorrelated with resuspension time, statistically significant correlations of MeHg (rs = 0.78) and %MeHg in relation to THg (rs = 0.86) with resuspension time were observed for RJH sediments, indicating net methylation only for this study site. These positive correlation trends correspond to a 2.8 times MeHg concentration increase (ΔMeHg = 0.75 ng g-1) and 4.4 times increase in %MeHg (Δ%MeHg = 1.0%), after 24 h of resuspension. This suggests that assessments of factors affecting the MeHg spatial-temporal variability and associated toxicity risks can be limited in some sites if concentration changes due to sediment resuspension-redeposition processes are not considered. Therefore, the inclusion of MeHg evaluation before and after sediment resuspension events is recommendable for the improvement of dredging licensing and monitoring activities.
Subject(s)
Mercury , Methylmercury Compounds , Water Pollutants, Chemical , Alkalies , Brazil , Environmental Monitoring , Geologic Sediments , Mercury/analysis , Methylation , Water , Water Pollutants, Chemical/analysisABSTRACT
The xenotopic expression of the alternative oxidase AOX from the tunicate Ciona intestinalis in diverse models of human disease partially alleviates the phenotypic effects of mitochondrial respiratory chain defects. AOX is a non-proton pumping, mitochondrial inner membrane-bound, single-subunit enzyme that can bypass electron transport through the cytochrome segment, providing an additional site for ubiquinone reoxidation and oxygen reduction upon respiratory chain overload. We set out to investigate whether AOX expression in Drosophila could counteract the effects of mitochondrial DNA (mtDNA) replication defects caused by disturbances in the mtDNA helicase or DNA polymerase γ. We observed that the developmental arrest imposed by either the expression of mutant forms of these enzymes or their knockdown was not rescued by AOX. Considering also the inability of AOX to ameliorate the phenotype of tko25t, a fly mutant with mitochondrial translation deficiency, we infer that this alternative enzyme may not be applicable to cases of mitochondrial gene expression defects. Finding the limitations of AOX applicability will help establish the parameters for the future putative use of this enzyme in gene therapies for human mitochondrial diseases.
Subject(s)
DNA Replication , DNA, Mitochondrial/genetics , Drosophila Proteins/metabolism , Drosophila melanogaster/growth & development , Mitochondria/pathology , Mitochondrial Diseases/physiopathology , Mitochondrial Proteins/metabolism , Oxidoreductases/metabolism , Plant Proteins/metabolism , Animals , Drosophila Proteins/genetics , Drosophila melanogaster/enzymology , Drosophila melanogaster/genetics , Electron Transport , Female , Genes, Lethal , Male , Mitochondria/genetics , Mitochondria/metabolism , Mitochondrial Proteins/genetics , Mutation , Oxidoreductases/genetics , Phenotype , Plant Proteins/geneticsABSTRACT
We describe herein the discovery of (E)-N-methyl-N'-((5-nitrofuran-2-yl)methylene)benzo[d]( 1 , 3 ) dioxole-5-carbohydrazide (9e), named LASSBio-1215, as a novel antiplatelet agent belonging to the N-methyl-N-acylhydrazone class, which exert their antiaggregating actions on human and rabbit platelets induced by different agonists, through cyclooxygenase-1 (COX-1) or thromboxane synthase inhibition. This compound was elected after screening of a series of functionalized furyl N-acylhydrazone derivatives, synthesized from natural safrole 10. In vitro assays showed that compound 9e presents platelet-aggregating activity in rabbit platelet-rich plasma (PRP) induced by arachidonic acid (IC(50) = 0.7 µM) and collagen (IC(50) = 4.5 µM). Moreover, LASSBio-1215 also inhibited almost completely the second wave of adenosine diphosphate-induced platelet aggregation in human PRP, and this effect was correlated with their ability to block the production of pro-aggregating autacoid thromboxane A(2).
Subject(s)
Benzodioxoles/pharmacology , Biological Products/pharmacology , Hydrazines/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Safrole/chemistry , Animals , Benzodioxoles/chemical synthesis , Benzodioxoles/chemistry , Biological Products/chemical synthesis , Biological Products/chemistry , Blood Platelets/drug effects , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Humans , Hydrazines/chemical synthesis , Hydrazines/chemistry , Molecular Structure , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/chemical synthesis , Platelet Aggregation Inhibitors/chemistry , Rabbits , Reference ValuesABSTRACT
PURPOSE: Metal bioavailability-based sediment quality analysis, inferred from geochemical partitioning data, may contribute to improve sediment management policies. This is important because decision-making processes should not give similar priorities to sediments offering contrasting environmental risks associated to metal bioavailability. However, current uses of Sediment Quality Guidelines (SQGs) as interpretive tools to support decisions about dredging-related activities have not considered the changes in metal bioavailability upon sediment resuspension. METHODS: Sediments from a Cu-contaminated site in Guanabara Bay (Brazil) were submitted to 16-h resuspension experiments in estuarine water to assess the susceptibility of Cu mobilization to the dissolved phase and alteration in the solid phase partitioning between a potentially bioavailable (1 mol/l HCl-extractable) phase and concentrated HNO(3)-extractable phase. RESULTS: After sediment resuspensions, dissolved Cu levels became slightly lower (in a surface water-resuspension treatment) or slightly higher (in a bottom water-resuspension treatment). In both treatments, the 1 mol/l HCl-extractable solid phase concentrations changed from seven times lower to two times higher values than an SQG adopted in Brazilian legislation. This change was explained by a transition from concentrated HNO(3)-extractable phases to reactive HCl-extractable phases upon resuspension. CONCLUSIONS: An evaluation of metal susceptibility to present geochemical partitioning changes, as can be inferred from HCl-extractable fraction analyses before and after resuspension experiments, is recommended as an additional criterion to assess environmental risks of sediment dredging in relation to resuspension-sensitive metals, such as Cu.
Subject(s)
Conservation of Natural Resources , Copper/pharmacokinetics , Geologic Sediments/analysis , Water Pollutants, Chemical/analysis , Water Pollution, Chemical/prevention & control , Biological Availability , Brazil , Guidelines as Topic , Risk AssessmentABSTRACT
This study investigates the effects on fish and assesses human health hazards from mercury released in two gold mining areas in Indonesia: Tatelu (North Sulawesi Province) and Galangan (Katingan District, Central Kalimatan Province). In Tatelu, 154 fish specimens of 10 freshwater species were collected, as well as five marine species from the fish market. The mean concentration of total mercury in muscles of freshwater fish from this area was 0.58+/-0.44 microg/g, with more than 45% of fish having Hg levels above the WHO guideline for human consumption of 0.5 microg/g. In Galangan, where 263 fish specimens of 25 species were collected, the total mercury in muscles averaged 0.25+/-0.69 microg/g. Excluding data from flooded open pits in sub-area P4, mean Hg levels in fish from Galangan were 2 to 4 times lower than 0.5 microg/g, while fewer than 10% of fish from Galangan exceeded WHO guidelines. The Hazard Quotient (HQ) was applied to both areas to determine the threat of MeHg exposure for communities in both areas. The HQ is a risk assessment indicator which defines the ratio of exposure level to a single substance in relation to a reference dose. Samples from Tatelu (excluding marine species) had an HQ above one, while those from Galangan resulted in values of 2.4 for the whole area and 9.9 for sub-area P4, pointing to potentially harmful fish consumption for the local population. By using the single-compartment model to estimate mercury levels in blood and hair from daily intake dose, sub-area P4 showed the highest levels, higher than the upper limit guideline for pregnant women, but still lower than threshold levels associated with observed clinical effects.