RESUMO
The field study aims to address identified research gaps by providing valuable information on the concentration, spatial distribution, pollution levels, and source apportionment of toxic and essential elements in sediment samples from four sampling sites (P1: Beira Rio (urban area), P2: Bananal (rural area), P3: Embiral (rural area), P4: Cidelândia (rural area) distributed along the middle Tocantins River, Brazil. Samples were collected in 2023 from river sections and analyzed using various contamination índices (geoaccumulation index, contamination factor, enrichment factor, pollution load index, sediment pollution index, potential ecological risk coefficients, and integrated risk index). Results indicated that the levels of aluminum, iron, manganese, and selenium exceeded legal standards in that year. Chromium, nickel, copper, zinc, and lead exceeded guidelines, mainly in section P1 for aluminum and section P3 for nickel and lead. Rainy months showed increased presence, indicating seasonal variability. The geoaccumulation index indicated low pollution levels, with lead and nickel notably present near urban and industrial areas. The enrichment factor highlighted elevated concentrations of lead and zinc in industrial areas. Both PLI and SPI indices raise concerns regarding Pb (P4) and Zn (P3) concentrations at specific times of the year. Overall, potential ecological risks were deemed low for most sites. Continuous monitoring and interventions are crucial to preserve water and environmental quality in the region.
Assuntos
Monitoramento Ambiental , Sedimentos Geológicos , Rios , Poluentes Químicos da Água , Brasil , Sedimentos Geológicos/análise , Sedimentos Geológicos/química , Rios/química , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Pradaria , Humanos , Medição de Risco , Metais Pesados/análiseRESUMO
Anhydroecgonine Methyl Ester (AEME), also known as methylecgonidine, is the main pyrolysis product of smoking cocaine (cocaine base paste or basuco, crack, or freebase). This review aims to synthesize the available scientific evidence on the toxicokinetic and toxicodynamic effects of AEME. A search of scientific articles published in Science Direct, SCOPUS, and MEDLINE up to May 2024 was conducted. Twenty-four articles, including 13 experimental animal studies, 2 clinical trials, and 3 observational studies, were reviewed. AEME is readily deposited in the alveoli; its absorption improves in combination with cocaine and has a broad tissue distribution. It is metabolized primarily in the liver, with a half-life of approximately one hour, and is mainly excreted through urine. Moreover, AEME acts as a partial agonist of M1 and M3 muscarinic cholinergic receptors, influences dopaminergic system neuroadaptation, increases the production of reactive oxygen species, imbalances the activity of glutathione-associated enzymes, and reduces melatonin levels, affecting its antioxidant regulatory properties. When combined with cocaine, AEME activates the non-apoptotic pathway of caspase-9 and then, the apoptotic pathway via caspase-8, reducing neuronal viability in half the time of cocaine. AEME plays a significant role in cocaine toxicity and AEME itself.
RESUMO
The search for bioactive compounds in natural products holds promise for discovering new pharmacologically active molecules. This study explores the anti-inflammatory potential of açaí (Euterpe oleracea Mart.) constituents against the NLRP3 inflammasome using high-throughput molecular modeling techniques. Utilizing methods such as molecular docking, molecular dynamics simulation, binding free energy calculations (MM/GBSA), and in silico toxicology, we compared açaí compounds with known NLRP3 inhibitors, MCC950 and NP3-146 (RM5). The docking studies revealed significant interactions between açaí constituents and the NLRP3 protein, while molecular dynamics simulations indicated structural stabilization. MM/GBSA calculations demonstrated favorable binding energies for catechin, apigenin, and epicatechin, although slightly lower than those of MCC950 and RM5. Importantly, in silico toxicology predicted lower toxicity for açaí compounds compared to synthetic inhibitors. These findings suggest that açaí-derived compounds are promising candidates for developing new anti-inflammatory therapies targeting the NLRP3 inflammasome, combining efficacy with a superior safety profile. Future research should include in vitro and in vivo validation to confirm the therapeutic potential and safety of these natural products. This study underscores the value of computational approaches in accelerating natural product-based drug discovery and highlights the pharmacological promise of Amazonian biodiversity.
Assuntos
Anti-Inflamatórios , Inflamassomos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Inflamassomos/antagonistas & inibidores , Inflamassomos/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Euterpe/química , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
Resumen Los hongos con amatoxinas son los que generan la mayor cantidad de intoxicaciones mortales por mice tismo en el planeta. Estas toxinas son producidas no solo por las especies de Amanita, como la muy conocida Amanita phalloides, sino también por otros géneros, entre los que se encuentra Lepiota. En este trabajo se expone el tratamiento de un paciente de 51 años con un peso de 79 kg, derivado al hospital luego de 36 h de haber ingerido hongos, los cuales fueron identificados como Lepiota brunneoincarnata, en nuestro conocimiento una especie hallada por primera vez en la Argentina. El paciente presentaba malestar general, con náuseas y repetidos vómitos acompañados de dolor abdominal y diarrea. Gracias a una rápida anamnesis e identificación aproximada y temprana del hongo se le colocó sonda nasogástrica y se suministró carbón activado seriado. Además de N-acetilcisteína, fitomenadiona y penicilina G EV. El paciente fue dado de alta a los 11 días de su ingreso. Este caso realza la importancia de obtener una anamnesis correcta y suficiente sobre hongos, poder rea lizar un rápido análisis de ellos e iniciar un tratamiento oportuno de la intoxicación. Queda demostrado, una vez más, la importancia de tener Centros de Información y Asesoramiento Toxicológico (CIAT) con experiencia y conocimiento de micetismos.
Abstract Mushrooms containing amatoxins generate the high est number of fatal mycete poisonings on the planet. These toxins are produced not only by Amanita species, such as the well-known Amanita phalloides, but also by other genera, including Lepiota. In this work we report the treatment of a 51-year-old male patient weighing 79 kg who was referred to the hospital after 36 h of ingesting mushrooms. The mushrooms were identified as Lepiota brunneoincarnata, found for the first time in Argentina. The patient presented general malaise, nausea and repeated vomiting, abdominal pain, and diarrhea. Thanks to a quick anamnesis and early and accurate identifica tion of the fungus, he was administered a nasogastric tube and serial activated charcoal. Additionally, N-ace tylcysteine, phytomenadione and penicillin G EV were administered. The patient was discharged 11 days after admission. This case highlights the importance of obtain ing a correct and sufficient anamnesis on fungi, enabling rapid analysis of them, and initiation of timely treatment for intoxication. Once again, the importance of having Toxicological Information and Advice Centers (CIAT) with experience and knowledge of micetisms is demonstrated.
RESUMO
Cyanobacterial harmful algal blooms can pose risks to ecosystems and human health worldwide due to their capacity to produce natural toxins. The potential dangers associated with numerous metabolites produced by cyanobacteria remain unknown. Only select classes of cyanopeptides have been extensively studied with the aim of yielding substantial evidence regarding their toxicity, resulting in their inclusion in risk management and water quality regulations. Information about exposure concentrations, co-occurrence, and toxic impacts of several cyanopeptides remains largely unexplored. We used liquid chromatography-mass spectrometry (LC-MS)-based metabolomic methods associated with chemometric tools (NP Analyst and Data Fusion-based Discovery), as well as an acute toxicity essay, in an innovative approach to evaluate the association of spectral signatures and biological activity from natural cyanobacterial biomass collected in a eutrophic reservoir in southeastern Brazil. Four classes of cyanopeptides were revealed through metabolomics: microcystins, microginins, aeruginosins, and cyanopeptolins. The bioinformatics tools showed high bioactivity correlation scores for compounds of the cyanopeptolin class (0.54), in addition to microcystins (0.54-0.58). These results emphasize the pressing need for a comprehensive evaluation of the (eco)toxicological risks associated with different cyanopeptides, considering their potential for exposure. Our study also demonstrated that the combined use of LC-MS/MS-based metabolomics and chemometric techniques for ecotoxicological research can offer a time-efficient strategy for mapping compounds with potential toxicological risk. Environ Toxicol Chem 2024;43:2222-2231. © 2024 SETAC.
Assuntos
Biomassa , Cianobactérias , Metabolômica , Cianobactérias/metabolismo , Brasil , Microcistinas/toxicidade , Microcistinas/metabolismo , Microcistinas/análise , Cromatografia Líquida , Animais , Monitoramento Ambiental/métodosRESUMO
In recent years, emerging environmental pollutants have increasingly endangered the health of freshwater organisms. The gut microbiota exhibits sensitivity to medications, dietary factors and environmental pollutants, rendering it a novel target for toxicological studies. The gut microbiota can be a potential exposure route affecting the host's health. Herein, we review the current knowledge on two different but concurrent pollutants, microplastics and pesticides, regarding their impact on the gut microbiota, which includes alterations in microbial composition, gene expression, function, and health effects in the hosts. Moreover, synergetic interactions between microplastics and pesticides can exacerbate dysbiosis and health risks. We discuss health-related implications of gut microbial changes based on the consequences in metabolism, immunity, and physiology function. Further research is needed to discover the mechanisms underlying these effects and develop strategies for mitigating their harmful impacts on freshwater animals.
Assuntos
Água Doce , Microbioma Gastrointestinal , Microplásticos , Praguicidas , Poluentes Químicos da Água , Microbioma Gastrointestinal/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Microplásticos/toxicidade , Animais , Praguicidas/toxicidadeRESUMO
The aim of this study was to evaluate the sensitivity of the prawn Palaemon argentinus to the pyrethroid cypermethrin (CYP) and the tetramic acid spirotetramat (STM). These treatments were compared with prawns collected at a reference site to define their basal physiological state. Initially, physicochemical parameters and several pollutants at the selected site were analyzed. The LC50-96 h was determined in adult prawns. Then, prawns were exposed for 96 h to sublethal concentrations of CYP (0.0005 µg/l) and STM (0.44 mg/l) to evaluate the effects on some biochemical endpoints. A treatment combining both pesticides was also added at 5 % of these values. Controls with and without solvent (acetone) were included. The LC50-96 h values were 0.005 µg/l and 4.43 mg/l for CYP and STM, respectively. Moreover, some biomarkers linked to oxidative and energy metabolism were analyzed in the hepatopancreas and muscle of both essayed prawns and those at the basal state. The STM caused a significant decrease in total protein content (32 %) in contrast to the increase of protein carbonyl content (71 %) (p < 0.05). Also, glutathione S-transferase (52 %) and catalase (61 %) activities in the hepatopancreas of exposed prawns were higher compared to both the control and state basal groups (p < 0.05). In muscle, only a significant decrease in the lactate content (69 %) was caused by STM (p < 0.05). In addition, CYP caused a significant increase in the lactate dehydrogenase activity (110 %) in muscle and triacylglycerol content (73 %) in the hepatopancreas (p < 0.05). The integrated biomarker index (IBRv2) analysis showed that STM caused greater damage than CYP. Besides, the combined treatment showed an antagonistic interaction between both insecticides. The differential response of biomarkers to both CYP and STM exposure with respect to their basal levels shows a high sensitivity of P. argentinus demonstrating its potential role as a bioindicator organism.
Assuntos
Biomarcadores , Inseticidas , Palaemonidae , Piretrinas , Compostos de Espiro , Poluentes Químicos da Água , Animais , Palaemonidae/efeitos dos fármacos , Inseticidas/toxicidade , Piretrinas/toxicidade , Compostos de Espiro/toxicidade , Poluentes Químicos da Água/toxicidade , Biomarcadores/metabolismo , Compostos Aza/toxicidade , Hepatopâncreas/efeitos dos fármacos , Hepatopâncreas/metabolismoRESUMO
Atomoxetine is a drug widely used for the treatment of the attention deficit hyperactivity disorder (ADHD) with reduced risk of adverse motor reactions and chemical dependence. However, the pharmacokinetics characteristics as well as the toxicological risk of atomoxetine deserves further investigation to comprehensively analyze the therapeutic and safety aspects of this drug. This study aimed to predict the physicochemical profile and medicinal chemistry characteristics of atomoxetine, alongside its pharmacokinetic properties-namely absorption, distribution, metabolism, and excretion-as well as its toxicology (ADMET) potential through the utilization of web-based in silico tools. This research emphasizes predicted physicochemical, medicinal chemistry, and absorption parameters of atomoxetine that could influence the efficacy and safety of this drug for ADHD treatment. Additionally, atomoxetine also presents noteworthy predicted risks of hepatotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity, respiratory system toxicity, skin toxicity, and carcinogenicity. These findings underscore the necessity for further assessments of atomoxetine's safety profile, particularly considering different patient populations and durations of drug treatment. The data reported here from in silico predictions suggest that closer monitoring is warranted when atomoxetine is administered to patients with ADHD. Moreover, controlled studies detailing reliable protocols for personalized dosing, considering the multifactorial variability in metabolism efficiency and toxicological potential, would enable a more comprehensive assessment of atomoxetine's safety profile.
RESUMO
Lorcaserin is a 5-hydroxytryptamine 2C (serotonin) receptor agonist and a nongenotoxic rat carcinogen, which induced mammary tumors in male and female rats in a 2-yr bioassay. Female Sprague Dawley rats were treated by gavage daily with 0, 30, or 100 mg/kg lorcaserin, replicating bioassay dosing but for shorter duration, 12 or 24 wk. To characterize exposure and eliminate possible confounding by a potentially genotoxic degradation product, lorcaserin and N-nitroso-lorcaserin were quantified in dosing solutions, terminal plasma, mammary, and liver samples using ultra-high-performance liquid chromatography-electrospray tandem mass spectrometry. N-nitroso-lorcaserin was not detected, supporting lorcaserin classification as nongenotoxic carcinogen. Mammary DNA samples (n = 6/dose/timepoint) were used to synthesize PCR products from gene segments encompassing hotspot cancer driver mutations, namely regions of Apc, Braf, Egfr, Hras, Kras, Nfe2l2, Pik3ca, Setbp1, Stk11, and Tp53. Mutant fractions (MFs) in the amplicons were quantified by CarcSeq, an error-corrected next-generation sequencing approach. Considering all recovered mutants, no significant differences between lorcaserin dose groups were observed. However, significant dose-responsive increases in Pik3ca H1047R mutation were observed at both timepoints (ANOVA, P < 0.05), with greater numbers of mutants and mutants with greater MFs observed at 24 wk as compared with 12 wk. These observations suggest lorcaserin promotes outgrowth of spontaneously occurring Pik3ca H1047R mutant clones leading to mammary carcinogenesis. Importantly, this work reports approaches to analyze clonal expansion and demonstrates CarcSeq detection of the carcinogenic impact (selective Pik3ca H0147R mutant expansion) of a nongenotoxic carcinogen using a treatment duration as short as 3 months.
Assuntos
Classe I de Fosfatidilinositol 3-Quinases , Mutação , Ratos Sprague-Dawley , Animais , Feminino , Classe I de Fosfatidilinositol 3-Quinases/genética , Glândulas Mamárias Animais/efeitos dos fármacos , Glândulas Mamárias Animais/metabolismo , Ratos , Carcinógenos/toxicidade , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/genética , Relação Dose-Resposta a Droga , BenzazepinasRESUMO
Mushrooms containing amatoxins generate the highest number of fatal mycete poisonings on the planet. These toxins are produced not only by Amanita species, such as the well-known Amanita phalloides, but also by other genera, including Lepiota. In this work we report the treatment of a 51-year-old male patient weighing 79 kg who was referred to the hospital after 36 h of ingesting mushrooms. The mushrooms were identified as Lepiota brunneoincarnata, found for the first time in Argentina. The patient presented general malaise, nausea and repeated vomiting, abdominal pain, and diarrhea. Thanks to a quick anamnesis and early and accurate identification of the fungus, he was administered a nasogastric tube and serial activated charcoal. Additionally, N-acetylcysteine, phytomenadione and penicillin G EV were administered. The patient was discharged 11 days after admission. This case highlights the importance of obtaining a correct and sufficient anamnesis on fungi, enabling rapid analysis of them, and initiation of timely treatment for intoxication. Once again, the importance of having Toxicological Information and Advice Centers (CIAT) with experience and knowledge of micetisms is demonstrated.
Los hongos con amatoxinas son los que generan la mayor cantidad de intoxicaciones mortales por micetismo en el planeta. Estas toxinas son producidas no solo por las especies de Amanita, como la muy conocida Amanita phalloides, sino también por otros géneros, entre los que se encuentra Lepiota. En este trabajo se expone el tratamiento de un paciente de 51 años con un peso de 79 kg, derivado al hospital luego de 36 h de haber ingerido hongos, los cuales fueron identificados como Lepiota brunneoincarnata, en nuestro conocimiento una especie hallada por primera vez en la Argentina. El paciente presentaba malestar general, con náuseas y repetidos vómitos acompañados de dolor abdominal y diarrea. Gracias a una rápida anamnesis e identificación aproximada y temprana del hongo se le colocó sonda nasogástrica y se suministró carbón activado seriado. Además de N-acetilcisteína, fitomenadiona y penicilina G EV. El paciente fue dado de alta a los 11 días de su ingreso. Este caso realza la importancia de obtener una anamnesis correcta y suficiente sobre hongos, poder realizar un rápido análisis de ellos e iniciar un tratamiento oportuno de la intoxicación. Queda demostrado, una vez más, la importancia de tener Centros de Información y Asesoramiento Toxicológico (CIAT) con experiencia y conocimiento de micetismos.
Assuntos
Intoxicação Alimentar por Cogumelos , Masculino , Pessoa de Meia-Idade , Humanos , Intoxicação Alimentar por Cogumelos/terapia , Argentina , Resultado do TratamentoRESUMO
Cadmium (Cd) is a heavy metal that acts as endocrine disrupting chemical (EDC). Few studies have investigated the effects of Cd exposure on metabolic dysfunctions, such as type 1 and 2 diabetes mellitus (T1DM and T2DM). Thus, we assessed whether subacute Cd exposure at occupational levels causes abnormalities in white adipose tissue (WAT), liver, pancreas, and skeletal muscle. We administered cadmium chloride (CdCl2) (100 ppm in drinking water for 30 days) to female rats and evaluated Cd levels in serum and metabolic organs, morphophysiology, inflammation, oxidative stress, fibrosis, and gene expression. High Cd levels were found in serum, WAT, liver, pancreas, and skeletal muscle. Cd-exposed rats showed low adiposity, dyslipidemia, insulin resistance, systemic inflammation, and oxidative stress compared to controls. Cd exposure reduced adipocyte size, hyperleptinemia, increased cholesterol levels, inflammation, apoptosis and fibrosis in WAT. Cd-exposed rats had increased liver cholesterol levels, insulin receptor beta (IRß) and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1α) expression, karyomegaly, inflammation, and fibrosis. Cd exposure reduced insulin levels and pancreatic islet size and increased inflammation and fibrosis. Cd exposure reduced skeletal muscle fiber diameter and increased IR expression and inflammation. Finally, strong positive correlations were observed between serum, tissue Cd levels, abnormal morphology, tissue inflammation and fibrosis. Thus, these data suggest that subacute Cd exposure impairs WAT, liver, pancreas and skeletal muscle function, leading to T1DM and T2DM features and other complications in female rats.
Assuntos
Cádmio , Diabetes Mellitus Tipo 2 , Fígado , Animais , Feminino , Diabetes Mellitus Tipo 2/induzido quimicamente , Ratos , Cádmio/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Estresse Oxidativo/efeitos dos fármacos , Diabetes Mellitus Tipo 1/induzido quimicamente , Ratos Wistar , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Disruptores Endócrinos/toxicidadeRESUMO
This study investigated lead (Pb) and cadmium (Cd) transfer in three dairy farming areas in the Mantaro river headwaters in the central Peruvian Andes and at varying distances from the mining complex at La Oroya. At each of these sites, the transfer of trace metals from the soil to raw milk was estimated, and a hazard assessment for lead and cadmium was carried out in scenarios of minimum, average, and maximum milk consumption in a Peruvian population aged 2-85. Pb and Cd were quantified by flame atomic absorption spectrometry. Significantly, the concentrations of lead and cadmium were found to exceed the maximum limits recommended by the World Health Organization, with a positive geospatial trend correlated with the distance from mining activity. Both Pb and Cd were found to be transferred through the soil-pasture-milk pathway, with the primary source of Cd being phosphate-based fertilizers used in pasture improvement. Pb was found to be the most significant contributor to the Hazard Index (HI) with those under 19 years of age and over 60 recording an HI of >1, with infants being the most vulnerable group due to their greater milk consumption in relation to their body weight. A marginal increase in contamination was observed in the dry season, indicating the need for studies to be expanded over several annual cycles.
RESUMO
The most recent dam rupture in Brazil released tons of mining tailings into the upper course of the Paraopeba River, affecting this river in an unprecedented way. The present study aimed to evaluate the influence of heavy metals on Prochilodus costatus, an important commercial species in Brazil, four years after the dam colapse. To this end, biomarkers of heavy metals, oxidative stress, and environmental stress were analyzed, and histological analyses of target organs were performed. The results demonstrated critical contamination of fish from the Paraopeba River. Increased expression of Metallothioneins - MTs, Heat Shock Protein - HSP70, and inducible nitric oxide synthase - iNOS, as well as greater rates of histological changes in the liver, spleen, and gonads, were observed in P. costatus. These findings demonstrate that, despite past contamination, the metals present in mining tailings have significantly increased the contamination of the Paraopeba River basin.
Assuntos
Fígado , Metalotioneína , Metais Pesados , Óxido Nítrico Sintase Tipo II , Rios , Poluentes Químicos da Água , Animais , Metalotioneína/metabolismo , Poluentes Químicos da Água/toxicidade , Metais Pesados/toxicidade , Óxido Nítrico Sintase Tipo II/metabolismo , Brasil , Fígado/efeitos dos fármacos , Fígado/metabolismo , Baço/efeitos dos fármacos , Baço/metabolismo , Caraciformes/metabolismo , Masculino , Gônadas/efeitos dos fármacos , Gônadas/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteínas de Peixes/metabolismo , FemininoRESUMO
Hydroxychloroquine (HCQ) is a safe antimalarial drug but its overdosage or inappropriate use, such as during the pandemic, may cause adverse effects once this drug is considered a potent inhibitor of autophagy. Information about HCQ's effects on the reproductive field, including gametes and initial embryos, is limited. In this study, we evaluated the effect of HCQ (1, 6, 12, and 24 µM) on pre-implantation embryo development, autophagy, and apoptosis of bovine embryos produced in vitro. A dose-response experiment showed a reduction (p < 0.05) in cleavage only at the highest concentration. Blastocyst rate was gradually reduced (p < 0.05) with the increase of HCQ dosage starting at 6 µM, with no embryo formation occurring at 24 µM. Further analysis showed that embryos treated with 12 µM of HCQ had a higher (p < 0.05) accumulation of acidic autophagic vesicles on Days 5 and 7 of development and a higher (p < 0.01) apoptotic index on Day 7. To our knowledge, this is the first study to evaluate the effects of HCQ on embryo pre-implantation development in mammals. The results contribute with more information related to the study of autophagy in embryology as well as add some discussion on HCQ toxicology and its effects on reproductive cells.
Assuntos
Apoptose , Autofagia , Blastocisto , Desenvolvimento Embrionário , Hidroxicloroquina , Animais , Bovinos , Hidroxicloroquina/toxicidade , Desenvolvimento Embrionário/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Blastocisto/efeitos dos fármacos , Feminino , Antimaláricos/toxicidade , Fertilização in vitro , Técnicas de Cultura EmbrionáriaRESUMO
The capacity of particulate matter (PM) to enhance and stimulate the expression of pro-inflammatory mediators has been previously demonstrated in non-antigen-presenting cells (human bronchial epithelia). Nonetheless, many proposed mechanisms for this are extrapolated from known canonical molecular pathways. This work evaluates a possible mechanism for inflammatory exacerbation after exposure to PM2.5 (from Puerto Rico) and CuSO4, using human bronchial epithelial cells (BEAS-2B) as a model. The induction of CIITA, MHCII genes, and various pro-inflammatory mediators was investigated. Among these, the phosphorylation of STAT1 Y701 was significantly induced after 4 h of PM2.5 exposure, concurrent with a slight increase in CIITA and HLA-DRα mRNA levels. INFγ mRNA levels remained low amidst exposure time, while IL-6 levels significantly increased at earlier times. IL-8 remained low, as expected from attenuation by IL-6 in the known INFγ-independent inflammation pathway. The effects of CuSO4 showed an increase in HLA-DRα expression after 8 h, an increase in STAT1 at 1 h, and RF1 at 8 h We hypothesize and show evidence that an inflammatory response due to PM2.5 extract exposure in human bronchial epithelia can be induced early via an alternate non-canonical pathway in the absence of INFγ.
RESUMO
The Reloncaví estuary in southern Chile is famous for its aquaculture. However, recurring harmful algal blooms have adversely affected mussel production. Therefore, regular monitoring of algal toxins is urgently needed to better understand the contamination status of the estuary. In this study, we quantified 15 types of lipophilic shellfish toxins in Metri Bay in the Reloncaví estuary on a biweekly basis for 4 years. We identified algal species using microscopy and metabarcoding analysis. We also measured water temperature, salinity, chlorophyll-a, and dissolved oxygen to determine the potential relationships of these parameters with algal toxin production. Our results revealed the presence of a trace amount of pectenotoxin and the causal phytoplankton Dinophysis, as well as yessotoxin and the causal phytoplankton Protoceratium. Statistical analysis indicated that fluctuations in water temperature affected the detection of these toxins. Additionally, metabarcoding analysis detected the highly toxic phytoplankton Alexandrium spp. in some samples. Although our results suggest that the level of lipophilic shellfish toxins in Metri Bay during the study period was insignificantly low using our current LC-MS method, the confirmed presence of highly toxic algae in Metri Bay raises concerns, given that favorable environmental conditions could cause blooms.
Assuntos
Monitoramento Ambiental , Estuários , Proliferação Nociva de Algas , Toxinas Marinhas , Fitoplâncton , Chile , Toxinas Marinhas/análise , Animais , DinoflagellidaRESUMO
Tourism is one of the most important activities for the economy of Nor Patagonia Argentina. In Bariloche City, located on the shores of Lake Nahuel Huapi, both the permanent and the temporary populations have increased significantly in recent decades, and this has not necessarily been accompanied by an improvement in sewage networks. Emerging micropollutants such as pharmaceutical compounds reach aquatic systems directly, in the absence of a domestic sewage network, or through effluents from wastewater treatment plants (WWTP), which do not efficiently remove these substances and represent a major threat to the environment. Therefore, the objective of our study was to monitor the presence of pharmaceutical compounds discharged both through wastewater effluents and diffusely from housing developments into Lake Nahuel Huapi. The results obtained demonstrate the presence of pharmaceuticals in Lake Nahuel Huapi with concentrations ranging from not detectable (ND) to 110.6 ng L-1 (caffeine). The highest pharmaceutical concentration recorded in WWTP influent corresponded to caffeine (41728 ng L-1), and the lowest concentration was paracetamol (18.8 ng L-1). The removal efficiency of pharmaceuticals in the WWTP was calculated, and ranged from 0% for carbamazepine to 66% for ciprofloxacin. This antibiotic showed the lowest % of attenuation (73%) in Lake Nahuel Huapi. These results on the occurrence of a wide variety of pharmaceuticals are the first generated in Patagonia, representing a regional baseline for this type of micropollutant and valuable information for the subsequent design of removal strategies for emerging pharmaceutical pollutants in surface water. Environ Toxicol Chem 2024;43:1274-1284. © 2024 SETAC.
Assuntos
Monitoramento Ambiental , Lagos , Poluentes Químicos da Água , Argentina , Poluentes Químicos da Água/análise , Lagos/química , Preparações Farmacêuticas/análise , Águas Residuárias/químicaRESUMO
The aim of this work was to evaluate the toxicological action of AH Plus (AHP), Bio-C Sealer (BCS), and EndoSequence BC Sealer (ESB), using Drosophila melanogaster as the model organism performing in vivo and ex vivo analysis. D. melanogaster were exposed for 10 days to three concentrations (5 mg/ml, 10 mg/ml, and 20 mg/ml) of AHP, BCS, and ESB sealers mixed with 10 ml of standard diet. During this period, the mortality of flies was evaluated. On the 11th day, the locomotor activity test was performed and the flies were euthanized for oxidative damage analysis (reactive species and lipid peroxidation) and cell viability (resazurin reduction). For the mortality curves evaluation, the log-rank test (Mantel-Cox) was used. For the analysis of other data, a one-way analysis of variance (ANOVA) was applied, followed by Tukey's post hoc test (α = 0.05). Regarding mortality, there were no significant differences. The locomotor activity was reduced, mainly in the two highest concentrations of AHP and BCS. Besides, reactive species generation was bigger in the AHP 20 mg/ml group. AHP induced a lipid peroxidation increase in all three concentrations tested, when compared to other sealers. Considering cell viability, the two highest concentrations of AHP reduced this parameter; while in other sealers, viability was reduced only in the highest concentration. AHP showed changes in oxidative markers that led to greater damage to the flies.
Assuntos
Sobrevivência Celular , Drosophila melanogaster , Peroxidação de Lipídeos , Estresse Oxidativo , Materiais Restauradores do Canal Radicular , Animais , Drosophila melanogaster/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Materiais Restauradores do Canal Radicular/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Resinas Epóxi/toxicidade , Teste de MateriaisRESUMO
Introduction: 5-fluorouracil (5-FU) and methotrexate (MTX) are the antineoplastic drugs most commonly used worldwide. Considered cytotoxic, these pharmaceuticals exhibit low specificity, causing damage not only to cancer cells but also to healthy cells in organisms. After being consumed and metabolized, these drugs are excreted through urine and feces, followed by wastewater treatment. However, conventional treatments do not have the capacity to completely remove these substances, risking their introduction into freshwater systems. This could pose a risk to human health even at low concentrations. Aims: Thus, the present study aimed to investigate the genotoxicity, cytotoxicity, and mutagenicity of 5-FU and MTX at environmentally relevant concentrations after a long-term exposure, using adult male rats as an experimental model. Methods: Male Wistar rats (70 days old) were distributed into 4 groups (n = 10/group): control, received only vehicle; MTX, received methotrexate at 10ngL-1; 5-FU received 5-fluorouracil at 10ngL-1; and MTX + 5-FU, received a combination of MTX and 5-FU at 10ngL-1 each. The period of exposure was from postnatal day (PND) 70 to PND 160, through drinking water. After that, the animals were euthanized and the samples (liver, testis, femoral bone marrow, and peripheral blood) were obtained. Results: Increased DNA fragmentation was observed in the peripheral blood, liver, and testis, altering the parameters of the tail moment and tail intensity in the Comet assay. Besides, the change in the ratio between PCE and NCE indicates bone marrow suppression. Conclusion: These findings warn the adverse effects for the general population worldwide chronically exposed to these drugs at trace concentration unintentionally.
RESUMO
INTRODUCTION: Self-medication is the use of drugs to treat self-diagnosed illnesses or symptoms, on one's own initiative, without the guidance of a healthcare professional. Poison centers play an important role in understanding the relationship between self-medication and poisoning. The objective of this study is to evaluate the clinical and epidemiological profile of patients exposed to and/or poisoned by different drugs through self-medication. METHODS: This retrospective, cross-sectional, and descriptive study analyzed data from 2014 to 2020, provided by the Toxicological Information and Assistance Center of Santa Catarina, Brazil. Data were selected, tabulated, and analyzed by using descriptive statistics and group comparison with the chi-square test or Fisher's exact test. A P value <0.05 was considered statistically significant. RESULTS: There were 683 cases of self-medication identified. Most patients were female (62.8 percent) and between 20 and 29 years old (26.1 percent). A toxic dose of a substance was administered in only 22.8 percent of the cases, and five deaths were recorded. The most commonly used medications were anxiolytics (18 percent), followed by analgesics and antipyretics (15.4 percent). Paracetamol was the drug used in three of the five cases that resulted in deaths. DISCUSSION: This study demonstrates the prevalence of self-medication among women aged between 20 and 29 years old. Statistical analysis failed to show a relationship between a toxic dose and clinical manifestations. Anxiolytics, analgesics, and antipyretics are the most reported medications probably because healthcare professionals are mostly the ones who contact the center. Analgesics and antipyretics account for more than fifty percent of the deaths caused by self-medication in the present report. Some limitations such as secondary sources are related. CONCLUSION: We highlight the importance of health professionals in promoting the rational use of medicines, as well as poison centers in assisting the population and raising their awareness regarding the issue.