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Glyphosate, a widely used herbicide, is linked to a plethora of deleterious effects in both clinical and preclinical studies. Nevertheless, the effects of its main metabolite, aminomethylphosphonic acid (AMPA), whose half-life in soil is even longer than that of glyphosate, have been little explored. On this basis, as a first approach, in this work, we report that intraperitoneal (i.p.) administration of AMPA or glyphosate (at 10, 56, and 100 mg/kg) decreased, to a similar extent, plasma cholinesterase (ChE) activity in acutely exposed rats. Moreover, we designed an experimental protocol to analyze and compare the effects of AMPA and glyphosate on human plasma ChE activity; this protocol consisted of adding these compounds to human plasma to subsequently test the effects of this plasma on the contraction to acetylcholine (ACh) in the frog rectus abdominis muscle (an indirect estimate of ChE activity). Accordingly, this muscular contraction to ACh was evaluated before and after pre-incubation of ACh with (i) plasma alone, (ii) plasma with AMPA, and (iii) plasma with glyphosate. Our results indicate that AMPA, like glyphosate, decreased ChE activity in the plasma of rats (when given i.p.) and humans (when added in vitro), suggesting that both xenobiotics may exert similar toxicological effects.
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Background: Chloramine-T (CL-T) is a synthetic sodium salt used as a disinfectant in fish farms to combat bacterial infections in fish gills and skin. While its efficacy in pathogen control is well-established, its reactivity with various functional groups has raised concerns. However, limited research exists on the toxicity of disinfection by-products to aquatic organisms. Therefore, this study aims to assess the sublethal effects of CL-T on adult zebrafish by examining biomarkers of nucleus cytotoxicity and genotoxicity, acetylcholinesterase (AChE) inhibition, and histopathological changes. Methods: Male and female adult zebrafish (wildtype AB lineage) specimens were exposed to 70, 140, and 200 mg/L of CL-T and evaluated after 96 h. Cytotoxic and genotoxic effects were evaluated by estimating the frequencies of nuclear abnormalities (NA), micronuclei (MN), and integrated optical density (IOD) of nuclear erythrocytes. Histopathological changes in the gills and liver were assessed using the degree of tissue changes (DTC). AChE activity was measured in brain samples. Results and conclusions: At a concentration of 200 mg/L, NA increased, indicating the cytogenotoxic potential of CL-T in adult zebrafish. Morphological alterations in the nuclei were observed at both 70 and 200 mg/L concentrations. Distinct IOD profiles were identified across the three concentrations. There were no changes in AChE activity in adult zebrafish. The DTC scores were high in all concentrations, and histological alterations suggested low to moderate toxicity of CL-T for adult zebrafish.
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Perciformes , Peixe-Zebra , Animais , Masculino , Feminino , Acetilcolinesterase , Cloraminas/toxicidade , Compostos de TosilRESUMO
BDE-47, a flame retardant that is frequently detected in environmental compartments and human tissues, has been associated with various toxic effects. In turn, information about the effects of aluminum diethyl-phosphinate (ALPI), a halogen-free flame retardant from a newer generation, is limited. This study aims to assess and compare the toxicity of BDE-47 and ALPI to zebrafish by analyzing the tail coiling, locomotor, acetylcholinesterase activities, and oxidative stress biomarkers. At 3000 µg/L BDE-47, the coiling frequency increased at 26-27 h post-fertilization (hpf), but the burst activity (%) and mean burst duration (s) did not change significantly. Here, we considered that the increased coiling frequency is a slight neurotoxic effect because locomotor activity was impaired at 144 hpf and 300 µg/L BDE-47. Moreover, we hypothesized that oxidative stress could be involved in the BDE-47 toxicity mechanisms. In contrast, only at 30,000 µg/L did ALPI increase the catalase activity, while the motor behavior during different developmental stages remained unaffected. On the basis of these findings, BDE-47 is more toxic than ALPI.
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This study investigated the effects of inosine on memory acquisition and consolidation, cholinesterases activities, redox status and Na+, K+-ATPase activity in a rat model of scopolamine-induced cognitive impairment. Adult male rats were divided into four groups: control (saline), scopolamine (1 mg/kg), scopolamine plus inosine (50 mg/kg), and scopolamine plus inosine (100 mg/kg). Inosine was pre-administered for 7 days, intraperitoneally. On day 8, scopolamine was administered pre (memory acquisition protocol) or post training (memory consolidation protocol) on inhibitory avoidance tasks. The animals were subjected to the step-down inhibitory avoidance task 24 hours after the training. Scopolamine induced impairment in the acquisition and consolidation phases; however, inosine was able to prevent only the impairment in memory consolidation. Also, scopolamine increased the activity of acetylcholinesterase and reduced the activity of Na+, K+-ATPase and the treatment with inosine protected against these alterations in consolidation protocol. In the animals treated with scopolamine, inosine improved the redox status by reducing the levels of reactive oxygen species and thiobarbituric acid reactive substances and restoring the activity of the antioxidant enzymes, superoxide dismutase and catalase. Our findings suggest that inosine may offer protection against scopolamine-induced memory consolidation impairment by modulating brain redox status, cholinergic signaling and ion pump activity. This compound may provide an interesting approach in pharmacotherapy and as a prophylactic against neurodegenerative mechanisms involved in Alzheimer's disease.
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Disfunção Cognitiva , Consolidação da Memória , Acetilcolinesterase/metabolismo , Animais , Colinérgicos/efeitos adversos , Inosina/efeitos adversos , Bombas de Íon/farmacologia , Bombas de Íon/uso terapêutico , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/prevenção & controle , Oxirredução , Estresse Oxidativo , Ratos , Ratos Wistar , Escopolamina/farmacologiaRESUMO
Psychiatric drugs are among the leading medications prescribed for humans, with their presence in aquatic environments raising concerns relating to potentially harmful effects on non-target organisms. Nortriptyline (NTP) is a selective serotonin-norepinephrine reuptake inhibitor antidepressant, widely used in clinics and found in environmental water matrices. In this study, we evaluated the toxic effects of NTP on zebrafish (Danio rerio) embryos and early larval stages. Developmental and mortality analyses were performed on zebrafish exposed to NTP for 168 h at concentrations ranging from 500 to 46,900 µg/L. Locomotor behaviour and acetylcholinesterase (AChE) activity were evaluated by exposing embryos/larvae to lower NTP concentrations (0.006-500 µg/L). The median lethal NTP concentration after 168 h exposure was 2190 µg/L. Although we did not identify significant developmental changes in the treated groups, lack of equilibrium was already visible in surviving larvae exposed to ≥ 500 µg/L NTP. The behavioural analyses showed that NTP was capable of modifying zebrafish larvae swimming behaviour, even at extremely low (0.006 and 0.088 µg/L) environmentally relevant concentrations. We consistently observed a significant reduction in AChE activity in the animals exposed to 500 µg/L NTP. Our results highlight acute toxic effects of NTP on the early-life stages of zebrafish. Most importantly, exposure to environmentally relevant NTP concentrations may affect zebrafish larvae locomotor behaviour, which in turn could reduce the fitness of the species. More studies involving chronic exposure and sensitive endpoints are warranted to better understand the effect of NTP in a more realistic exposure scenario.
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Inibidores da Captação Adrenérgica/toxicidade , Antidepressivos Tricíclicos/toxicidade , Nortriptilina/toxicidade , Inibidores Seletivos de Recaptação de Serotonina/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra , Acetilcolinesterase/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Larva/efeitos dos fármacos , Locomoção/efeitos dos fármacosRESUMO
Jaboticaba, Plinia cauliflora (Mart.) Kausel, is a Brazilian berry traditionally used in folk medicine as treatment for some health conditions. Phenolic compounds such as flavonoids and anthocyanins have previously been detected in the fruit. This current study aimed to evaluate the toxicological effects of jaboticaba peel extract (JPE) on Artemia salina, L929, and MDA-MB-231 cell lines. Besides, JPE antioxidant, acetylcholinesterase, and antifungal activities, and elemental analysis CHNS were also tested. JPE had moderate toxicity (LD50 = 360.92 µg mL-1) on A. salina, non-toxic effect on L929 cell line, and decreased the viability of cancer cell line MDA at 1,000 µg mL-1 and 500 µg mL-1 concentrations. The antioxidant activity toward 2,2-diphenyl-1-picrylhydrazyl (DPPH) performed IC50 = 37.45 ± 0.17 µg mL-1, whereas 45.7% of acetylcholinesterase activity was inhibited. By its elemental composition, JPE is an alternative food supplement and dermocosmetic component. Antifungal potential toward Candida strains was not observed.
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Bioensaio , Elementos Químicos , Myrtaceae/química , Compostos Orgânicos/análise , Testes de Toxicidade , Animais , Antifúngicos/farmacologia , Antioxidantes/farmacologia , Brasil , Candida/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologiaRESUMO
O Brasil é o maior consumidor global de agrotóxico tendo como consequência intoxicações de um grande número de trabalhadores, com altos gastos com a saúde e prejuízos ambientais. Objetivo geral: avaliar os efeitos do uso de agrotóxicos sobre a saúde de trabalhadores atuantes na agricultura familiar. Método: estudo transversal, analítico e comparativo entre o Grupo (1) composto por 80 trabalhadores rurais atuantes na agricultura familiar, expostos diretamente a agrotóxicos e o Grupo (2) composto por 60 usuários dos Programas de Saúde da Família (PSF) dos municípios de Capitólio e Pimenta - Minas Gerais - não diretamente expostos a agrotóxicos sendo o grupo controle por meio da análise de biomarcadores colinesterase eritrocitária e plasmática. Resultados: dos 140 participantes deste estudo, a maioria (51,2%) não referiu problemas de saúde e tratamento medicamentoso, 6,3% deles, expostos a agrotóxicos, referiram intoxicações e 42,5% relataram terem algum sinal e/ou sintoma de intoxicação com predominância (33,8%) para a dor de cabeça. O biomarcador colinesterase eritrocitária apresentou normalidade em 63,8% dos trabalhadores rurais e 36,2% com alteração na butirilcolinesterase. Conclusão: a butirilcolinesterase encontrada em 1/3 dos participantes expostos a agrotóxicos correlacionam-se à presença dos sintomas dor de cabeça e irritabilidade/nervosismo. Existe, portanto, a necessidade da educação e capacitação dos agricultores no uso de agrotóxicos para limitar níveis de exposição e efeitos nocivos à saúde para prevenir, diagnosticar e tratar possíveis disfunções causadas por esses produtos químicos
Brazil is the largest global consumer of pesticides, resulting in the intoxication of a large number of workers, with high expenditures on health and environmental damage. General objective: to evaluate the effects of the use of pesticides on the health of rural workers working in family farming in terms of intoxication through the evaluation of the erythrocyte and plasma cholinesterase biomarkers. Method: cross-sectional, analytical and comparative study between Group (1) of rural workers working in family farming, directly exposed to pesticides and Group (2) of users of Family Health Programs (PSF), in the municipalities of Capitólio and Pimenta - Minas Gerais State (Brazil) - not directly exposed to pesticides, being a control group through the analysis of biomarkers. Results: in this study of 140 participants, the most of them did not report health problems and drug treatment, 6.3% of participants, exposed to pesticides, reported poisoning and 42.5% reported having any signs and/or symptoms of intoxication with predominance for headache. The erythrocyte cholinesterase biomarker showed normality in 63.8% rural workers and 36.2% with alteration in butyrylcholinesterase. Conclusion: butyrylcholinesterase alteration was proven in 36.2% of participants exposed to pesticides and these results correlate with the presence of headache and irritability/nervousness symptoms. There is, therefore, a need for education and training of farmers to limit levels of exposure and harmful health effects to prevent, diagnose and treat possible dysfunctions caused by these chemicals applied to agriculture
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Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Riscos Ocupacionais , Biomarcadores , Saúde da População Rural , Exposição Ocupacional , Exposição a Praguicidas , AgriculturaRESUMO
portuguêsO Brasil é o maior consumidor global de agrotóxico tendo como consequência intoxicações de um grande número de trabalhadores, com altos gastos com a saúde e prejuízos ambientais. Objetivo geral: avaliar os efeitos do uso de agrotóxicos sobre a saúde de trabalhadores atuantes na agricultura familiar. Método: estudo transversal, analítico e comparativo entre o Grupo (1) composto por 80 trabalhadores rurais atuantes na agricultura familiar, expostos diretamente a agrotóxicos e o Grupo (2) composto por 60 usuários dos Programas de Saúde da Família (PSF) dos municípios de Capitólio e Pimenta - Minas Gerais - não diretamente expostos a agrotóxicos sendo o grupo controle por meio da análise de biomarcadores colinesterase eritrocitária e plasmática. Resultados: dos 140 participantes deste estudo, a maioria (51,2%) não referiu problemas de saúde e tratamento medicamentoso, 6,3% deles, expostos a agrotóxicos, referiram intoxicações e 42,5% relataram terem algum sinal e/ou sintoma de intoxicação com predominância (33,8%) para a dor de cabeça. O biomarcador colinesterase eritrocitária apresentou normalidade em 63,8% dos trabalhadores rurais e 36,2% com alteração na butirilcolinesterase. Conclusão: a butirilcolinesterase encontrada em 1/3 dos participantes expostos a agrotóxicos correlacionam-se à presença dos sintomas dor de cabeça e irritabilidade/nervosismo. Existe, portanto, a necessidade da educação e capacitação dos agricultores no uso de agrotóxicos para limitar níveis de exposição e efeitos nocivos à saúde para prevenir, diagnosticar e tratar possíveis disfunções causadas por esses produtos químicos
Brazil is the largest global consumer of pesticides, resulting in the intoxication of a large number of workers, with high expenditures on health and environmental damage. General objective: to evaluate the effects of the use of pesticides on the health of rural workers working in family farming in terms of intoxication through the evaluation of the erythrocyte and plasma cholinesterase biomarkers. Method: cross-sectional, analytical and comparative study between Group (1) of rural workers working in family farming, directly exposed to pesticides and Group (2) of users of Family Health Programs (PSF), in the municipalities of Capitólio and Pimenta - Minas Gerais State (Brazil) - not directly exposed to pesticides, being a control group through the analysis of biomarkers. Results: in this study of 140 participants, the most of them did not report health problems and drug treatment, 6.3% of participants, exposed to pesticides, reported poisoning and 42.5% reported having any signs and/or symptoms of intoxication with predominance for headache. The erythrocyte cholinesterase biomarker showed normality in 63.8% rural workers and 36.2% with alteration in butyrylcholinesterase. Conclusion: butyrylcholinesterase alteration was proven in 36.2% of participants exposed to pesticides and these results correlate with the presence of headache and irritability/nervousness symptoms. There is, therefore, a need for education and training of farmers to limit levels of exposure and harmful health effects to prevent, diagnose and treat possible dysfunctions caused by these chemicals applied to agriculture
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Humanos , Masculino , Feminino , Adulto , Riscos Ocupacionais , Biomarcadores , Colinesterases/toxicidade , Exposição Ocupacional/efeitos adversos , Exposição a Praguicidas , FazendeirosRESUMO
The anti-acetylcholinesterase, larvicidal, antifeedant activities and general toxicity of 15 semisynthetic eugenol derivatives based on clove oil (including the own oil), were evaluated against the maize armyworm, Spodoptera frugiperda (J.E. Smith). Therefore, promising eugenol molecules were classified with larvicidal, anti-acetylcholinesterase and antifeedant activities for controlling this pest. During structure-activity relationship studies and physicochemical profile analysis, it was found that among tested molecules 1-15, eugenol 1, prenyl eugenol 4, isoeugenol 8 and isoeugenol acetate 11 exhibited lethal effects LD50 at concentrations <1â¯mg/g of insect. On the other hand, eugenol 1, metallyl eugenol 3, isoeugenol 8 and isoeugenol acetate 11 showed a good antifeedant activity (CE50â¯=â¯158-209⯵g/mL) with a high antifeedant index (70-78%) at concentration 1000⯵g/mL, possessing a weak anti-acetylcholinesterase activity (IC50â¯=â¯21-31⯵g/mL). According to their ecotoxicological profiles (LC50â¯=â¯2033.1-6303.8⯵g/mL on Artemia salina larvae), isoeugenol 8 and its acetate derivative 11 could be potential used in control of the growth, feeding, or reproduction of S. frugiperda larvae, acting as moderate insecticidal acetylcholinesterase inhibitors and/or antifeedant molecules. Such structure-activity relationship studies could stimulate the identification of lead structures from natural sources for the development of larvicidal and deterrent products against S. frugiperda and related insect pests.
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The present study reports the biological evaluation of vanadium(V) complexes (1-3) against three different proteins: tyrosinase, acetylcholinesterase (AChE), and human serum albumin (HSA), which were studied by spectroscopic techniques and molecular docking. Despite the synthesis and characterization of complexes 1 and 2 having already previously described, complex 3 is a novel dioxidovanadium(V) derivative. Complex 1 can activate both tyrosinase and AChE enzymes in about 11.5 and 47.0%, respectively. On the other hand, complexes 2 and 3 inhibited the same enzymes (1.30 and 46.0% for tyrosinase and 20.0 and 21.9% for AChE, respectively). Molecular docking calculations suggested that the presence of the hydroxyl group in complex 1 is essential to activate tyrosinase enzymes. According to theoretical analysis, hydrogen bonding, van der Waals, and hydrophobic forces are the main binding interactions for each V(V) complex and AChE. Moreover, the interaction between HSA and vanadium(V) complexes occurs via ground-state association, being only enthalpically driven for complexes 1 and 2 and entropically and enthalpically driven for complex 3. The interaction is spontaneous for all samples and the binding modes do not perturb significantly the secondary and surface structures of the albumin. As there are few reported cases in the literature that explore vanadium complexes against these three proteins, the present results may contribute to future studies by offering different scaffolds to design new vanadium(V) complexes in the hyperpigmentation process and Alzheimer's disease.
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Acetilcolinesterase/química , Simulação de Acoplamento Molecular , Monofenol Mono-Oxigenase/química , Albumina Sérica Humana/química , Compostos de Vanádio/química , HumanosRESUMO
Dysfunction of basal ganglia neurons is a characteristic of glutaric acidemia type I (GA-I), an autosomal recessive inherited neurometabolic disease characterized by deficiency of glutaryl-CoA dehydrogenase (GCDH) and accumulation of glutaric acid (GA). The affected patients present clinical manifestations such as motor dysfunction and memory impairment followed by extensive striatal neurodegeneration. Knowing that there is relevant striatal dysfunction in GA-I, the purpose of the present study was to verify the performance of young rats chronically injected with GA in working and procedural memory test, and whether N-acetylcysteine (NAC) would protect against impairment induced by GA. Rat pups were injected with GA (5 µmol g body weight-1, subcutaneously; twice per day; from the 5th to the 28th day of life) and were supplemented with NAC (150 mg/kg/day; intragastric gavage; for the same period). We found that GA injection caused delay procedural learning; increase of cytokine concentration, oxidative markers, and caspase levels; decrease of antioxidant defenses; and alteration of acetylcholinesterase (AChE) activity. Interestingly, we found an increase in glial cell immunoreactivity and decrease in the immunoreactivity of nuclear factor-erythroid 2-related factor 2 (Nrf2), nicotinic acetylcholine receptor subunit alpha 7 (α7nAChR), and neuronal nuclei (NeuN) in the striatum. Indeed, NAC administration improved the cognitive performance, ROS production, neuroinflammation, and caspase activation induced by GA. NAC did not prevent neuronal death, however protected against alterations induced by GA on Iba-1 and GFAP immunoreactivities and AChE activity. Then, this study suggests possible therapeutic strategies that could help in GA-I treatment and the importance of the striatum in the learning tasks.
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Acetilcisteína/uso terapêutico , Neurônios Colinérgicos/efeitos dos fármacos , Glutaratos/toxicidade , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/prevenção & controle , Neuroglia/efeitos dos fármacos , Acetilcisteína/farmacologia , Animais , Neurônios Colinérgicos/metabolismo , Masculino , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Neuroglia/metabolismo , Ratos , Ratos WistarRESUMO
ABSTRACT Resistance profiles of houseflies (Gol-RR) collected from a field in Golmud city, Qinghai province, China, were determined for seven insecticides using topical bioassays. Resistance ratios of >1219.51, 153.17, >35.43, 6.12, 3.24, 1.73, and 0.86-fold were obtained for propoxur, cypermethrin, imidacloprid, indoxacarb, chlorpyrifos, fipronil, and chlorfenapyr, respectively, relative to a laboratory susceptible strain (SS). Synergism experiments showed that piperonyl butoxide (PBO), triphenylphosphate (TPP), and diethyl maleate (DEM) increased propoxur toxicity by >105.71, >7.88, and >5.15-fold in the Gol-RR strain, compared with 5.25, 2.00, and 1.39-fold in the SS strain, indicating the involvement of P450 monooxygenases, esterases, and glutathione-S-transferase in conferring resistance. Although cypermethrin resistance was significantly suppressed with PBO, TPP, and DEM in the Gol-RR strain, the synergistic potential of these agents to cypermethrin was similar in the SS strain, demonstrating that metabolism-mediated detoxification was not important for conferring resistance to cypermethrin in the Gol-RR strain. However, the three agents did not act synergistically with imidacloprid, indicating that other mechanisms may be responsible for the development of resistance to this insecticide. Acetylcholinesterase (AChE) activity was 13.70-fold higher in the Gol-RR than in the SS strain, suggesting the properties of the AChE enzyme were altered in the Gol-RR strain. Thus, rotation of chlorfenapyr insecticide with other agents acting through a different mode with minimal/no resistance could be an effective resistance management strategy for housefly.
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Resumen: Introducción: La detección temprana de sepsis es fundamental para disminuir la mortalidad de este padecimiento. Hasta el momento, ninguna escala clínica ni biomarcador ha sido útil en su diagnóstico y detección precoz. Los niveles de actividad de la acetilcolinesterasa se han propuesto como un biomarcador muy prometedor para la detección de sepsis y choque séptico. Objetivo: Estudiar la utilidad de los niveles de acetilcolinesterasa en el diagnóstico de sepsis. Material y métodos: Estudio observacional y prospectivo, en pacientes de la Unidad de Cuidados Intensivos del Hospital San Ángel Inn Universidad con diagnóstico de inestabilidad hemodinámica, clasificados con presencia o no de sepsis, tomándose niveles de acetilcolinesterasa al ingreso. Resultados: Se evaluaron 44 pacientes, 27% con sepsis. Los valores de acetilcolinesterasa tuvieron validez diagnóstica para predecir sepsis (AUC: 0.852 IC 95%: 0.726-0.977, p < 0.001), con un punto de corte de 3,956 U/L, sensibilidad = 81%, especificidad = 75%. El valor de neutrófilos con corte < 74% también tuvo valor predictor de sepsis (AUC: 0,710 IC 95%: 0,512-0,907, p = 0.034) sensibilidad = 75%, especificidad = 75%. Conclusiones: En pacientes con inestabilidad hemodinámica con niveles de acetilcolinesterasa mayores de 4,000 U/L se descarta sepsis como causa de choque.
Abstract: Introduction: Early detection of sepsis is essential to reduce mortality from this condition. So far, no clinical scale or biomarker has been useful in its diagnosis and early detection. Levels of acetylcholinesterase activity have been proposed as a very promising biomarker for the detection of sepsis and septic shock. Objective: To study the usefulness of acetylcholinesterase levels in the diagnosis of sepsis. Material and methods: Observational and prospective study in patients of the Intensive Care Unit of the Hospital San Ángel Inn Universidad with diagnosis of hemodynamic instability, classified with or without sepsis, taking acetylcholinesterase levels at admission. Results: 44 patients were evaluated, 27% with sepsis. The acetylcholinesterase values presented a normal distribution and had diagnostic validity to predict sepsis (AUC: 0.852 95% CI: 0.726-0.977, p < 0.001), with a cut-off value of < 3,956 U/L, sensitivity = 81%, specificity = 75%. The value of neutrophils with a cut < 74% also had a predictive value of sepsis (AUC: 0.710 95% CI: 0.512-0.907, p = 0.034) sensitivity = 75%, specificity = 75%. Conclusions: In patients with hemodynamic instability with acetylcholinesterase levels greater than 4,000 U/L, sepsis is ruled out as the cause of shock.
Resumo: Introdução: A detecção precoce da sepse é fundamental para reduzir a mortalidade desta doença. Até agora nenhuma escala clínica ou biomarcador tem sido útil em seu diagnóstico e detecção precoce. Os níveis de atividade da acetilcolinesterase têm sido propostos como um biomarcador muito promissor para a detecção de sepse e choque séptico. Objetivo: Estudar a utilidade dos níveis de acetilcolinesterase no diagnóstico da sepse. Material e métodos: Estudo observacional e prospectivo, realizado em pacientes da unidade de terapia intensiva do Hospital Universitário San Ángel Inn, com diagnóstico de instabilidade hemodinâmica, classificados com ou sem a presença de sepse, obtendo os níveis de acetilcolinesterase na admissão. Resultados: Foram avaliados 44 pacientes, 27% com sepse. Os valores de acetilcolinesterase apresentaram validade diagnóstica para predizer sepse (AUC: 0.852 IC 95%: 0.726-0.977, p < 0.001), com valor de corte 3956 U/L, sensibilidade = 81%, especificidade = 75%. O valor de neutrófilos com um corte < 74% também teve um valor preditivo de sepsis (AUC: 0.710 IC 95%: 0.512-0.907, p = 0.034) sensibilidade = 75%, especificidade = 75%. Conclusões: Em pacientes com instabilidade hemodinâmica com níveis de acetilcolinesterase superiores a 4,000 U/L a sepse é descartada como causa de choque.
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Little is known about biosecurity measures and toxic effects during pesticide application in the province of Jujuy, Argentina, particularly concerning the protective measures and mixture of pesticides used by rural workers. We carried out an observational study of agricultural workers from Jujuy (76 exposed subjects and 53 controls) to investigate the prevalence of chromosomal aberrations (CAs) in human lymphocytes as well as the activity level of acetylcholinesterase (AChE) in red blood cell erythrocytes. Whole blood samples (5 mL) were collected in heparinized Vacutainer tubes for cytogenetic analysis and erythrocyte cholinesterase activity determination according to Ellman's method. Cytogenetic results showed a significant CA increase in pesticide-exposed individuals as compared with controls (4.20 ± 0.15 vs. 1.00 ± 0.05, respectively; p < 0.001), suggesting that pesticides are clastogenic agents causing DNA damage. Erythrocyte cholinesterase activity was significantly lower in exposed individuals, evidencing the possible occurrence of perturbations in blood as well as neurotoxicity in pesticide sprayers. These results suggest the need for periodic biomonitoring of these biomarkers together with education and training of occupational workers for the safe application of potentially harmful pesticides.
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Doenças dos Trabalhadores Agrícolas/epidemiologia , Doenças dos Trabalhadores Agrícolas/genética , Aberrações Cromossômicas/estatística & dados numéricos , Fazendeiros , Mutagênicos/toxicidade , Exposição Ocupacional , Praguicidas/toxicidade , Acetilcolinesterase/sangue , Adulto , Idoso , Argentina/epidemiologia , Biomarcadores , Aberrações Cromossômicas/induzido quimicamente , Dano ao DNA , Monitoramento Ambiental , Eritrócitos/química , Eritrócitos/efeitos dos fármacos , Feminino , Humanos , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto JovemRESUMO
The pesticides cypermethrin (CYP) and chlorpyrifos (CPF) were found together in water bodies located in agricultural and urban areas. However, the impact to non-target biota from exposure to mixtures has received little attention. In the current study, we evaluated changes in swimming behavior and cholinesterase enzymes activity in Jenynsia multidentata, to investigate the possible effects of these insecticides individually and in mixtures. Moreover, differences between technical and commercial mixtures of the pesticides were evaluated. Females of J. multidentata were exposed over 96-h to CYP (0.04 and 0.4µgL(-1)), CPF (0.4 and 4µgL(-1)), individually and in a technical and commercial mixtures. Swimming behavior was recorded after 24h and 96h of exposure. Also, we measured cholinesterase enzymes activity in brain and muscle after 96h of exposure. Exposure to CYP increased the exploratory activity of J. multidentata in the upper area of the aquarium. Fish exposed to CPF (4µg L(-1)) showed a decrease in swimming activity and an increase in the time spent at the bottom of the aquarium. Interestingly, fish exposed to the technical and commercial mixture of CYP and CPF displayed a different behavior based on the concentration of exposure. Low concentration of pesticides elicited an increase in J. multidentata swimming activity with preference for the upper area of the aquarium, and high concentrations caused decrease in swimming activity with preference for the bottom area of the aquarium. Based on the response of cholinesterase enzymes, acetylcholinesterase in muscle was more sensitive to exposure to CYP, CPF and their mixtures than in brain. A decrease in swimming behavior correlates significantly with the inhibition of acetylcholinesterase activity in muscle of J. multidentata exposed to high concentrations of pesticides. These results draw attention to the need of more studies on the potential ecotoxicological impact of pesticides and its mixtures at environmental relevant concentrations.
Assuntos
Acetilcolinesterase/metabolismo , Clorpirifos/toxicidade , Ciprinodontiformes/fisiologia , Praguicidas/toxicidade , Piretrinas/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Feminino , Músculo Esquelético/efeitos dos fármacos , NataçãoRESUMO
Tissue accumulation of galactose is a hallmark in classical galactosemia. Cognitive deficit is a symptom of this disease which is poorly understood. The aim of this study was to investigate the effects of intracerebroventricular administration of galactose on memory (inhibitory avoidance and novel object recognition tasks) of adult rats. We also investigated the effects of galactose on acetylcholinesterase (AChE) activity, immunocontent and gene expression in hippocampus and cerebral cortex. Wistar rats received a single injection of galactose (4mM) or saline (control). For behavioral parameters, galactose was injected 1h or 24h previously to the testing. For biochemical assessment, animals were decapitated 1h, 3h or 24h after galactose or saline injection; hippocampus and cerebral cortex were dissected. Results showed that galactose impairs the memory formation process in aversive memory (inhibitory avoidance task) and recognition memory (novel object recognition task) in rats. The activity of AChE was increased, whereas the gene expression of this enzyme was decreased in hippocampus, but not in cerebral cortex. These findings suggest that these changes in AChE may, at least in part, to lead to memory impairment caused by galactose. Taken together, our results can help understand the etiopathology of classical galactosemia.
Assuntos
Acetilcolinesterase/metabolismo , Aprendizagem da Esquiva/efeitos dos fármacos , Galactose/toxicidade , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Acetilcolinesterase/genética , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/enzimologia , Comportamento Exploratório/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Inibição Psicológica , Injeções Intraventriculares , Masculino , Ratos , Ratos Wistar , Estatísticas não ParamétricasRESUMO
Background An endophytic fungus lives within a healthy plant during certain stages of, or throughout, its life cycle. Endophytic fungi do not always cause plant disease, and they include fungi that yield different effects, including mutual benefit, and neutral and pathogenic effects. Endophytic fungi promote plant growth, improve the host plant's resistance to biotic and abiotic stresses, and can produce the same or similar biologically active substances as the host. Thus, endophytic fungal products have important implications in drug development. Result Among the numerous endophytic fungi, we identified two strains, L10Q37 and LQ2F02, that have anti-acetylcholinesterase activity, but the active compound was not huperzine A. The aim of this study was to investigate the anti-acetylcholinesterase activity of secondary metabolites isolated from the endophytic fungi of Huperzia serrata. Microbial cultivation and fermentation were used to obtain secondary metabolites. Active components were then extracted from the secondary metabolites, and their activities were tracked. Two compounds that were isolated from endophytic fungi of H. serrata were identified and had acetylcholine inhibitory activities. In conclusion, endophytic fungal strains were found in H. serrata that had the same anti-acetylcholinesterase activity. Conclusion We isolated 4 compounds from the endophytic fungus L10Q37, among them S1 and S3 are new compounds. 6 compounds were isolated from LQ2F02, all 6 compounds are new compounds. After tested anti acetylcholinesterase activity, S5 has the best activity. Other compounds' anti acetylcholinesterase activity was not better compared with huperzine A.
Assuntos
Inibidores da Colinesterase , Huperzia , Endófitos , Desenvolvimento de MedicamentosRESUMO
Disulfated and trisulfated steroids have been synthesized from cholesterol and their acetylcholinesterase inhibitory activity has been evaluated. In our studies we have found that the activity was not only dependent on the location of the sulfate groups but on their configurations. 2ß,3α,6α-trihydroxy-5α-cholestan-6-one trisulfate (18) was the most active steroid with an IC50 value of 15.48 µM comparable to that of 2ß,3α-dihydroxy-5α-cholestan-6-one disulfate (1). Both compounds were found to be less active than the reference compound eserine. The butyrylcholinesterase activity of 1 and 18 was one magnitude lower than that against acetylcholinesterase revealing a selective inhibitor profile.
Assuntos
Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/farmacologia , Esteroides/síntese química , Esteroides/farmacologia , Sulfatos/química , Animais , Técnicas de Química Sintética , Inibidores da Colinesterase/química , Hidroxilação , Concentração Inibidora 50 , Esteroides/química , Relação Estrutura-Atividade , TorpedoRESUMO
An investigation was directed towards the antiacetylcholinesterase activity of the acid aqueous and methanolic extracts of five cyanobacterial taxa, which encompasses an enzymatic inhibition essay and the evaluation of the physiological responses of mice to cyanobacterial extracts along with toxicological observations. The strains Calothrix sp. CCIBt 3320, Tolypothrix sp. CCIBt 3321, Phormidium cf. amoenum CCIBt 3412, Phormidium sp. CCIBt 3265, and Geitlerinema splendidum CCIBt 3223 were from the São Paulo Botanical Institute Cyanobacterial Culture Collection and all of them showed inhibitory effect on acetylcholinesterase activity (in vitro) and caused systemic effects similar to those described for anticholinesterase drugs (in vivo). With the exception of G. splendidum and Tolypothrix sp. strains, all extracts produced reversible antiacetylcolinesterase effects in mice. Complementary histopathological studies were carried out on tissues from animals administered with Phormidium sp. and P. cf. amoenum.
RESUMO
Este trabalho descreve a composição química dos óleos essenciais e o isolamento de onze substâncias de Eupatorium ballotifolium Kunth, Asteraceae. Os óleos essenciais foram obtidos por hidrodestilação, analisados por CG-EM e avaliados quanto às suas atividades frente à enzima acetilcolinesterase. O rendimento dos óleos foi de 0,11 por cento para as folhas e 0,03 por cento para os talos. Os principais constituintes dos óleos foram os sesquiterpenos β-cariofileno (24,9 e 22,2 por cento), espatulenol (17,7 e 12,4 por cento) e epóxi-allo-aromadendreno (23,0 e 23,6 por cento). Do extrato hexânico da parte aérea foi isolada a mistura de β-sitosterol e estigmasterol, incluindo suas formas glicosiladas, e os triterpenos acetato de taraxasterila e taraxasterol, enquanto, do extrato etanólico foram isolados os flavonóides nepetina and 3-O-glicosil-quercetina. Do extrato hexânico das raízes foram isolados os triterpenos epi-friedelanol e damara-20,24-dien-3β-ol e do extrato etanólico a cumarina 11-hidroxi-11,12-di-hidroobliquina. As estruturas de todos os compostos foram determinadas usando técnicas espectroscópica tais como IV, EM e RMN ¹H e 13C.
This work describes the chemical composition of the essential oils and the isolation of eleven substances from Eupatorium ballotifolium Kunth, Asteraceae. The essential oils were obtained by hydrodistillation, analyzed by GC/MS and evaluated towards the acetylcholinesterase enzyme. The oils yield was of 0.11 percent for the leaves and 0.03 percent for the stems. The main constituents of the oils were the sesquiterpenes β-caryophyllene (24.9 and 22.2 percent), spathulenol (17.7 and 12.4 percent) and epoxy-allo-aromadendrene (23.0 and 23.6 percent). From the hexane extract of the aerial part were isolated a mixture of sitosterol and stigmasterol, its glucosides, and the triterpenes taraxasteryl acetate and taraxasterol, while from the ethanol extract were obtained the flavonoids nepetin and 3-O-glucoside-quercetin. The triterpenes epi-friedelanol and dammara-20,24-dien-3β-ol were obtained from the hexane extract of roots, while the coumarin 11-hydroxy-11,12-di-hydroobliquine was obtained from the ethanol extract. The structures of all compounds were determinate based on spectroscopic methods such as IR, MS and ¹H and 13C NMR.