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1.
Toxicol Lett ; 320: 64-72, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31794810

RESUMO

Oxime-based acetylcholinesterase reactivators (briefly oximes) regenerate organophosphate-inactivated acetylcholinesterase and restore its function. Poor blood-brain-barrier passage and fast elimination from blood limit their actual use in treatment of patients exposed to organophosphates. Previous in vitro results implicated further testing of cucurbit[7]uril as a delivery vehicle for bisquaternary oximes. The present paper focuses on cell toxicity, in vivo safety and influence of cucurbit[7]uril on oxime pharmacokinetics and pharmacodynamics. Neither the K027 nor the complex caused any cell toxicity, changes in blood biochemistry or hepato- or nephrotoxicity in tested concentrations. The encapsulation of K027 increased and accelerated the blood-brain-barrier penetration. The peripheral oxime exposure also increased, supporting the suggestion that cucurbit[7]uril protects the circulating oxime from rapid renal clearance. Contrary to the comparable in vitro reactivation power of K027 and the encapsulated K027, we failed to confirm this in vivo. In theory, this might result from the non-specific binding of molecules to the cucurbit[7]uril or the interaction of K027 with cucurbit[7]uril being too strong for acetylcholinesterase reactivation. Precise explanation requires additional in silico, in vitro and also in vivo experiments.


Assuntos
Acetilcolinesterase/sangue , Acetilcolinesterase/metabolismo , Encéfalo/efeitos dos fármacos , Hidrocarbonetos Aromáticos com Pontes/farmacocinética , Reativadores da Colinesterase/farmacocinética , Eritrócitos/efeitos dos fármacos , Imidazóis/farmacocinética , Oximas/farmacocinética , Compostos de Piridínio/farmacocinética , Células A549 , Animais , Encéfalo/enzimologia , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Reativadores da Colinesterase/administração & dosagem , Reativadores da Colinesterase/toxicidade , Relação Dose-Resposta a Droga , Eritrócitos/enzimologia , Feminino , Proteínas Ligadas por GPI/sangue , Proteínas Ligadas por GPI/metabolismo , Células Hep G2 , Humanos , Imidazóis/administração & dosagem , Imidazóis/toxicidade , Injeções Intramusculares , Masculino , Dose Máxima Tolerável , Camundongos Endogâmicos ICR , Oximas/administração & dosagem , Oximas/toxicidade , Compostos de Piridínio/administração & dosagem , Compostos de Piridínio/toxicidade , Medição de Risco , Distribuição Tecidual
2.
J Environ Public Health ; 2019: 3084501, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31611921

RESUMO

Biomonitoring of pesticides exposure has currently become a matter of great public concern due to the potential health effects of pesticides. This study assessed levels of acetylcholinesterase (AChE) inhibition and associated health effects in uncontrolled smallholder farming systems in rural Tanzania. A cross-sectional study was conducted of 90 exposed farmers and 61 nonexposed controls from horticultural zones. A structured questionnaire was administered, and a capillary blood sample of 10 µl was used to measure AChE activity using an Erythrocyte Acetylcholinesterase Test Mate Photometric Analyzer kit (Model 400). A multiple logistic regression model was used to investigate determinants of pesticide exposure. The study revealed that smallholder farmers are occupationally exposed to pesticides. Exposed farmers had significantly lower AChE levels. The use of personal protective equipment (PPE) did not significantly reduce the likelihood of AChE inhibition. Women, younger and older farmers, and underweight, overweight, and obese farmers were at increased risk of AChE inhibition. Increase in age (10 years) increased likelihood of AChE inhibition by 6.7%, while decrease in BMI increased likelihood of AChE inhibition by 86.7% while increased pesticides contact hours increased risk of having lower AChE at about 3 times. The number of exposure symptoms (14.10 ± 7.70) was higher in exposed farmers than unexposed. Self-reported symptoms are confirmed to correlate to lower AChE. Prevalence of tiredness (71.6% against 15.5%), fatigue (64.8% against 27.6%), soreness in joints (59.1% against 20.7%), thirst (52.3% against 12.1%), skin irritation (52.1% against 17.2%), salivation and abdominal pain (50% against 8.6% and 31.0%, respectively), muscle weakness (47.7% against 24.1%), and memory loss (47.7% against and 29.3%) differed significantly between exposed and control. This study provides useful information regarding the level of occupational and environmental exposure to pesticides in smallholder horticultural production systems. Pesticides use needs to be controlled at farm level by developing pesticides monitoring and surveillance systems.


Assuntos
Acetilcolinesterase/sangue , Fazendeiros/estatística & dados numéricos , Exposição Ocupacional/estatística & dados numéricos , Praguicidas , Adulto , Doenças dos Trabalhadores Agrícolas/induzido quimicamente , Doenças dos Trabalhadores Agrícolas/enzimologia , Doenças dos Trabalhadores Agrícolas/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Equipamento de Proteção Individual/estatística & dados numéricos , Praguicidas/efeitos adversos , Praguicidas/análise , Prevalência , Fatores de Risco , População Rural , Autorrelato , Tanzânia
3.
Mutat Res ; 843: 52-56, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31421739

RESUMO

Exposure to pesticides leads to complex, long-lasting adverse effects on human health, and poses a substantial risk to those living in areas devoted to agriculture. Children are particularly vulnerable to the pesticide exposure, due to the developmental, dietary and physiological factors. Small body mass and typical exploratory behavior result in increased risk of intoxication. Thus, even exposure to low concentrations of pesticides, if of sufficient duration, may lead to permanent health disorders and limit their harmonious development. In this study 108 children, living in areas of an intense pesticide use and a control group (n = 92) of children from an agrotouristic area were investigated, whether DNA damage increased due to prolonged pesticide exposure. A presence of DNA breaks and oxidative damage to DNA bases, characterized as Fpg-sensitive sites, were detected by comet assay. Micronuclei (MN) formation was evaluated by cytokinesis-block MN assay. The exposure of children to pesticides resulted in increased number of MN in peripheral blood lymphocytes (P = 0.016), increased DNA strand breaks level (P = 0.002) and oxidative damage to DNA (P < 0.001). Negative correlation was demonstrated between the level of DNA strand breaks and acetylcholinesterase (AChE) activity in exposed group. In conclusion, despite just environmental pesticide exposure in the test group of children, significant biological effects were detected.


Assuntos
Dano ao DNA , Exposição Ambiental , Praguicidas/toxicidade , Acetilcolinesterase/sangue , Monitoramento Biológico/métodos , Criança , Inibidores da Colinesterase/toxicidade , Ensaio Cometa , DNA/sangue , DNA/efeitos dos fármacos , Quebras de DNA , DNA-Formamidopirimidina Glicosilase/farmacologia , Feminino , Contaminação de Alimentos , Guanina/análogos & derivados , Guanina/sangue , Humanos , Masculino , Testes para Micronúcleos , Pais , Polônia , População Rural
4.
Artigo em Inglês | MEDLINE | ID: mdl-31422162

RESUMO

Deltamethrin (DMN) exposure causes severe damage to the gill and liver tissues of aquatic organisms, as well as neurotoxic effects and metabolic disorders. The goal of the present study was to assess the impacts of DMN toxicity on blood biochemistry, malondialdehyde (MDA) levels, catalase (CAT) levels, behavior disorder, acetylcholinesterase (AChE) activity, histopathology and 8-hydroxy-2-deoxyguanosine (8 OHdG) of brown trout (Salmo trutta fario). Acute concentrations (1.0 and 2.0µg/L) of DMN caused behavioral disorder such as rapid swimming, loss of balance, aggressiveness and increasing in the surface activity and inactivity in brown trout. A significant increase in malondialdehyde (MDA), aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels, and a significant decrease in CAT, AChE, blood albumin, and blood total protein content were observed. Histopathologically, both doses of DMN have caused steatosis, necrosis, and degeneration in hepatocytes and hyperemia in the liver. Also, they led to inflammation, adhesion and fusion depending on severe hyperplasia in secondary lamellae, hyperemia and lamellar edema in gill tissues when compared to control group. Additionally, 8-hydroxy-2-deoxyguanosine (8 OHdG) levels at 2.0 µg/L dose of DMN in liver tissues were more severe according to 1.0 µg/L dose of DMN. Finally, different concentrations of DMN led to changes of the histopathology, 8OHdG, the CAT levels, plasma AChE activity, and the serum metabolites, as well as behavioral disorder in brown trout.


Assuntos
Brânquias/metabolismo , Fígado/metabolismo , Nitrilos/toxicidade , Piretrinas/toxicidade , Truta/metabolismo , Poluentes Químicos da Água/toxicidade , Acetilcolinesterase/sangue , Animais , Catalase/sangue , Malondialdeído/sangue , Estresse Oxidativo
5.
Exp Parasitol ; 205: 107735, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31381870

RESUMO

Two experiments were performed to determine whether oral administration of copper oxide capsules controlled helminthic infections in Lacaune sheep without acute collateral effects on animal health. In experiment 1, 48 multiparous lactating sheep (60.1 ±â€¯8.5 kg) were stratified according to initial number of eggs (Haemonchus contortus) per gram of feces (EPG) and were assigned randomly to 1 of two treatments (24 sheep/treatment): no oral administration (control) or oral administration of two copper capsules (treated; approximately 58 mg copper/kg body weight). Blood and fecal samples were collected on days 0, 15 and 45. Animals treated with copper capsules showed lower of EPG, eosinophils, acetylcholinesterase (AChE) in whole blood, and lower butyrylcholinesterase (BChE) activity in serum. Treated sheep had higher erythrocyte numbers, hemoglobin concentrations, hematocrit, and lymphocyte numbers. In experiment 2, 12 male lambs negative for helminths and coccidia were assigned randomly to one of two treatments (six lambs/treatment): control or treated (one copper capsule; approximately 58 mg copper/kg body weight); the experiment was designed to determine whether the results of experiment 1 were due to treatment or parasitism. Blood samples were collected on days 0, 5, 10 and 15 and fecal samples were collected on days 0, 7 and 15. Treated animals showed greater concentrations of lymphocytes; however, treatment had no effect on other hemogram variables, AChE and BChE activities, or levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, creatinine, urea, albumin, total protein, and reactive oxygen species. These data suggest that copper capsules in dairy sheep efficiently controlled H. contortus infections. Treatment was not harmful to lambs during the first 15 days, i.e. there were no signs of acute toxicity.


Assuntos
Cobre/administração & dosagem , Hemoncose/veterinária , Helmintíase Animal/tratamento farmacológico , Lactação , Doenças dos Ovinos/tratamento farmacológico , Acetilcolinesterase/sangue , Administração Oral , Animais , Butirilcolinesterase/sangue , Cápsulas , Cobre/uso terapêutico , Indústria de Laticínios , Resíduos de Drogas , Eosinófilos/efeitos dos fármacos , Contagem de Eritrócitos/veterinária , Fezes/parasitologia , Feminino , Hemoncose/tratamento farmacológico , Hemoncose/prevenção & controle , Helmintíase Animal/sangue , Helmintíase Animal/prevenção & controle , Hematócrito/veterinária , Hemoglobinas/análise , Contagem de Linfócitos/veterinária , Masculino , Leite/química , Contagem de Ovos de Parasitas/veterinária , Paridade , Distribuição Aleatória , Ovinos , Doenças dos Ovinos/sangue , Doenças dos Ovinos/parasitologia , Doenças dos Ovinos/prevenção & controle
6.
PLoS One ; 14(7): e0219598, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31318899

RESUMO

AIMS: Pathophysiology of reflex syncope is not fully understood but a vagal overactivity might be involved in this syncope. Previously, overexpression of muscarinic M2 receptors and acetylcholinesterase was found in particular in the heart and in lymphocytes of rabbits with vagal overactivity as well as in hearts of Sudden Infant Death Syndromes. The aim of this present study was to look at M2 receptor expression in blood of patients with reflex syncope. The second objective was to measure acetylcholinesterase expression in these patients. METHODS AND RESULTS: 136 subjects were enrolled. This monocenter study pooled 45 adults exhibiting recurrent reflex syncope compared with 32 healthy adult volunteers (18-50 years) and 38 children exhibiting reflex syncope requiring hospitalization compared with 21 controls (1-17 years). One blood sample was taken from each subject and blood mRNA expression of M2 receptors was assessed by qRT-PCR. Taking into account the non-symmetric distributions of values in both groups, statistical interferences were assessed using bayesian techniques. A M2 receptor overexpression was observed in adult and pediatric patients compared to controls. The medians [q1;q3] were 0.9 [0.3;1.9] in patients versus 0.2 [0.1;1.0] in controls; the probability that M2 receptor expression was higher in patients than in controls (Pr[patients>controls]) was estimated at 0.99. Acetylcholinesterase expression was also increased 0.7 [0.4;1.6] in patients versus 0.4 [0.2;1.1] in controls; the probability that acetylcholinesterase expression was higher in patients than in controls (Pr[patients>controls]) was estimated at 0.97. Both in adults and children, the expression ratio of M2 receptors over acetylcholinesterase was greater in the patient group compared with the control group. CONCLUSION: M2 receptor overexpression has been detected in the blood of both, adults and children, exhibiting reflex syncope. As in our experimental model, i.e. rabbits with vagal overactivity, acetylcholinesterase overexpression was associated with M2 receptor overexpression. For the first time, biological abnormalities are identified in vagal syncope in which only clinical signs are, so far, taken into account for differential diagnosis and therapeutic management. Further work will be needed to validate potential biomarkers of risk or severity associated with the cholinergic system.


Assuntos
Receptores Muscarínicos/sangue , Síncope Vasovagal/sangue , Acetilcolinesterase/sangue , Acetilcolinesterase/genética , Adulto , Criança , Feminino , Humanos , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Muscarínicos/genética
7.
Int J Hyg Environ Health ; 222(7): 981-990, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31202795

RESUMO

BACKGROUND: The cholinergic system has an important role in mood regulation. Cholinesterase inhibitor pesticides (e.g. organophosphates) appear to increase depression and anxiety symptoms in the few existing animal and human studies. Human studies have not described such associations using biomarkers of exposure and studies among children are needed. METHODS: We studied 529 adolescents (ages 11-17y) in agricultural communities in the Ecuadorian Andes (ESPINA study). Acetylcholinesterase (AChE) activity was measured in a finger-stick sample. Anxiety and depression symptoms were assessed using the CDI-2 and MASC-2 (greater scores reflect greater internalizing symptoms). Models adjusted for age, gender, hemoglobin, income among others. RESULTS: The median age was 14.38y and 51% were female. The mean (SD) of the following parameters were: AChE 3.7 U/mL (0.55), depression T-score 53.0 (9.4) and anxiety T-score: 57.6 (9.8). Lower AChE activity (reflecting greater cholinesterase inhibitor exposure) was associated with higher depression symptoms (difference per SD decrease of AChE [ß [95% CI:]]: 1.09 [0.02, 2.16]), was stronger among girls (ß = 1.61) than boys (ß = 0.69), and among younger (<14.38y, ß = 1.61) vs. older children (ß = 0.57). The associations were strongest among girls <14.38y (ß = 3.30 [0.54, 6.05], OR for elevated symptoms per SD decrease in AChE = 2.58 [1.26, 5.27]). No associations were observed with anxiety scores. Analyses of AChE change between 2008 and 2016 concurred with these findings. DISCUSSION: We observed associations between a biomarker of pesticide exposure and children's depression symptoms. Lower AChE activity may create risk for depression in teenagers, particularly among girls during early adolescence.


Assuntos
Acetilcolinesterase/sangue , Ansiedade/enzimologia , Inibidores da Colinesterase , Depressão/enzimologia , Exposição Ambiental , Praguicidas , Adolescente , Biomarcadores/sangue , Criança , Equador , Feminino , Horticultura , Humanos , Masculino
8.
Environ Toxicol Chem ; 38(8): 1692-1700, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31063226

RESUMO

Plasma cholinesterase activity is a biomarker sensitive to the effect of organophosphate and carbamate pesticides, and its enzymatic levels have been previously unknown for most of the wild birds analyzed in the present study. Our objectives were to establish plasma acetylcholinesterase levels in songbirds of 2 undisturbed sites in the central Monte Desert (Argentina). We also examined the influence on cholinesterase activity of age, sex, body condition, feeding and migratory habits, and species. One hundred and sixty-five wild birds belonging to 26 species were studied. The values obtained for acetylcholinesterase activity provide a good estimate of the normal values in free-living individuals of the species Zonotrichia capensis, Molothrus bonariensis, Passer domesticus, Diuca diuca, Poospiza ornata, Saltator aurantiirostris, Gryseotyrannus aurantioatrocristatus, and Columbina picui, with interspecies differences. The median enzymatic levels ± standard error of the mean ranged from 546.31 ± 17.97 µmol min-1 L-1 in P. domesticus to 3439.90 ± 173.92 µmol min-1 L-1 in Tyrannus melancholicus. No significant differences were detected between different sexes or ages. Birds that migrate (which are also insectivores) showed higher levels of cholinesterase than residents (mainly granivores). It is recommended that in cases of bird poisoning, plasma cholinesterase activity can be used as a diagnostic tool only if pre-exposure levels obtained in the same species are available, and ideally evaluated in individuals from the same biogeographical region. Environ Toxicol Chem 2019;38:1692-1700. © 2019 SETAC.


Assuntos
Acetilcolinesterase/sangue , Animais Selvagens/sangue , Monitoramento Ambiental/métodos , Poluentes Ambientais/toxicidade , Florestas , Aves Canoras/sangue , Animais , Argentina , Biomarcadores/sangue , Carbamatos/toxicidade , Feminino , Masculino , Organofosfatos/toxicidade , Praguicidas/toxicidade , Especificidade da Espécie
9.
Neurotoxicology ; 74: 1-6, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31077682

RESUMO

BACKGROUND: Exposure to environmental chemicals, including organophosphorus pesticides, is associated with behavioral disorders such as attention deficit hyperactivity disorder (ADHD). However, the impact of occupational pesticide exposure on ADHD development in adolescents has not been examined. OBJECTIVE: We examined the association between exposure to chlorpyrifos and ADHD symptoms among adolescents in Egypt. METHODS: Adolescent pesticide applicators and non-applicators, 12-21 years old, participated in a 10-month longitudinal study examining health effects from pesticide exposure. Repeated urine and blood samples were collected at various time points during the 10-months to assess biomarkers of chlorpyrifos exposure (urinary trichloro-2-pyridinol or TCPy) and effect (blood acetyl cholinesterase activity and butyryl cholinesterase activity). Parents from a subset of the cohort (N = 64) completed the Short Form of Conners' Parent Rating Scale - Revised. Poisson regressions were used to examine the associations between the number of ADHD symptoms and occupation and biomarkers. RESULTS: Pesticide applicators had significantly more symptoms of ADHD than participants in the non-applicator group. Urinary TCPy levels were associated with increased symptoms, demonstrating a dose-response effect. Applicators with ADHD reported applying pesticides for more hours during the application season and had greater cumulative TCPy levels than participants without ADHD. One fourth of all applicators met the criteria for an ADHD diagnosis (having 6 or more reported symptoms). CONCLUSIONS: This study provides preliminary evidence of an association between occupational exposure to chlorpyrifos and ADHD symptoms among adolescent pesticide applicators in spite of its limited small sample size. There is a critical need to investigate the susceptibility of children and adolescents to repeated occupational and environmental exposures to pesticides because the developing brain may be uniquely sensitive to the neurotoxic effects of these agents.


Assuntos
Doenças dos Trabalhadores Agrícolas/epidemiologia , Doenças dos Trabalhadores Agrícolas/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Clorpirifos/toxicidade , Inseticidas/toxicidade , Exposição Ocupacional/efeitos adversos , Acetilcolinesterase/sangue , Acetilcolinesterase/urina , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Biomarcadores/análise , Criança , Inibidores da Colinesterase/toxicidade , Egito/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Testes Neuropsicológicos , Piridonas/urina , Adulto Jovem
10.
Molecules ; 24(8)2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-31003551

RESUMO

New reliable and robust potentiometric ion-selective electrodes were fabricated using poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT/PSS) as the solid contact between the sensing membrane and electrical substrate for an acetylcholine (ACh) bioassay. A film of PEDOT/PSS was deposited on a solid carbon screen-printed platform made from ceramic substrate. The selective materials used in the ion-selective electrode (ISE) sensor membrane were acetylcholinium tetraphenylborate (ACh/TPB/PEDOT/PSS-ISE) (sensor I) and triacetyl-ß-cyclodextrin (ß-CD/PEDOT/PSS-ISE) (sensor II). The sensors revealed clear enhanced Nernstian response with a cationic slope 56.4 ± 0.6 and 55.3 ± 1.1 mV/decade toward (ACh+) ions over the dynamic linear range 1.0 × 10-6-1 × 10-3 and 2.0 × 10-6-1.0 × 10-3 M at pH 5 with limits of detection 2.0 × 10-7 and 3.2 × 10-7 M for sensors I and II, respectively. The selectivity behavior of both sensors was also tested and the sensors showed a significant high selectivity toward ACh+ over different common organic and inorganic cations. The stability of the potential response for the solid-contact (SC)/ISEs was evaluated using a chronopotentiometric method and compared with that of electrodes prepared without adding the solid-contact material (PEDOT/PSS). Enhanced accuracy, excellent repeatability, good reproducibility, potential stability, and high selectivity and sensitivity were introduced by these cost-effective sensors. The sensors were also used to measure the activity of acetylcholinesterase (AChE). A linear plot between the initial rate of the hydrolysis of ACh+ substrate and enzyme activity held 5.0 × 10-3-5.2 IU∙L-1 of AChE enzyme. Application to acetylcholine determination in human serum was done and the results were compared with the standard colorimetric method.


Assuntos
Acetilcolina/sangue , Acetilcolinesterase/sangue , Técnicas Biossensoriais/métodos , Compostos Bicíclicos Heterocíclicos com Pontes/química , Carbono/química , Neurotransmissores/sangue , Polímeros/química , Poliestirenos/química , Impressão , Análise de Injeção de Fluxo , Humanos , Hidrodinâmica , Hidrólise , Cinética , Potenciometria , Água/química
11.
J Biochem Mol Toxicol ; 33(8): e22341, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30990955

RESUMO

Chlorpyrifos (CPF), an organophosphate insecticide has a wider application throughout the world to protect agricultural crops and vegetables from insects. Polyphenolic compounds are considered as beneficial against toxicities induced by organophosphates. The present study was conducted to understand the neuroprotective role of quercetin in chlorpyrifos-induced apoptotic events in rats. Twenty-four male Sprague Dawley rats weighing 170 to 200 g were divided into four groups viz: Control, chlorpyrifos treated (13.5 mg/kg body wt. alternate day), quercetin treated (50 mg/kg body wt. every day) and combined chlorpyrifos + quercetin treated. All the treatments were carried out for a total duration of 60 days. Protein carbonyl content and acetylcholinesterase activity were estimated in serum along with cerebrum and cerebellum to ascertain neurotoxicity. Further, for appraisal of neurodegeneration as a consequence of apoptosis, protein expressions of Bcl-2, Bax, cytochrome c, caspase-8, and caspase-9 were assessed. The results showed that protein carbonyl contents were markedly increased in both serum and brain tissues (cerebrum and cerebellum) of chlorpyrifos-treated rats when compared with control group and were appreciably improved upon simultaneous supplementation with quercetin. Further, chlorpyrifos treatment revealed a significant decrease in the enzyme activity of acetylcholinesterase in serum as well as in cerebrum and cerebellum, which however was increased upon concomitant treatment with quercetin. In chlorpyrifos-treated animals, we have observed a significant decrease in the protein expression level of Bcl-2, but a remarkable increase in the expression levels of Bax, cytochrome c, caspase-8, and caspase-9 in both cerebrum and cerebellum. Interestingly, when chlorpyrifos-treated animals were supplemented with quercetin, a significant increase in the expression of Bcl-2 and an appreciable decline in the expression levels of Bax, cytochrome c, caspase-8, and caspase-9 was observed. In conclusion, the present study advocates that quercetin may prove to be a useful candidate in containing the oxidative-induced apoptotic events during chlorpyrifos exposure.


Assuntos
Apoptose/efeitos dos fármacos , Clorpirifos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Quercetina/farmacologia , Acetilcolinesterase/sangue , Acetilcolinesterase/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Cerebelo/enzimologia , Inibidores da Colinesterase/toxicidade , Inseticidas/toxicidade , Masculino , Ratos , Ratos Sprague-Dawley
12.
Microb Pathog ; 132: 137-140, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31028864

RESUMO

The role of cholinesterase in inflammatory reactions has been described in several infectious diseases. However, in Brucella spp. this has not yet been studied. Therefore, the objective of this study was to evaluate whether experimental infection by Brucella ovis alters the cholinergic activity in pro- or anti-inflammatory responses to the disease. For the study 48 mice were used, 24 infected by B. ovis and 24 non-infected. We collected samples of whole blood on days 7, 15, 30 and 60 post-infection (PI) by B. ovis. Acetylcholinesterase (AChE) activity in the blood increased on days 15 and 60 PI (P < 0.05). Butyrylcholinesterase (BChE) activity in serum increased on days 7 and 60 PI (P < 0.05). An increase in serum free radical levels occurred on days 7, 15 and 60 PI (P < 0.05), and consequently superoxide dismutase activity increased on day 15 PI (P < 0.05). A reduction in catalase activity occurred when the infection became chronic (60 PI). The increase in AChE and BChE characterized a pro-inflammatory response, since these enzymes regulate levels of acetylcholine (ACh) and butyrylcholine (BuSCh), molecules with anti-inflammatory properties. Therefore, with the increase of cholinesterase activity, there was an extracellular reduction of ACh, an inhibitor of several inflammatory mediators. This proinflammatory response of B. ovis infection leads to oxidative stress, and consequently to cellular damage.


Assuntos
Acetilcolinesterase/metabolismo , Brucella ovis/patogenicidade , Butirilcolinesterase/metabolismo , Colinesterases/metabolismo , Acetilcolina/metabolismo , Acetilcolinesterase/sangue , Animais , Brucelose/sangue , Butirilcolinesterase/sangue , Catalase , Colina/análogos & derivados , Colina/metabolismo , Colinérgicos/farmacologia , Colinesterases/sangue , DNA Bacteriano/análise , Modelos Animais de Doenças , Inflamação , Masculino , Camundongos , Estresse Oxidativo , Espécies Reativas de Oxigênio/sangue , Espécies Reativas de Oxigênio/metabolismo , Soro/enzimologia , Superóxido Dismutase
13.
Artigo em Inglês | MEDLINE | ID: mdl-30813607

RESUMO

This study aims to determine the degree of acetylcholinesterase inhibition and neurological symptoms for each of the psychiatric disorders diagnosed in the farm workers of a rural population in the state of Baja California, Mexico. We conducted a cross-sectional study on 140 agricultural workers (exposed participants). The study was run using the Mini International Neuropsychiatric Interview Diagnostic Test (MINI), a pre-established questionnaire to diagnose the mental state of each agricultural worker. Analysis of enzymatic activity was carried out using the modified Ellman method. The results showed that, among agricultural workers with slightly inhibited enzymatic activity, 25% met the criteria for the diagnosis of major depression with suicidal attitudes, 23.9% with inhibited enzymatic activity showed generalized anxiety, 23.5% showed combined depression⁻anxiety, and 22% met the criteria for major depression and no psychiatric diagnosis disorder. These results suggest the need for the development of effective public-health strategies to inform farm workers about integrated pesticide management in order to prevent serious health complications.


Assuntos
Doenças dos Trabalhadores Agrícolas/epidemiologia , Doenças dos Trabalhadores Agrícolas/etiologia , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia , Exposição Ocupacional/estatística & dados numéricos , Intoxicação por Organofosfatos/complicações , Intoxicação por Organofosfatos/epidemiologia , Acetilcolinesterase/sangue , Adolescente , Adulto , Doenças dos Trabalhadores Agrícolas/diagnóstico , Estudos Transversais , Fazendeiros , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , México/epidemiologia , Pessoa de Meia-Idade , Exposição Ocupacional/análise , Intoxicação por Organofosfatos/diagnóstico , Psicometria/estatística & dados numéricos , População Rural , Adulto Jovem
14.
Parasitol Int ; 71: 11-17, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30849474

RESUMO

Both oxidative stress and alterations in adenosinergic and cholinergic systems participate in initiation and progression of parasitic infectious diseases. Nevertheless, the involvement of these pathways during eimeriosis remains poorly understood. Therefore, the aim of this study was to evaluate the involvement of adenosinergic and cholinergic systems in regulation of inflammatory response and oxidative stress in chicken chicks experimentally infected with Eimeria spp. Two groups were formed for comparison at 3 time points (days 5, 10 and 15) of infection (PI): uninfected (control) and infected. Erythrocyte counts, hematocrit and hemoglobin levels were lower in infected chicks on day 15 post-infection (PI). Total leukocytes, heterophil and lymphocyte counts were higher in infected chicks on days 5 and 10 PI, while eosinophil counts were higher only on day 10 PI. Serum levels of total protein and globulins were higher in infected chicks on days 10 and 15 PI, while triglycerides and cholesterol levels were lower on day 15 PI. Acetylcholinesterase activity in total blood and butyrylcholinesterase activity in serum were higher in infected chicks on day 15 PI, while adenosine deaminase activity was higher on day 10 PI and lower on day 15 PI compared with the respective control. Finally, serum levels of reactive oxygen species and catalase activity in total blood were higher in infected chicks on day 15 PI, while superoxide dismutase activity in total blood was lower at the same time of infection. These data suggest that cholinergic and adenosinergic systems display a pro-inflammatory profile that contributes to impairment of immune and inflammatory responses in a mixed Eimeria infection. Furthermore, oxidative stress may contribute to clinical signs of disease as well as to pathogenesis. In summary, the impairment of immune response and alterations in blood antioxidant/oxidant status contributes to disease pathophysiology.


Assuntos
Acetilcolinesterase/sangue , Adenosina Desaminase/sangue , Butirilcolinesterase/sangue , Coccidiose/veterinária , Eimeria , Estresse Oxidativo , Animais , Catalase/sangue , Galinhas/parasitologia , Coccidiose/fisiopatologia , Inflamação , Oócitos/fisiologia , Doenças das Aves Domésticas/sangue , Doenças das Aves Domésticas/parasitologia , Espécies Reativas de Oxigênio/sangue
15.
Biosens Bioelectron ; 131: 232-236, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30849722

RESUMO

A ratiometric fluorescence probe based on carbon dots (CDs) was developed for discriminative and highly sensitive detection of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity in human whole blood. When o-phenylenediamine (OPD) was oxidized by Cu2+, the product 2,3-diaminophenazine (oxOPD) could effectively quench the fluorescence of CDs at 460 nm due to the inner filter effect and gave rise to a new emission peak at 570 nm. The AChE or BChE catalyzed hydrolysis reaction of acetylthiocholine or butyrylthiocholine to generate thiocholine, whose sulfhydryl group strongly captured Cu2+ to inhibit the oxidization of OPD, thus effectively preserving the natural fluorescence emission of CDs. The resulting fluorescence intensity ratio served as the signal output of the probe for cholinesterases (ChEs) activity sensing. The activities of AChE and BChE were determined to range from 0.2 to 14.0 U L-1 and from 0.1 to 5.0 U L-1, with detection limits of 0.1 U L-1 and 0.04 U L-1, respectively. Additionally, the IC50 of tacrine and ethopropazine for the inhibition of AChE and BChE were estimated to be 29.8 nM and 132.6 nM, respectively. Moreover, the probe was successfully applied to the discriminative determination of AChE and BChE in human whole blood without any pretreatment. These results suggested that the proposed strategy provided a discriminative, sensitive and robust analytical platform for ChEs clinical diagnostics and drug screening.


Assuntos
Acetilcolinesterase/sangue , Técnicas Biossensoriais , Butirilcolinesterase/sangue , Carbono/química , Catálise , Inibidores da Colinesterase/química , Cobre/química , Corantes Fluorescentes/química , Humanos , Limite de Detecção , Fenazinas/química , Fenilenodiaminas/química
16.
Ecotoxicol Environ Saf ; 172: 246-254, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30711859

RESUMO

Free-ranging animals are often used as bioindicators of both short- and long-term changes in ecosystem health, mainly to detect the presence and effects of contaminants. Birds, and gulls in particular, have been used as bioindicators over a broad range of marine and terrestrial ecosystems. In this study, we standardise the conditions for the use of a suite of biochemical markers in non-destructive matrices of Lesser Black-backed Gull (Larus fuscus) to facilitate future biomonitoring of marine and terrestrial contaminants. We characterized cholinesterase (ChE) in plasma and optimized assay conditions for ChE activity as a marker of neurotoxic damage. Moreover, we quantified variation in activity of ChE, lactate dehydrogenase (LDH), glutathione-S-transferase (GST) and catalase (CAT) as well as variation ranges of lipid peroxidation (LPO), in free-ranging adults and captive chicks. The main ChE form present in plasma of both adults and chicks was butyrylcholinesterase (BChE) followed by acetylcholinesterase (AChE), whose relative proportion in plasma tended to decrease with increased chick age. LPO levels and GST activity in blood cells (BCs) decreased significantly with increasing chick age, while BChE and LDH activity in plasma were not age-dependent. CAT in BCs tended to decline non-significantly in older chicks. Results of this study underscore the importance of standardising assay conditions and assessing intrinsic baseline variation in biochemical markers, before biochemical quantification. Data presented here provide a foundation for future use of BChE and LDH activity in plasma, as well as oxidative stress markers (LPO, CAT and GST) in BCs, to monitor environmental stress effects in Lesser Black-backed gulls.


Assuntos
Charadriiformes/metabolismo , Monitoramento Ambiental/métodos , Acetilcolinesterase/sangue , Fatores Etários , Animais , Bioensaio , Biomarcadores/metabolismo , Butirilcolinesterase/sangue , Catalase/metabolismo , Feminino , Glutationa Transferase/metabolismo , L-Lactato Desidrogenase/metabolismo , Peroxidação de Lipídeos , Masculino
17.
Clin Toxicol (Phila) ; 57(5): 343-349, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30307341

RESUMO

BACKGROUND: In a military or terrorist scenario, combination of organophosphorus compounds (OP) poisoning with physical trauma requiring surgical treatment and thus general anaesthesia are possible. Previous in vitro studies showed an altered potency of relevant anaesthetics during cholinergic crisis. Hence, it is not clear, which anaesthetics are suitable to achieve the necessary stage of surgical anaesthesia in OP poisoning. METHODS: In the present study, different anaesthetic regimens (ketamine-midazolam, propofol-fentanyl, thiopental-fentanyl), relevant in military emergency medicine, were examined in soman-poisoned rats. Clinical signs and cardiovascular variables were recorded continuously. Blood samples for acetylcholinesterase (AChE) activity were drawn. After euthanasia or death of the animals, brain and diaphragm were collected for cholinesterase assays. RESULTS: Propofol-fentanyl and thiopental-fentanyl resulted in surgical anaesthesia throughout the experiments. With ketamine-midazolam, surgical anaesthesia without respiratory impairment could not be achieved in pilot experiments (no soman challenge) and was therefore not included in the study. Soman-poisoned and control animals required a comparable amount of propofol-fentanyl or thiopental-fentanyl. In combination with atropine, significantly less propofol was needed. Survival rate was higher with thiopental compared to propofol. Atropine improved survival in both groups. Blood and tissue AChE activities were strongly inhibited after soman administration with and without atropine treatment. DISCUSSION: The current in vivo study did not confirm concerns of altered potency of existing anaesthetic protocols for the application of propofol or thiopental with fentanyl due to soman poisoning. Despite severe cholinergic crisis, sufficient anaesthetic depth could be achieved in all animals. CONCLUSION: Further experiments in in vivo models closer to human pharmaco- and toxicokinetics (e.g., swine) are required for confirmation of the initial findings and for improving extrapolation to humans.


Assuntos
Analgésicos Opioides/farmacologia , Anestesia Intravenosa , Anestésicos Intravenosos/farmacologia , Inibidores da Colinesterase , Estado de Consciência/efeitos dos fármacos , Fentanila/farmacologia , Intoxicação por Organofosfatos/enzimologia , Propofol/farmacologia , Soman , Tiopental/farmacologia , Acetilcolinesterase/sangue , Animais , Biomarcadores/sangue , Modelos Animais de Doenças , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/sangue , Masculino , Intoxicação por Organofosfatos/fisiopatologia , Ratos Wistar
18.
Int J Obes (Lond) ; 43(2): 297-305, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29491490

RESUMO

BACKGROUND: Impaired sympathetic/parasympathetic response, expressed by elevated Acetylcholinesterase (AChE) is associated with obesity, metabolic syndrome and inflammation. However, the association between morbid obesity and AChE and the changes in cholinergic tone following bariatric laparoscopic sleeve gastrectomy (LSG) surgery-induced weight reduction were never analyzed. METHODS: Two studies are presented; the first (the "apparently healthy cohort") was a cross-sectional study and the second (the "LSG cohort") was a prospective-cohort study with 12 months of follow-up. The "apparently healthy cohort" included 1450 apparently healthy participants who volunteered to the Tel-Aviv Medical Center Inflammation Survey (TAMCIS) during a routine annual checkup visit. The "LSG cohort" included 77 morbid obese patients before and at 3, 6, and 12 months following LSG surgery. Main outcomes included anthropometric measurements, Hemoglobin A1c (HbA1C), serum AChE, insulin test and Homeostasis Model Assessment (HOMA). RESULTS: Among the TAMCIS participants, serum AChE activity increased with BMI in a dose-dependent manner until it reached a peak level at BMI of 30-35 kg/m², followed by a plateau. Following LSG, a significant decrease in AChE activity between baseline and 12 months post-surgery was found for men, but not for women (-122.2 ± 135.3, P < 0.001 vs. -21.8 ± 120.5, P = 0.258 nmol substrate hydrolyzed/min per ml, respectively). The reduction in AChE activity was negatively correlated with %excess weight loss (EWL) and positively correlated with %body fat reduction at 12 months post-surgery among women (r = -0.329, P = 0.034 and r = 0.350, P = 0.023, respectively). In men, AChE activity reduction was positively correlated with the HOMA reduction (r = 0.358, P = 0.048). CONCLUSIONS: Obesity-related AChE resistance phenotype may be reversed following LSG and correlates with metabolic outcomes. Further long-term studies will be needed to validate and evaluate the beneficial effect of AChE reduction post bariatric surgery.


Assuntos
Acetilcolinesterase/sangue , Gastrectomia , Obesidade/enzimologia , Obesidade/cirurgia , Adulto , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
19.
Ecotoxicol Environ Saf ; 167: 60-68, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30296697

RESUMO

Available data regarding Imidacloprid (IMI) insecticide hazards to birds are still being scare. Our study aimed to investigate toxic impacts of IMI oral gavage by different dose levels on the brain and liver of Rock pigeon (Columba livia domestica). Forty mature male birds were divided equally into four groups. A control group (C) was orally dosed Mazola corn oil and other three groups; the low dose (LD), the medium dose (MD), and the high dose (HD) groups were orally dosed IMI in Mazola corn oil by three dose levels corresponding to 1/15th, 1/10th, 1/5th IMI oral LD50 respectively. IMI exposure induced a significant decrease in serum levels of glutathione (GSH), superoxide dismutase (SOD) enzyme activity. On the other hand; malondialdehyde (MDA) levels were elevated. The levels of serum total protein, albumin, globulin, and A/G ratio showed a non-significant changes in all IMI dosed groups except levels of total protein in the HD IMI dosed group showed a significant decrease compared to the C group. Serum levels of alanine aminotransferase (ALT), lactate dehydrogenase (LDH), uric acid, plasma tumor necrosis factor α (TNFα) and plasma acetylcholinesterase (AChEs) enzyme activities showed a significant dose related increase in all IMI exposed groups compared to the C group; except the levels of ALT, LDH, and uric acid showed a non significant decrease in the LD IMI dosed group only. Residues of IMI were detected in the pectoral muscles, liver, brain, and kidney of all dosed rock pigeon. Moreover; pectoral muscles were the highest tissue for IMI residues detection. This is the first study reports accumulation of IMI in tissues other than crop, liver, and kidney of rock pigeon including brain and muscles. Moreover, the examined brain and liver tissues of all IMI dosed groups showed dosed related alterations in their structural and ultra-structural morphology. It is concluded that IMI oral administration to pigeon induced oxidative stress and detrimental effects in brain and liver of exposed pigeons. Additionally; IMI bio-accumulated in different organs being muscles is the highest tissues for IMI residues, thus monitoring of IMI residues in food is very essential.


Assuntos
Encéfalo/efeitos dos fármacos , Columbidae , Inseticidas/toxicidade , Fígado/efeitos dos fármacos , Neonicotinoides/toxicidade , Nitrocompostos/toxicidade , Acetilcolinesterase/sangue , Administração Oral , Animais , Biomarcadores/sangue , Encéfalo/metabolismo , Relação Dose-Resposta a Droga , Rim/efeitos dos fármacos , Rim/metabolismo , Dose Letal Mediana , Fígado/metabolismo , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Estresse Oxidativo , Resíduos de Praguicidas/toxicidade , Testes de Toxicidade , Testes de Toxicidade Subcrônica
20.
Neurobiol Aging ; 73: 21-29, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30316049

RESUMO

Cerebral ß-amyloid (cAß) deposition and cholinergic dysfunction have been considered as major pathological and functional hallmarks of Alzheimer's disease (AD). Acetylcholinesterase (AChE) is one of the major cholinergic enzymes, and there is no report to show the relationship between cAß accumulation and peripheral AChE alteration in early stage of AD pathogenesis. Recent studies demonstrate that cAß starts to deposit 15-20 years ahead of symptomatic appearance and this preclinical AD is important for early diagnosis of disease. In this study, we investigated the link between cAß deposition and the peripheral AChE in cognitively normal (CN) individuals. A total of 407 individuals who underwent Pittsburgh compound B (PiB)-positron emission tomography participated in our study. Lower levels of plasma AChE and its enzymatic activity were detected in CN individuals with cAß deposition than in those without cAß. Plasma AChE levels and enzymatic activity were negatively correlated with the degree of cAß deposition. Our results suggest that blood AChE can be used as a potential blood biomarker for the prediction of cAß deposition in CN individuals.


Assuntos
Acetilcolinesterase/sangue , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Diagnóstico Precoce , Idoso , Doença de Alzheimer/psicologia , Compostos de Anilina , Biomarcadores/sangue , Encéfalo/diagnóstico por imagem , Cognição , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Tiazóis
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