ABSTRACT
Background Emerging evidence has shown the damage of air pollution and the benefits of physical activity to human health, and the effects of air pollution and physical activity on the nervous system need more research. Objective To explore the effects of short-term air pollution exposure and physical activity on neural damage biomarkers in healthy elderly. Methods Using a design of panel study, physically and mentally healthy retired employees were recruited from Xinxiang Medical University, and were followed up five times regularly from December 2018 to April 2019. The demographic characteristics and physical activity information were obtained by questionnaire, and the weekly physical activity level was calculated according to intensity and duration of physical activity. Biomarkers of neural damage in serum were measured, including brain-derived neurotrophic factor (BDNF), neurofilament light chain (NF-L), neuron specific enolase (NSE), protein gene product 9.5 (PGP9.5), and S100 calcium-binding protein B (S100B). Air pollution data (including PM2.5, PM10, O3, SO2, CO, and NO2) of the follow-up period were collected. Generalized estimation equation was used to analyze the association of air pollution concentration and physical activity level with the concentration of neural damage biomarkers. Results A total of 29 volunteers were included in the study, with an average age of (63.5±5.9) years; there were 11 men accounting for 37.93%; more than half of them (62.07%) received above junior middle school education; the mean physical activity level was (80.23±54.51) MET-h·week−1. The daily average concentrations of PM2.5, PM10, O3, SO2, CO, and NO2 during the study period were (68.27±60.98) μg·m−3, (130.57±58.71) μg·m−3, (36.86±13.89) μg·m−3, (17.86±10.59) μg·m−3, (4.94±1.34) mg·m−3, and (50.83±8.03) μg·m−3, respectively. The average serum concentrations of BDNF, NF-L, NSE, PGP9.5, and S100B were (139.12±46.71) μg·L−1, (402.60±183.31) ng·L−1, (11.26±10.32) ng·L−1, (14.32±13.57) ng·L−1, and (127.57±41.74) ng·L−1, respectively. The results of generalized estimation equation showed that a higher concentration of PM2.5 or O3 was associated with increased serum NSE (OR=1.359, 95%CI: 1.224-1.509, P<0.001; OR=1.286, 95%CI: 1.076-1.537, P=0.006), while a higher concentration of NO2 was associated with decreased serum NSE (OR=0.692, 95%CI: 0.549-0.873, P=0.002); a higher concentration of O3 or SO2 was related to the reduction of serum NF-L concentration (OR=0.855, 95%CI: 0.740-0.989, P=0.035; OR=0.813, 95%CI: 0.700-0.946, P=0.007); a higher concentration of NO2 was associated with decreased PGP9.5 in serum (OR=0.866, 95%CI: 0.777-0.965, P=0.009); a higher level of physical activity was associated with increased serum S100B (OR=1.038, 95%CI: 1.003-1.074, P=0.034); and no significant association of physical activity level or air pollution with BDNF (P>0.05). Conclusion Acute exposure to air pollution and high-level physical activity might affect the neural damage of elderly populations. Specifically, particulate matter (PM2.5) could increase NSE, while gaseous pollutants (O3, NO2, and SO2) could decrease NF-L and PGP9.5.
ABSTRACT
O trato gastrointestinal (TGI) é a principal rota de exposição ao fluoreto (F) e o seu mais importante sítio de absorção. Acredita-se que a toxicidade do F comprometa a fisiologia do intestino, devido à relevante sintomatologia gastrointestinal relatada em consequência da exposição excessiva ao F. A função intestinal é controlada por uma complexa rede neuronal interligada e incorporada à parede deste órgão, denominada Sistema Nervoso Entérico (SNE). Embora os efeitos tóxicos do F sobre o Sistema Nervoso Central sejam descritos na literatura, não há estudos relacionados à sua toxicidade sobre o SNE. Neste estudo realizado em ratos, foi avaliado o efeito da exposição aguda ou crônica ao F, sobre a população geral de neurônios entéricos e sobre as subpopulações que expressam os principais neurotransmissores entéricos: Acetilcolina (ACh), Óxido Nítrico (NO), Peptídeo Vasoativo Intestinal (VIP), Peptídeo Relacionado ao Gene da Calcitonina (CGRP) e Substância P (SP). Os animais foram divididos em 5 grupos: 3 destinados à exposição crônica (0 ppm, 10 ppm ou 50 ppm de F na água de beber) e 2 à exposição aguda (0 ou 25 mgF/Kg por gavagem gástrica). Foram coletados os 3 segmentos do intestino delgado (duodeno, jejuno e íleo) e processados para a detecção da HuC/D, ChAT, nNOS, VIP, CGRP e SP, através de técnicas de imunofluorescência, no plexo mioentérico. Foram obtidas imagens para a realização da análise quantitativa dos neurônios da população geral (HuC/D) e nitrérgicos (imunorreativos à nNOS); e morfométrica dos neurônios imunorreativos à HuC/D ou nNOS; e das varicosidades imunorreativas à ChAT, VIP, CGRP ou SP. Amostras dos 3 segmentos intestinais foram preparadas e coradas em Hematoxilina e Eosina para análise histológica da morfologia básica. O segmento intestinal considerado mais afetado na análise morfométrica da população geral de neurônios, o duodeno, foi selecionado para a realização da análise proteômica, com o objetivo de oferecer o seu perfil proteico...
The gastrointestinal tract (GIT) is the main route of fluoride (F) exposure, and the most important site of its absorption. It is believed that F toxicity compromises the intestine physiology, due to the relevant gastrointestinal symptomatology reported in consequence to excessive exposure. The intestinal function is controlled by a complex neuronal net, which is interconnected and embedded in the wall of this organ, named Enteric Nervous System (ENS). Although the toxic effects of F on the Central Nervous system are described in the literature, there are no studies related to its toxicity on the ENS. Therefore, in this study performed in rats, the effects of chronic and acute F exposure were evaluated, on the general population of enteric neurons and on the subpopulations that express the main enteric neurotransmitters: Acetylcholine (Ach), Nitric Oxide (NO), Vasoactive Intestinal Peptide (VIP), Calcitonin gene related peptide (CGRP), and Substance P (SP). The animals were divided into 5 groups: 3 designed to the chronic exposure (0 ppm, 10 ppm ou 50 ppm de F in the drinking water) and 2 to the acute exposure (0 ou 25 mgF/Kg - gastric gavage). Three intestinal segments were collected (duodenum, jejunum, and ileum) and processed for the immunofluorescence techniques to detect HuC/D, ChAT, nNOS, VIP, CGRP and SP, on the myenteric plexus. Images were obtained for the quantitative analysis of the general population of neurons (HuC/D immunoreactive) and the nitrergic neurons (nNOS immunoreactive), for the morphometric analysis of the general population and nitrergic neurons and also for the immunoreactive varicosities to ChAT, VIP, CGRP or SP. Samples of the 3 intestinal segments were prepared and stained with hematoxylin and eosin for histological analysis of the basic morphology. Duodenum, the intestinal segment considered the most affected in the morphological analysis of the general population of neurons, was selected for the proteomic analysis...
Subject(s)
Animals , Male , Rats , Sodium Fluoride/administration & dosage , Sodium Fluoride/toxicity , Intestine, Small , Proteins/analysis , Enteric Nervous System , Fluorescent Antibody Technique , Intestine, Small/chemistry , Proteomics , Rats, Wistar , Reference ValuesABSTRACT
O trato gastrointestinal (TGI) é a principal rota de exposição ao fluoreto (F) e o seu mais importante sítio de absorção. Acredita-se que a toxicidade do F comprometa a fisiologia do intestino, devido à relevante sintomatologia gastrointestinal relatada em consequência da exposição excessiva ao F. A função intestinal é controlada por uma complexa rede neuronal interligada e incorporada à parede deste órgão, denominada Sistema Nervoso Entérico (SNE). Embora os efeitos tóxicos do F sobre o Sistema Nervoso Central sejam descritos na literatura, não há estudos relacionados à sua toxicidade sobre o SNE. Neste estudo realizado em ratos, foi avaliado o efeito da exposição aguda ou crônica ao F, sobre a população geral de neurônios entéricos e sobre as subpopulações que expressam os principais neurotransmissores entéricos: Acetilcolina (ACh), Óxido Nítrico (NO), Peptídeo Vasoativo Intestinal (VIP), Peptídeo Relacionado ao Gene da Calcitonina (CGRP) e Substância P (SP). Os animais foram divididos em 5 grupos: 3 destinados à exposição crônica (0 ppm, 10 ppm ou 50 ppm de F na água de beber) e 2 à exposição aguda (0 ou 25 mgF/Kg por gavagem gástrica). Foram coletados os 3 segmentos do intestino delgado (duodeno, jejuno e íleo) e processados para a detecção da HuC/D, ChAT, nNOS, VIP, CGRP e SP, através de técnicas de imunofluorescência, no plexo mioentérico. Foram obtidas imagens para a realização da análise quantitativa dos neurônios da população geral (HuC/D) e nitrérgicos (imunorreativos à nNOS); e morfométrica dos neurônios imunorreativos à HuC/D ou nNOS; e das varicosidades imunorreativas à ChAT, VIP, CGRP ou SP. Amostras dos 3 segmentos intestinais foram preparadas e coradas em Hematoxilina e Eosina para análise histológica da morfologia básica. O segmento intestinal considerado mais afetado na análise morfométrica da população geral de neurônios, o duodeno, foi selecionado para a realização da análise proteômica, com o objetivo de oferecer o seu perfil proteico...
The gastrointestinal tract (GIT) is the main route of fluoride (F) exposure, and the most important site of its absorption. It is believed that F toxicity compromises the intestine physiology, due to the relevant gastrointestinal symptomatology reported in consequence to excessive exposure. The intestinal function is controlled by a complex neuronal net, which is interconnected and embedded in the wall of this organ, named Enteric Nervous System (ENS). Although the toxic effects of F on the Central Nervous system are described in the literature, there are no studies related to its toxicity on the ENS. Therefore, in this study performed in rats, the effects of chronic and acute F exposure were evaluated, on the general population of enteric neurons and on the subpopulations that express the main enteric neurotransmitters: Acetylcholine (Ach), Nitric Oxide (NO), Vasoactive Intestinal Peptide (VIP), Calcitonin gene related peptide (CGRP), and Substance P (SP). The animals were divided into 5 groups: 3 designed to the chronic exposure (0 ppm, 10 ppm ou 50 ppm de F in the drinking water) and 2 to the acute exposure (0 ou 25 mgF/Kg - gastric gavage). Three intestinal segments were collected (duodenum, jejunum, and ileum) and processed for the immunofluorescence techniques to detect HuC/D, ChAT, nNOS, VIP, CGRP and SP, on the myenteric plexus. Images were obtained for the quantitative analysis of the general population of neurons (HuC/D immunoreactive) and the nitrergic neurons (nNOS immunoreactive), for the morphometric analysis of the general population and nitrergic neurons and also for the immunoreactive varicosities to ChAT, VIP, CGRP or SP. Samples of the 3 intestinal segments were prepared and stained with hematoxylin and eosin for histological analysis of the basic morphology. Duodenum, the intestinal segment considered the most affected in the morphological analysis of the general population of neurons, was selected for the proteomic analysis...
Subject(s)
Animals , Male , Rats , Sodium Fluoride/administration & dosage , Sodium Fluoride/toxicity , Intestine, Small , Proteins/analysis , Enteric Nervous System , Fluorescent Antibody Technique , Intestine, Small/chemistry , Proteomics , Rats, Wistar , Reference ValuesABSTRACT
Objective:To study the pharmacokinetics of propranolol in Wistar rats after acute exposure to high altitude. Methods:Fourteen male Wistar rats (200±20) g were selected. After administration of propranolol tablets (0.05 g/kg, i.g.), blood samples (3 mL) were collected at 0, 20, 40 min,1, 1.5, 2, 4, 6, 8, 12 and 24 h, respectively. The pharmacokinetic parameters were determined by LC-MS/MS and DAS 2.0 software. Results:The main pharmacokinetic area under concentration-time curve (AUC), mean retention time (MRT), half-life (t1/2) and peak plasma concentration (Cmax) of propranolol were increased by 442.61%, 47.45%, 73.13%and 352.97%, respectively, whereas Tmax and clearance (CL) were decreased by 80.87%and 68.94%, respectively. Conclusion:This study displays significant changes in the pharmacokinetics of propranolol under high altitude, which may provide evidence for clinical rational application of propranolol at high altitude.
ABSTRACT
Copper is an essential ion that forms part of the active sites of many proteins. At the same time, an excess of this metal produces free radicals that are toxic for cells and organisms. Fish have been used extensively to study the effects of metals, including copper, present in food or the environment. It has been shown that different metals induce different adaptive responses in adult fish. However, until now, scant information has been available about the responses that are induced by waterborne copper during early life stages of fish. Here, acute toxicity tests and LC50 curves have been generated for zebrafish larvae exposed to dissolved copper sulphate at different concentrations and for different treatment times. We determined that the larvae incorporate and accumulate copper present in the medium in a concentration-dependent manner, resulting in changes in gene expression. Using a transgenic fish line that expresses enhanced green fluorescent protein (EGFP) under the hsp70 promoter, we monitored tissue-specific stress responses to waterborne copper by following expression of the reporter. Furthermore, TUNEL assays revealed which tissues are more susceptible to cell death after exposure to copper. Our results establish a framework for the analysis of whole-organism management of excess external copper in developing aquatic animals.
Subject(s)
Animals , Cell Death/drug effects , Copper Sulfate/toxicity , Stress, Physiological/drug effects , Zebrafish , Animals, Genetically Modified , Embryo, Nonmammalian/drug effects , Green Fluorescent Proteins/metabolism , /metabolism , Immunohistochemistry , Larva/drug effects , Time Factors , Toxicity Tests, Acute , Water Pollutants, Chemical/toxicity , Zebrafish/embryologyABSTRACT
Objective To study the neurotoxic effects of acute exposure of methylmercury at low dose and to provide some experimental data for deeply exploring the early mechanism of neurotoxicity of methylmercury. Methods SD rats were administered with methylmercury chloride by intraperitoneal injection with different doses of 0.05, 0.50 and 5.00 mg/kg and different exposure times of 20 min, 1 h, 4 h, 24 h. Mercury, ACh and AChE contents in rat brains were measured. Results Mercury contents in rat brains significantly increased after 20 min-exposure at both 0.50 and 5.00 mg/kg doses. Significant increase occurred after 4 h exposure at dose of 0.05 mg/kg. ACh and AChE in rat brains significantly changed after 20 min at every dose, showing certain dose-response and time-response relations. Conclusion Changes of ACh and AChE in rat brain after administration of low dose(0.05 mg/kg) and short time(20 min) exposure suggested certain modulation of CNS had been initiated. With the increases of exposure dose and time, methylmercury might begin to accumulate in rat brain and induce the significant changes of ACh and AChE.