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Background As an environmental pollutant, 1-bromopropane (1-BP) is ubiquitous in the living environment. However, its health effects on the general population are still unclear. Objective To assess the associations between urinary 1-BP metabolite and blood routine indices in a Chinese community population. Methods A total of 3512 community residents aged 18-80 years from the baseline of the Wuhan-Zhuhai cohort were included in our study. The demographic characteristics, disease history, and lifestyles of the participants were collected through questionnaires. Height, weight, blood pressure, and other anthropometrics were collected through physical examination. Blood routine indicators were tested using an automated hematology analyzer. Urinary 1-BP metabolite N-Acetyl-S-(n-propyl)-L-cysteine (BPMA) was measured by ultra-high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. Generalized linear models and logistic regression models were used to assess the associations of urinary BPMA with blood routine indices and the risks of abnormal blood routine indices, respectively. Besides, stratified analysis and effect modification analysis were further conducted to investigate the effects of individual characteristics and lifestyles on the associations of urinary BPMA with blood routine indices. All models were adjusted for gender, age, and other potential confounders. Results The mean age of the study population (30.1% male) was (52.78±12.77) years. The median (P25, P75) level of urinary BPMA adjusted for urinary creatinine was 0.90 (0.50, 1.73) mg·mol−1. In the analysis with target indicator as continuous variable, each 1-unit increase in natural logarithm-transformed urinary BMPA level was associated with a 0.078×109 L−1, 0.031×109 L−1, 0.307%, 3.518 g·L−1, and 2.469×109 L−1 decrease in white blood cell, lymphocyte, lymphocyte percentage, mean corpuscular hemoglobin concentration, and platelet levels, respectively (all Ps<0.05); and with a 0.440%, 1.140 fL, 0.014 fL, and 0.020 increase in hematocrit, mean corpuscular volume, and natural logarithm-transformed levels of mean platelet volume and mean platelet volume/platelet, respectively (all Ps<0.05). The categorical analysis across quartiles of BPMA level showed that BPMA was inversely associated with lymphocyte percentage, mean corpuscular hemoglobin concentration, and platelet levels in a dose-dependent manner (all Ptrend<0.05), and positively related to hematocrit, mean corpuscular volume, mean platelet volume, and mean platelet volume/platelet levels in a dose-dependent manner (all Ptrend<0.05). Body mass index, smoking, and drinking modified the associations of urinary BPMA level with red blood cell, mean corpuscular hemoglobin concentration lymphocyte percentage, and hemoglobin (all Ps<0.05). In addition, urinary BPMA was associated with an increased risk of abnormal increase in mean corpuscular volume (OR=1.316, 95%CI: 1.171-1.478) and red blood cell volume distribution width (OR=1.255, 95%CI: 1.030-1.528), and abnormal decrease in mean corpuscular hemoglobin concentration (OR=1.200, 95%CI: 1.035-1.392). Conclusion Exposure to 1-BP of the general population is associated with decreased white blood cells and platelets, as well as abnormal change of blood cell morphology or function.
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Objective:To observe the role of neuroinflammation in cognitive dysfunction induced by 1-bromopropane (1-BP) in rats.Methods:Male Wistar rats were randomly divided into control group, 1-BP group, pyrrolidine dithiocarbamate(PDTC)+ 1-BP group and PDTC group, with 15 rats in each group. Rats in 1-BP group and PDTC+ 1-BP group were given 800 mg / kg 1-BP by gavage, and rats in control group and PDTC group were given equal volume corn oil once a day for 12 days; rats in PDTC group and PDTC+ 1-BP group were intraperitoneally injected with 100 mg / kg PDTC 30 minutes after gavage, while rats in control group and 1-BP group were injected with equal volume of normal saline once a day for 12 days.From the 7th to 12th day of the experiment, ten rats in each group were randomly selected and subjected to Morris water maze test for detect the cognitive function. In the positioning navigation test, the learning ability of rats was evaluated by the escape latency and total swimming distance respectively. In the space exploration experiment, the memory ability of experimental animals was evaluated by the number of times crossing the target platform. After the experiment, ten rats were sacrificed, the cerebral prefrontal cortex was harvested. The cytosolic and nuclear NF-κB expression and phosphorylation were detected by Western blot, the mRNA levels of TNF-α and IL-1β were detected by qRT-PCR. After cardiac perfusion fixation, the brains of 5 rats were taken to make frozen sections for immunohistochemical staining and Nissl staining. SPSS 20.0 software was used for statistical analysis, repetitive measurement deviation analysis was used for the analysis of the swimming distance and the escape latency in positioning navigation test, One-way ANOVA was used for the analysis of the number of times crossed the target platform in spatial probe test and other data. Tukey's test was used for Post hoc comparison.Results:The results of Morris water maze showed that there was significant interaction between group and training time in the total swimming distance of rats in the four groups ( F=3.762, P<0.05). Simple effect analysis showed that the total swimming distance of 1-BP group in 1-4 days were longer than those of control group (all P<0.05), while the total swimming distance of PDTC+ 1-BP group in 1-4 days were shorter than those of 1-BP group (all P<0.05). There was significant interaction between group and training time in the escape latency among the four groups ( F=6.541, P<0.01). The escape latencies of 1-BP group in 1-4 days were longer than those of control group (all P<0.05), while the escape latencies of PDTC+ 1-BP group in 1-4 days were shorter than those of 1-BP group (all P<0.05). The results of space exploration experiment showed that there was significant difference in the number of crossing the platform among the four groups ( F=75.333, P<0.01). The number of crossing the platform (1.08±0.29) in 1-BP group was lower than that in the control (3.35±0.05) ( P<0.01). The number of crossing the platform (1.95±0.26) in PDTC+ 1-BP group was higher than that in 1-BP group ( P<0.01). It had significant difference both in the cytoplasm and in the nucleus of the NF-κB protein level in prefrontal cortex among rats of the four groups ( F=20.865, 23.877, both P<0.01). The levels of NF-κB in cytoplasm and nucleus of rats in 1-BP group were both higher than those in control group (cytoplasm: (177.3±32.1)%, (100.0±8.4)%, P<0.01; nucleus: ( 173.2±27.1)%, (100.0±8.4)%, P<0.01). While the levels of NF-κB in cytoplasm and nucleus of 1-BP+ PDTC group were both lower than those of 1-BP group (cytoplasm: (148.7±22.0)%, (177.3±32.1)%, P<0.01; nucleus: (149.7±18.8)%, (173.2±27.1)%, P<0.01). The results of qRT-PCR showed that there were significant differences in the mRNA levels of TNF-α and IL-1β in the prefrontal cortex among the four groups ( F=17.464, 17.382, both P<0.01). The levels of TNF-α and IL-1β mRNA in 1-BP group were higher than those in control group (both P<0.05), and the levels of TNF-α and IL-1β mRNA in PDTC+ 1-BP group were both lower than those in 1-BP group (both P<0.05). The results of immunohistochemistry showed that compared with the control group, the number of microglia and astrocytes in the 1-BP group increased (microglia: (158.30±9.68), (110.20±16.30), P<0.05; astrocytes: (122.76±4.35), (80.24±6.96), P<0.05), and the morphology was also activated, with light staining and reduced number of Nissl bodies in neurons.The number of microglia and astrocytes in PDTC + 1-BP group was lower than that in 1-BP group (microglia: (131.70±14.67), (158.30±9.68), P<0.05; astrocytes: (101.54±4.55), (122.76±4.35), P<0.05), and the Nissl body staining of neurons was significantly deepened. Conclusion:NF-κB signaling pathway might be the key mechanism of 1-BP neurotoxicity. PDTC intervention could significantly improve the neuroinflammatory response and behavioral disorders of experimental animals intoxicated with 1-BP.
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OBJECTIVE: To compare the applicability of two risk assessment methods for occupational health risk assessment in enterprises with 1-bromopropane(1-BP) production and utilization. METHODS: Three enterprises with 1-BP production and utilization were selected as the research subjects by a typical sampling method. The exposure concentration of time-weighted average of 1-BP-exposed in worker was detected. The non-carcinogenic health risk of 1-BP was assessed using the USA Environmental Protection Agency(EPA) inhalation risk(EPA assessment model) and the Ministry of Manpower of Singapore(MOM assessment model), and the results were compared. RESULTS: When the EPA method was used for the assessment, the risk assessment results of the four posts in the manufacturing enterprises were all negligible. In the enterprises that use 1-BP, the posts of cleaning machine B and clamping were of medium risk and the other four posts were of low risk based on the occupational exposure limit(OEL) in China used as the reference exposure concentration(RfC). When the 24-hour minimal risk level of USA Agency for Toxic Substances and Disease Registry was used as the RfC, the posts of cleaning machine B and clamping were of extreme high risk; the posts in cleaning machine A and checking were of high risk; the post in the cleaning machine D was of medium risk and the post of cleaning machine C was of low risk. When the MOM assessment model was used for evaluation, the four posts were of low risk in the 1-BP production enterprises. In the enterprises that use 1-BP, the posts of cleaning machine B and clamping were of high risk; the posts of cleaning machine A, cleaning machine D and checking were of medium risk; and the post of cleaning machine C was of low risk. CONCLUSION: When the OEL value is used for risk assessment, the MOM assessment method is more suitable than the EPA assessment method to assess occupational health risks of 1-BP.
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OBJECTIVE: To observe the neurotoxicity and hematotoxicity of maternal exposure to 1-bromopropane(1-BP) on the offspring rats by the breast-feeding route. Method A total of eight specific pathogen free female rats and their 64 male newborn rats were divided into the control group and the exposure group, with four lactation female rats and their 32 male newborn rats in each group. The female rats in exposure group were intragastrically administered with 700.00 mg/kg body mass of 1-BP during lactation, and the control group was given equal volume of corn oil for 21 days, once a day. The body mass of female rats and their offspring rats were measured during the exposure period. After exposure, the Morris water maze and the open field tests were performed in male offspring. The blood samples of offspring were collected for blood routine and blood biochemical indexes detection. The histopathological examination was performed in the hippocampus in the male offspring. RESULTS: A litter of eight pups in the exposure group began to die one day after the mother rat was exposed to 1-BP, and all rats died on the ninth day after exposure. There was no significant difference in the body mass of female rats between the exposure group and the control group(P>0.05). The body mass of offspring rats in the exposure group was lower than that in the control group at the same time point from the first day to the 21 st day of the female rats exposed to 1-BP(all P<0.05). In the orientation navigation experiment, the escape latency time on the first, the second day and the total distance on the first day in the offspring of the exposure group were significantly prolonged than those in the control group at the same time points(all P<0.05). The number of times of crossing the platform of offspring rats in the exposure group was less than that in the control group in the spatial exploration test(P<0.01). In the open field test, there was not statistical significance of the activity, rest time ratio, total distance, the distance ratio and time ratio in the central region in the offspring between the two groups(all P>0.05). The counts of white blood cells, neutrophils, lymphocytes, and average red blood cell width, platelet ratio and average platelet volume of the offspring of the exposure group decreased(all P<0.05), the serum levels of globulin, total protein, triacylglycerol and total bilirubin decreased(all P<0.05), and the albumin/globulin ratio and serum glucose level increased(all P<0.05), when compared with that of the control group. Histopathological examination results showed that the nerve fibers were loose in the hippocampal dentate gyrus area, and there were necrotic neurons and loss of nerve fibers in the CA1 area of the offspring rats. CONCLUSION: Maternal exposure to 1-BP during lactation can induce neurotoxicity and hematotoxicity to offspring rats. The neurotoxicity mainly caused damage to the central nerve system, which affected the learning and memory function of the offspring rats. The reason may be related to the damage caused by 1-BP on the hippocampal function.
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OBJECTIVE: To observe the sub-acute toxicity of 1-bromopropane(1-BP) oral exposure for 28 days in SD rats. METHODS: Specific pathogen free adult female SD rats were randomly assigned to the control and exposed group, 8 rats in each group. The 1-BP was suspended in corn oil and administered by gavages in a dose of 800 mg/kg body weight to rats in the exposed group, once a day, 5 days per week for 4 weeks. The rats in the control group were given equal volume of corn oil. After the last exposure, blood and urine of rats were collected for 1-BP level detection and hematological examination. Brain, heart, lung, liver, kidney and spleen of rats were collected for gross pathological examination and histopathological examination. RESULTS: The rats of exposed group showed unstable standing, weakness of hind limbs, limping and lying down from the 3 rd week of exposure. From the 1 st to 4 th week of exposure, mean body weight of rats in the exposed group were significantly lower than those of the control group(P<0.05). In the exposed group, the level of 1-BP in urine was higher than that in blood(P<0.05), and that there was positive correlation between them(Spearman correlation coefficient=0.954, P<0.01). In the control group, 1-BP was not detected. The absolute weights of brain and lung tissue in the exposure group decreased(P<0.05), meanwhile the organ coefficients of heart, liver, spleen and kidney were significantly increased compared with the control group(P<0.05). The number of red blood cells, hemoglobin concentration, hematocrit, the mean hemoglobin concentration, the total serum cholesterol and triglycerides were decreased(P<0.05). No pathological change related to 1-BP exposure was observed in the main organs of the rats in the exposed group. CONCLUSION: The sub-acute oral toxicity of 1-BP is mainly neurotoxicity and hematotoxicity. The 1-BP level in urine may reflect its exposure.
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Objective@#To investigate the changes in mass spectrometry of proteins in patients with 1-bromopropane (1-BP) poisoning after treatment and their biological functions.@*Methods@#From May 2016 to December 2017, 3 male patients aged 31-47 years with 1-BP poisoning in Bao'an District of Shenzhen, China were enrolled in this study. The whole blood sample (2 ml) was collected before and after treatment. Label-free mass spectrometry-based proteomics was used for protein identification and quantification. The differentially expressed proteins after treatment were analyzed. Bioinformatics tools were used to analyze the functions of the identified proteins and the biological processes they were involved in.@*Results@#Proteomic analysis showed that there were 47 proteins that were differentially expressed more than 2-fold (P<0.05) after treatment in the patients with 1-BP poisoning; of them, 27 were up-regulated and 20 were down-regulated in the serum of treated patients. The identified proteins were mainly involved in proteolysis, protein modification, immune response, complement activation, lipoprotein metabolism, signal transduction, and coagulation.@*Conclusion@#The differentially expressed proteins after treatment can help with the diagnosis, treatment, and prognosis monitoring of 1-BP poisoning and provide potential therapeutic and prognostic markers for 1-BP poisoning treatment.
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Occupational exposure to 1-bromopropane (1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors (NMDARs) and neuroinflammation are involved in the cognitive impairments in neurodegenerative diseases. In this study we aimed to investigate whether the noncompetitive NMDAR antagonist MK801 protects against 1-BP-induced cognitive dysfunction. Male Wistar rats were administered with MK801 (0.1 mg/kg) prior to 1-BP intoxication (800 mg/kg). Their cognitive performance was evaluated by the Morris water maze test. The brains of rats were dissected for biochemical, neuropathological, and immunological analyses. We found that the spatial learning and memory were significantly impaired in the 1-BP group, and this was associated with neurodegeneration in both the hippocampus (especially CA1 and CA3) and cortex. Besides, the protein levels of phosphorylated NMDARs were increased after 1-BP exposure. MK801 ameliorated the 1-BP-induced cognitive impairments and degeneration of neurons in the hippocampus and cortex. Mechanistically, MK801 abrogated the 1-BP-induced disruption of excitatory and inhibitory amino-acid balance and NMDAR abnormalities. Subsequently, MK801 inhibited the microglial activation and release of pro-inflammatory cytokines in 1-BP-treated rats. Our findings, for the first time, revealed that MK801 protected against 1-BP-induced cognitive dysfunction by ameliorating NMDAR function and blocking microglial activation, which might provide a potential target for the treatment of 1-BP poisoning.
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Animals , Male , Brain , Metabolism , Pathology , Cognitive Dysfunction , Drug Therapy , Metabolism , Pathology , Disease Models, Animal , Dizocilpine Maleate , Pharmacology , Excitatory Amino Acid Antagonists , Pharmacology , Hydrocarbons, Brominated , Inflammasomes , Metabolism , Maze Learning , Physiology , Microglia , Metabolism , Pathology , NLR Family, Pyrin Domain-Containing 3 Protein , Metabolism , Neurons , Metabolism , Pathology , Nootropic Agents , Pharmacology , Random Allocation , Rats, Wistar , Receptors, N-Methyl-D-Aspartate , Metabolism , Spatial Memory , Physiology , Specific Pathogen-Free OrganismsABSTRACT
Objective@#To investigate the occupational health survey of 1-brominepropane (1-BP) enterprises and understand the impact of 1-BP on the health of occupational exposure population.@*Methods@#The occupational health data of 15 1-BP workers were collected from 3 time nodes in 0 months, June and December, and the effects of occupational exposure to 1-BP on health were analyzed.@*Results@#In the workplace with pure 1-BP, the mean air concentration in the workplace was 26.8 mg/m3, and the personal contact level was 29.7 to 63.4 mg/m3. The occupational health monitoring data showed that white blood cell count (WBC) , red blood cell count (RBC) , aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were compared in 0 months, June, and 12 months, the difference was statistically significant (P<0.05) .@*Conclusion@#During the 12 months observation period, the occupational exposure to 1-BP caused the number of peripheral blood erythrocyte and leukocyte count and the level of alanine transaminase in the workers, but it did not exceed the normal reference range.
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Objective@#To analysis the occupational exposure to 1-bromopropane on the worker’s nerve conduc-tion velocity.@*Methods@#To PubMed, Wanfang, VIP, Chinese Journal Full-text Database (CNKI) and other databases as a data source, searched and screened database to October 2017 on occupational exposure to 1-bromopropane workers on the role of nerve conduction in the paper. According to inclusion and exclusion criteria, we screened literatures, extracted data and evaluated the quality of the included studies, using RevMan5.3 software to test the heterogeneity of the results and us-ing the corresponding mathematical model for data combination analysis.@*Results@#A total of 5 articles were included in the literature. The results showed that the tibial nerve MCV of workers in the 1-bromopropane exposure group was slower than that in the control group (SMD=-0.47,95%CI=-0.70~-0.24) , the difference was statistically significant (Z=4.06, P<0.01). The tibial nerve DL of the exposure group was more prolonged than that of the control group (SMD=0.35,95%CI=0.00~0.69) , with a statistically significant difference (Z=1.99, P=0.05). The sural nerve SCV of the exposure group was slower than that of the control group (SMD=-0.47, 95%CI=-0.78~-0.15), with a statistically significant difference (Z=2.88,P<0.01).@*Conclusion@#Occupational exposure to 1-bromopropane may have an effect on the worker's nerve conduction ve-locity.It’s necessary to do broader and deeper neurotoxicity studies about 1-bromopropane.
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OBJECTIVE: To explore the effects of sub-acute inhalation of 1-bromopropane( 1-BP) on the ultrastructure of cerebral cortex,hippocampus,cerebellum,and brainstem in male rats. METHODS: Specific pathogen free healthy male Wistar rats were randomly divided into control group and exposure group with 6 rats in each group. The rats of exposure group received 1-BP vapor at a concentration of 5 000 mg/m3. The rats in the control group were given fresh air in a dynamic inhalation chamber system for 4 weeks(6 hours/day,5 days/week). After the end of the exposure,the cerebral cortex,hippocampus,cerebellum and brainstem of rats were collected and the ultrastructural changes were observed under transmission electron microscope( TEM). RESULTS: After 3 weeks of exposure to 1-BP,the rats in the exposure group began to have unresponsiveness and decreased muscle strength in hind limbs. The body weight of exposure group was lower than that of control group from the 1 st to the 4 th week( P < 0. 05). TEM results showed destroyed structure of the myelin sheath in the region of cerebral cortex, hippocampus, cerebellum and brainstem, and irregular nucleus, vacuolar degeneration,increased lysosome of endoplasmic reticulum,mitochondrion swelling of neuron cells,karyopyknosis of astrocytes and vacuolation in the neurite of astrocytes located in the blood brain barrier( BBB). CONCLUSION: 1-BP sub-acute inhalation exposure could damage the myelin,neuron,astrocyte and BBB in male rats. The demyelination of nerve fiber and decreased permeability of BBB was particularly noticeable.
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OBJECTIVE: To investigate the therapeutic effect of electroacupuncture on peripheral nerve damage induced by 1-bromopropane( 1-BP) exposure.METHODS: A total of 25 specific pathogen free healthy adult male Wistar rats were randomly divided into blank control group( n = 5),model control group( n = 10),and electroacupuncture treatment( EA) group( n = 10).Rats in the blank control group were not exposed to 1-BP and treated with electroacupuncture.The rats in model control group and EA group were placed in a dynamic inhalation exposure cabinet with 1-BP at concentration of 5 000 mg/m~3.The rats were continuously exposed to 1-BP 8 hours per day,5 days a week,for 4 weeks.At the 3 rd day after the end of the exposure,the EA group was treated with electroacupuncture on“Zu sanli”and“Huantiao”points for 4 courses.Each course included 20 minutes each time,once per day for 7 consecutive days.The body weight,the motor nerve conduction velocity( MCV) and sense nerve conduction velocity( SCV) of sciatic nerves on both posterior limbs of the rats were measured.RESULTS: During the course of 1-BP exposure,the rats in the EA and model control group showed reduction of eating,drinking and activities,limited autonomic activities and their hind limbs dragged.The MCV and SCV of posterior limb sciatic nerve of rats in the model control group were slower than that of the control group at the 4 th,6th and 8th week and the 0 week of the same group( P < 0.05).The MCV and SCV of posterior limb sciatic nerve of rats in the EA group improved with the increase of treatment time( P < 0.05),and those at the 6th and 8th weeks of the experiment( corresponding to the 2nd and 4th week after treatment) were faster than that of the model control group at the same time( P < 0.05).The SCV of the posterior limb sciatic nerve in the EA group recovered to normal level 4 weeks after treatment compared with the blank control group( P < 0.05).CONCLUSION: Electroacupuncture treatment can promote the recovery of peripheral nerve damage in rats with 1-BP poisoning.
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Objective@#To investigate the changes in protein expression in patients with 1-bromopropane (1-BP) poisoning using high-throughput proteomic technique and to screen out protein markers.@*Methods@#Serum samples were collected from 3 patients with 1-BP poisoning and 15 controls. The label-free proteomic tech-nique was used for the quantitation and identification of proteins expressed in these samples, and the results were compared between the patients with 1-BP poisoning and the control population. The bioinformatics tools were used to analyze the function of differentially expressed proteins.@*Results@#Compared with the control popula-tion, the patients with 1-BP poisoning had >2-fold upregulation of 38 proteins and >2-fold downregulation of 68 proteins. The differentially expressed proteins were mainly involved in immune response, signal transduction, and stress response.@*Conclusion@#The proteins screened out may be potential protein markers for 1-BP poison-ing, which provides reliable and precise methods and thoughts for the diagnosis of 1-BP poisoning.
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Objective@#To study the electrophysiological changes and pathological characteristics of peripheral nerve in rats exposed to 1-bromopropane through chronic inhalation.@*Methods@#40 male SD rats were randomed divided into 4 groups, and exposed to 1-bromopropane vapor at concentrations of 1 000 mg/m3, 2 000 mg/m3, 4 000 mg/m3 and fresh air respectively, 6 hours per day, 5 days per week for 12 weeks. The changes of nerve conduction velocity (NCV) , electromyography (EMG) and pathology were observed.@*Results@#After 4 weeks of exposure, the body weights of high dose group are lower than that of the control group. Compared with the control group, the high and medium dose group have a decline in MCV and CMAPs, while SCV and SNAPs descend in the high dose group (P<0.05) . The EMG examination showed that there are denervation changes in high dose group. Sciatic nerve biopsy observed by electron microscope showed that axonal degeneration and demyelination coexist in the rats exposed to high concentration.@*Conclusion@#Chronic inhalation of 1-bromopropane at the concentration of 4 000 mg/m3 can cause peripheral nerve injury, which is characterized by axonal degeneration and demyelination. Axonal degeneration is the main pathological change.
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Objective@#To observe the effect of nerve growth factor (NGF) and Mecobalamin on chronic peripheral neuropathy in rats induced by 1-bromopropane.@*Methods@#36 male SD rats were exposed to 1-bromopropane vapor at concentrations of 4 000 mg/m3, 6 hours per day, 5 days per week for 12 weeks. The rats were randomed divided into 4 groups, and treated by Mecobalamin for 300 μg/kg qd, NGF for 40 μg/kg qd, Mecobalamin+NGF with the dose as mentioned above, respecively. The control group were fed in normal condition. The changes of Sciatic nerve conduction velocity (NCV) , electromyography (EMG) and pathology were observed 30 days later.@*Results@#The nerve conduction velocity were decreased in all the rats. Compared with the control group, the motor nerve conduction velocity (MCV) was improved in group Mecobalamin and group Mecobalamin+NGF, The difference was statistically significant, as the sensory nerve conduction velocity (SCV) was improved only in group Mecobalamin+NGF. Sciatic nerve biopsy observed by electron microscope showed that myelinated nerve fibers were obvious swelling, lamellar separation, partial myelin vacuolization, and axonal degeneration. After treatment with exogenous nerve growth factor, the number and severity of damaged nerve fibers were restored.@*Conclusion@#Exogenous nerve growth factor contributes to the recovery of peripheral nerve damage induced by 1-bromopropane.
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OBJECTIVE To observe the neurotoxicity of 1-bromopropane(BP) and investigate the protective effects of edaravone(Edv) against BP-induced deficits of spatial learning and memory ability in rats by its anti-inflammatory mechanism. METHODS Adult male Wistar rats were ig given BP 800 mg·kg-1 to develop the model, followed by Edv 1, 3 and 5 mg·kg-1 ip treatment respectively 4 h later for consecutive 12 d. From the 7th day (d 7), all rats were subjected to the five-day place navigation in Morris water maze (MWM) to measure the escape latency and the total swimming distance. On d 6 of MWM, spatial probe test was performed and the crossing times of rats were recorded to evaluate the spatial memory ability. At the end of the behavioral experiment, four rats in each group were randomly selected and the frozen section of the whole brain was sliced for thionin staining and immunohisto?chemistry. The other eight sacrifced rat brains from each group were harvested for the determination of the tumor necrosis factor-α (TNF-α) and nitric oxide (NO) by ELISA and nitrate reductase method, respectively. RESULTS The results of MWM test showed that compared with control rats the escape latencies of rats in BP group were increased by 60.8%, 81.9%,124.0% and 323.3%, respectively, during the d 2-d 5 of MWM, and the total swimming distance increased by 47.0%, 66.4%, 106.0% and 277.6%, respectirely. All the differences between BP group and control group were significant (P<0.05, P<0.01). In the spatial probe trial, the crossing times of rats in BP group were significantly decreased, compared with the control rats (P<0.01). Morphologically, thionin staining and immunohistochemistry revealed significant microglia activation and neuron loss in the rat forebrains, accompanied by a 147.6% and 18.7% increase in NO and TNF-α levels in rats treated with BP respectively compared with control values (P<0.05, P<0.01). After co-treatment at different dosages of Edv with BP, the escape latencies of rats in BP+Edv 5 mg·kg-1 group were decreased by 38.4%and 44.3%(P<0.01), and the total swimming distance decreased 34.5%and 43.3%(P<0.05, P<0.01), respectively, compared with the BP treated rats on the d 4 and d 5 of MWM test. The microglia activation and neuron damage in the brain of rats induced by BP treatment were significantly alleviated in BP+Edv groups. In addition, the contents of NO and TNF-α were decreased in BP+Edv 1, 3 and 5 mg · kg-1 groups, with a decrease of 53.8%, 55.4% and 59.8% in NO, and 12.2%, 15.8% and 22.2% in TNF-α(P<0.05, P<0.01), respectively. CONCLUSION Edv could effectively protect against central neurotoxicity induced by BP via anti-neuro?inflammation.
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OBJECTIVE: To establish a detection method for 1-bromopropane in human urine by headspace gas chromatography-mass spectrometry( GC-MS). METHODS: A 4. 00 m L portion of the urine sample was placed in a 15. 00 m L headspace vial and 20. 00 μL of 1-bromobutane internal standard solution( 204. 200 mg / L mass concentration) was added.The bottle cap was immediately sealed. The sample was heated to 80 ℃ with an equilibrium time of 20 minutes in the headspace device. The vapor in the headspace vial was separated by GSBP-FFAP( 30. 00 m × 0. 25 mm × 0. 25 μm)capillary chromatography column and the ion was used to carry out quantitative determination of 1-bromopropane in human urine. RESULTS: The good linearity range of 1-bromopropan mass concentration was 0. 025-1. 012 mg / L, and the correlation coefficient was 0. 999 8. The detection limit was 7. 5 μg / L( urine sample volume,4. 00 m L) and the limit of quantitation was 25. 0 μg / L( urine sample volume,4. 00 m L). The relative standard deviation( RSD) of within-run precision was 2. 61%-4. 08%,and the RSD of between-run precision was 2. 79%-6. 25%. The average recovery rate was99. 34%-105. 94%. CONCLUSION: The method of determining 1-bromopropane in human urine by headspace GC-MS has the features of high sensitivity,good linear relationship,low interference,good precision and easy operation,which is suitable for detecting 1-bromopropane mass concentration in human urine.
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OBJECTIVE: To determine the effects of 1-bromopropane( 1-BP) subacute inhalation on the expression of neuron specific enolase( NSE) and myelin basic protein( MBP) in plasma and brain tissue in male rats. METHODS: Specific pathogen free adult male Wistar rats were randomly divided into 4 groups with 12 rats in each group: the control group,the low-,medium- and high-dose groups with 1-BP exposure levels at 0,1 250,2 500 and 5 000 mg / m3,respectively. The rats were given continuous dynamic inhalation of 1-BP for 6 hours per day,5 days per week,for continuous 4 weeks. The rats were sacrificed at the end of exposure,9 rats from each group were randomly chosen and the blood from abdominal aorta was collected and the plasma was isolated. The plasma levels of NSE and MBP were measured by enzyme-linked immunosorbent assay. The whole brain,pallium,cerebellum and brainstem were isolated for detection of organ coefficient.The rest of 3 rats in each group were processed for histopathologic examination and the expressions of NSE and MBP were evaluated by immunohistochemistry. RESULTS: The organ coefficients of whole brain,pallium,cerebellum and brainstem in the high-dose group were higher than those in the control group [( 0. 754 ± 0. 056) % vs( 0. 663 ± 0. 035) %,( 0. 382 ±0. 037) % vs( 0. 339 ± 0. 021) %,( 0. 115 ± 0. 008) % vs( 0. 098 ± 0. 006) % and( 0. 213 ± 0. 018) % vs( 0. 183 ±0. 014) %,respectively,P < 0. 01]. The plasma NSE levels in the 3 exposure groups were lower than those of control group [( 7. 92 ± 0. 53) vs( 24. 73 ± 11. 44),( 9. 12 ± 2. 17) vs( 24. 73 ± 11. 44) and( 11. 10 ± 2. 84) vs( 24. 73 ±11. 44) mg / L,respectively,P < 0. 01]. The plasma MBP levels in all groups showed no statistical difference [( 2. 52 ±0. 70) vs( 2. 50 ± 0. 72) vs( 2. 47 ± 0. 66) vs( 2. 44 ± 0. 81) mg / L,P > 0. 05]. Histopathological examination showed that a few necrotic nerve cells were observed in hippocampus of rats in high-dose group. The expressions of NSE and MBP in brain tissue of rats in control,low- and medium-dose groups showed no significant difference. The down-regulated expression of NSE and MBP were only observed in cells of hippocampus of rats in the high-dose group. CONCLUSION: The1-BP induced neural toxicity was reflected in the function of central nervous system rather than in the structural morphology. The plasma NSE might be one of the effect biomarkers for monitoring 1-BP exposure.
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OBJECTIVE: To study the potential effects of subacute 1-bromopropane( 1-BP) inhalation on the expression of synapse specific biomarkers synaptophysin( SYP),glutamate receptor 2( GluR2) and N-methyl-D-aspartate receptor 2B( NR2B) in the hippocampus of male rats. METHODS: Forty-eight specific pathogen free adult male Wistar rats were randomly divided into control group,low-,medium-,and high-dose groups according to body weight. Each group consisted of 12 rats. By dynamic inhalation intoxication method,the control group was exposed to fresh air,the dose groups were given 1 250,2 500 and 5 000 mg / m3 of 1-BP respectively,6 hours per day,5 days per week for continuous 4 weeks. After the exposure,the rats were executed and the whole brains were separated into cerebrum( included hippocampus),brainstem and cerebellum. Real time quantitative polymerase chain reaction and Western blot were used for detection of SYP,GluR2 and NR2 B mRNA and protein expression in hippocampus. RESULTS: Slow response and muscle strength descended in hind limbs were found in high-dose group in the 3rd week. Body weights of rats in high-dose group were lower than those of control group from the 1st to the 4th week( P < 0. 01). Weights of whole brain,cerebrum and brainstem in high-dose group were lower than those of control group( P < 0. 05). Rats in high-does group were found neuron necrosis in hippocampus cornu ammonis 3 and dentate gyrus region. No significant difference was found in SYP,GluR2 and NR2 B mRNA relative expression in all groups( P > 0. 05). No significant difference was found in SYP protein relative expression in different groups( P > 0. 05). The GluR2 protein relative expression in high-dose group was lower than that of control group( P < 0. 05). The NR2 B protein relative expression was higher than that of control group( P < 0. 05). CONCLUSION: The GluR2 and NR2 B protein expression in hippocampus can be potential biomarkers for 1-BP central neurotoxicity,but its physiological meaning needs further elucidation.
ABSTRACT
OBJECTIVE: To analyze the clinical features of occupational chronic toxic peripheral neuropathy caused by1-bromopropan( 1-BP). METHODS: Clinical data of 4 patients who suffered from occupational chronic toxic peripheral neuropathy caused by 1-BP were collected for retrospective analysis. RESULTS: The 4 male patients were ultrasonic cleaning operation workers in a hardware vacuum coating enterprise. They were exposed to high levels of 1-BP for 9-11 months. The main clinical manifestations were varying degrees of sensory disorder and dyskinesia. The main symptoms were progressive increase of numbness and fatigue in the lower extremities. These symptoms might be accompanied by unsteady gait.Physical examination showed muscle strength weakness in the double lower limbs. The hypalgesia,pselaphesia,topesthesia and pallesthesia decreased in the double lower limbs or 4 limbs. The bilateral achilles tendon reflex mainly showed reduced or disappeared. One case had sensory ataxia. Electroneuromyography examination showed different levels of peripheral nerve damage among the cases. The motor nerve conduction velocity and sensory nerve conduction velocity reduced commonly. The axon and myelin sheath damage were visible. On the basis of GBZ / T 247-2013 Diagnosis of Occupational Chronic Toxic Peripheral Neuropathy Caused by Chemicals,these cases were diagnosed as occupational chronic toxic peripheral neuropathy caused by 1-BP. CONCLUSION: Long-term exposure to high level 1-BP can lead to chronic poisoning with peripheral nervous system damage. The diagnosis can be made based on the 1-BP exposure history,clinical features and the neurogenic damage found in electroneuromyography examination.