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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 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 explore the mechanism of bone marrow mesenchymal stem cells( BMSCs) in alleviating pulmonary alveolitis in mice exposed to silica dust. METHODS: Five specific pathogen free healthy male C57 BL /6 mice were used to isolate BMSCs using bone marrow adherent method. The poly-potent differentiation ability of BMSCs were identified by 3 differentiation-inducing experiments. Forty-five mice of similar background were randomly divided into 3groups: control group,silica group and BMSCs transplantation group. The mice of the control group were given 20. 0 μL of0. 90% sodium chloride solution by one time intratracheal injection. The mice of silica group and BMSCs transplantation group were first received 20. 0 μL( 250 g / L mass concentration) of silica dust suspension by one time intratracheal injection; followed by 500. 0 μL of 0. 90% sodium chloride solution or 500. 0 μL of BMSCs suspension( cell density 1 ×109/ L) by tail vein infusion 6 hours later. Mice were euthanized on the 3rd day of the experiment. Lung functional coefficient and pathologic changes in the lung were examined. The level of cytokines in bronchoalveolar lavage fluid( BALF) was detected by enzyme linked immunosorbent assay. Wright-Giemsa staining was used for staining cells in BALF for counting. Flow cytometry( FCM) was used to measure the percentage of macrophages of BALF in the mice. RESULTS: BMSCs were successfully induced to differentiate into osteogenic,adipogenic and chondrogenic cells and developed into osteoblast,adipogenic cells and chondroblast. On the 3rd day of the experiment,the mice in silica group showed histopathological changes similar to pulmonary alveolitis; while there was no obvious inflammatory change observed in the BMSCs transplantation group,and the structure of lung tissue appeared normal. The lung coefficient of the silica group was higher than that of the control group( P < 0. 05); the lung coefficient of BMSCs transplantation group was lower than that of the silica group( P < 0. 05),but it showed no significant difference when compared to the control group( P > 0. 05). The interleukin( IL)-1β,IL-6 and chemokine ligand 3 levels in BALF in the silica group were higher than those of the control group( P < 0. 05),and the above 3 indices in the BMSCs transplantation group regaining the level of the control group( P > 0. 05) were lower than those of the silica group( P < 0. 05). The level of tumor necrosis factor-α in BALF in silica group and BMSCs transplantation group were higher than that of the control group( P < 0. 05),but there was no significant difference between silica group and BMSCs transplantation group( P > 0. 05). The level of IL-10 in BALF showed no significant difference in these 3 groups( P > 0. 05). Wright-Giemsa staining results showed that the number of total cells and macrophages in BALF in the silica group was higher than that of the control group( P < 0. 05),and the above cell number of BMSCs transplantation was lower than that of silica group( P < 0. 05),but it showed no significant difference when compared to the control group( P > 0. 05). The FCM result showed that the percentage of macrophages was in accordance with that of the Wright-Giemsa staining. CONCLUSION: The BMSCs can alleviate pulmonary alveolitis in the mice exposed to silica dust by inhibiting the amounts and activity of alveolar macrophages and down-regulating the expression of IL-1β and IL-6 in BALF.
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OBJECTIVE: To investigate the effects of 1,2-dichloroethane( 1,2-DCE) on myelin basic protein( MBP),neuron specific enolase( NSE) and S100 protein in the plasma of SD rats. METHODS: Forty-eight specific pathogen free adult SD rats were randomly divided into control group,low-dose group and high-dose group,with 8 females and 8 males in each group. Rats were given 1,2-DCE orally at the dose of 0,27 and 79 mg / kg body weight every other day( every Wednesday,Monday and Friday) for 4 weeks. After 1,2-DCE administration,8 survived rats( half male and female) were randomly selected in each group. The plasma levels of MBP,NSE and S100 protein were measured using enzyme-linked immunosorbent assay. The blood and urinary samples were collected to assess the concentration of 1,2-DCE and its main metabolites( 2-chlorideacetic acid, 2-chlorideacetaldehyde and 2-chlorideethanol) by gas chromatography. The pathological changes of cerebrum and cerebellum were observed through optical microscope,and the expression of MBP was detected by immunohistochemistry. RESULTS: Rats in high-dose group showed abnormal behavior from the third day of1,2-DCE exposure and 6 rats( 2 females,4 males) died from 1,2-DCE intoxication. Rats in low-dose group and control group appeared normal and no death was observed. MBP level in the plasma of high-dose group was higher than that in the control group( P < 0. 05),but the levels of NSE and S100 protein in each group did not show significant statisticaldifference( P > 0. 05). 1,2-DCE and 2-chloroethanol in the urine were detected in the high-dose group,and were below detection limit in the other two groups. 2-Chloroacetic acid level in high dose-group was significantly higher than that in the low-dose group( P < 0. 05),and was below detection limit in the control group. 2-Chloroacetaldehyde in the urine of each group was below detection limit. 1,2-DCE and its 3 kinds of metabolites were not detected in the plasma of all rats. There was no obvious structural damage,bleeding,edema or necrosis found in the cortex and white matter of cerebrum and cerebellum. The expression of MBP in the choroid plexus epithelial cells were significantly enhanced in the lateral ventricle and the fourth ventricle of rats in the high-dose group,and slight enhanced in rats in the low-dose group. CONCLUSION: MBP may play a role in the toxic effect of 1,2-DCE.