ABSTRACT
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.
ABSTRACT
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.