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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 establish the laboratory historical control values for biological indicators in SD rats with 28-day repeated dose oral toxicity tests. METHODS: The body mass, blood routine indexes, serum biochemical indexes, organ mass and organ coefficient of 10 batches of specific pathogen free SD rats in the control group and the control additional group were collected for 28-day repeated dose oral toxicity tests, and the historical control values was established. RESULTS: The body mass of both male and female SD rats increased with the increasing age(all P<0.01). The body mass of male rats was higher than that of female rats each week(all P<0.01). The body mass, blood routine and serum biochemical indexes, organ mass and organ coefficient of SD rats were affected by the age and gender of rats to varying degrees. The effects of age and gender on organ mass and organ coefficient were not consistent. The laboratory historical control values of body mass, blood routine indexes, serum biochemical indexes, organ mass and organ coefficient of SD rats were established according to the age measured in weeks and the gender of rats. CONCLUSION: The laboratory control values of biological indicators of SD rats should be established according to different weekly age and the gender of rats. Organ coefficient is more suitable as an observation index for toxicological safety evaluation compared with organ mass.
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OBJECTIVE: To study the metabolic characteristics of 5-bromo-2-fluorobenzonitrile in vitro and compare the differences between rats and human,and for the purpose of providing data for poison effect research and extrapolating poison effect of 5-bromo-2-fluorobenzonitrile from animals to human being. METHODS: Equilibrium dialysis method was used to analyze the protein binding ratio of 5-bromo-2-fluorobenzonitrile in the plasma of rats and humans in the groups of low dose,medium dose and high dose which were treated with mass concentration of 5-bromo-2-fluorobenzonitrile at 500,5 000 and 50 000 μg / L respectively. Metabolic incubation systems of SD rat microsomes and human liver microsomes were established in vitro. When the mass concentration of 5-bromo-2-fluorobenzonitrile in the systems was 800 μg / L,the concentration of liver microsome was 0. 5 g / L; after being incubated for 0,10,30,60 and 90 min with the involvement of the regeneration system of nicotinamide-adenine dinucleotide phosphate in the incubation systems,the metabolic reaction was stoped. The residual amounts of 5-bromo-2-fluorobenzonitrile were analyzed and metabolic half-life of 5-bromo-2-fluorobenzonitrile incubating with liver microsomes in vitro was figured out. RESULTS: Protein binding ratio of 5-bromo-2-fluorobenzonitrile in the groups of low dose,medium dose and high dose were( 83. 5 ± 0. 9) %,( 88. 8 ± 0. 3) % and( 88. 6 ± 0. 3) % in rats plasma,and( 85. 2 ± 0. 1) %,( 89. 0 ± 0. 1) % and( 91. 1 ± 0. 4) % in human plasma. Both in rat plasma and human plasma,the protein binding ratio of 5-bromo-2-fluorobenzonitrile in the groups of medium dose and high dose were significantly increased than that in the low-dose group( P < 0. 01). In human plasma,the protein binding ratio of 5-bromo-2-fluorobenzonitrile in the high-dose group significantly increased than that in the medium-dose group( P < 0. 01). In the groups of low dose and high dose,the protein binding ratio of 5-bromo-2-fluorobenzonitrile in human plasma significantly increased than that in rats plasma( P < 0. 01). Absolute differences in protein binding ratio of 5-bromo-2-fluorobenzonitrile between the rat plasma and the human plasma were no more than 2. 5% in the same dose groups. Metabolic half-life of 5-bromo-2-fluorobenzonitrile incubating with rats and human liver microsomes and control solution in vitro were respectively( 58. 6 ± 1. 6),( 59. 2 ± 1. 5) and( 65. 0 ± 6. 3) min,which shows no significant differences( P < 0. 05). CONCLUSION: The potein binding ratio and metabolism of 5-bromo-2-fluorobenzonitrile in liver microsomes in rat plasma is similar to those in human plasma. Both in the plasmas of rats and humans,5-bromo-2-fluorobenzonitrile has high protein binding ratio,and 5-bromo-2-fluorobenzonitrile is not metabolized in liver microsomes of either rats or humans.
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OBJECTIVE: To explore the effects of aquaporin 4( APQ4) in rat toxic brain edema induced by subacute 1,2-dichloroethane( 1,2-DCE) exposure. METHODS: Thirty-two specific pathogen free healthy adult female SD rats were randomly divided into control( 8 rats),low-dose( 12 rats) and high-dose( 12 rats) groups. The treatment groups were exposed to 1,2-DCE( low-dose: 600 mg / m3; high-dose: 1 800 mg/m3,nose-only) and the control group was exposed to fresh air by dynamic inhalation for 8 hours per day for consecutive 7 days. After exposure,histopathologic changes were examined in the cerebral cortex. Real-time polymerase chain reaction was used to detect the mRNA relative expression of matrix metalloproteinase 2( MMP2),Na-K-Cl cotransporter-1( NKCC1) and AQP4. The Western blotting was used to detect the expression of AQP4 protein in the cerebral cortex. RESULTS: The pathological results showed that the cerebral cortex tissues were loose around the peripheral vessels and the vessels tissue space appeared widen in low-dose exposure group. The pathological change was more serious in high-dose group than low-dose group,with obvious loosen vessels and vacuole. Compared with those of the control group and the low-dose group,the relative expression level of MMP2 mRNA in the high-dose group increased significantly[( 1. 07 ± 0. 41) vs( 1. 56 ± 0. 55),( 1. 21 ± 0. 59) vs( 1. 56 ± 0. 55),P <0. 05],while the the relative expression level of AQP4 mRNA in the high-dose group significantly decreased [( 1. 03 ±0. 25) vs( 0. 81 ± 0. 12),( 1. 00 ± 0. 20) vs( 0. 81 ± 0. 12),P < 0. 05]. The relative expression levels of NKCC1 mRNA in all groups showed no statistical difference [( 1. 03 ± 0. 31) vs( 1. 14 ± 0. 43) vs( 1. 36 ± 0. 50),P > 0. 05]. The relative expression level of AQP4 protein in the high-dose group was lower than that of the control group [( 0. 80 ± 0. 25) vs( 1. 19 ± 0. 42),P < 0. 05]. CONCLUSION: The brain edema induced by subacute inhalation of 1,2-DCE is of mixed types with vasogenic edema as its main symptom. Its pathogenesis is related to the changes of AQP4 expression.
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This study was aimed to investigate the distribution and implication of tap1 (transporter associated with antigen processing) and tap2 loci allelic and genotypic frequencies. The distribution of tap1 and tap2 loci allelic and genotypic frequencies in 339 random samples of healthy Chinese Hans was analyzed by TaqMan PCR. Several genetic information about power of discrimination, cumulative DP, polymorphism information content, expected heterozygosity and observed heterozygosity were calculated. The results indicated that 5 tap1 alleles (tap1*0101, 020101, 020102, 0301 and 0401) and 4 tap2 alleles (tap2*0101, 0102, 0103 and 0201) were detected in all samples. 8 tap1 genotypes were found which account for 53.3% of the theoretic genotype and 6 tap2 genotypes were found which account for 60% of the theoretic genotype. The genotyping results of tap1 and tap2 both conform to the Hardy-Weinberg expectations (p > 0.05). Tap1*0101 (79.79%) and tap2*0101 (82.74%) are the most common alleles in Chinese Hans. It is concluded that tap1*0101 and tap2*0101 are most common alleles in Chinese Hans, tap1 and tap2 loci carry some power of individual discrimination and polymorphism information content. These two locl can be used for the research in the fields of human genetics, linkage analysis of genetic disease genes, paternity test and individual identification and so on.