Subjects: Medicine, Pharmacy >> Preclinical Medicine submitted time 2018-06-15 Cooperative journals: 《南方医科大学学报》
Abstract： Objective To analyze the changes in endogenous small molecule metabolites after benzo[a]pyrene (B[a]P) exposure in rat cerebral cortex and explore the mechanism of B[a]P neurotoxicity. Methods Five- day- old SD rats were subjected to gavage administration of 2 mg/kg B[a]P for 7 consecutive weeks. After the exposure, the rats were assessed for spatial learning ability using Morris water maze test, ultrastructural changes of the cortical neurons under electron microscope, and metabolite profiles of the cortex using GC/MS. The differential metabolites between the exposed and control rats were identified with partial least squares discriminant analysis (PLS-DA) and the metabolic pathways related with the differential metabolites were analyzed using Cytoscape software. Results Compared with the control group, the rats exposed to B[a]P showed significantly increased escape latency (P<0.05) and decreased time spent in the target area (P<0.05). The exposed rats exhibited widened synaptic cleft, thickened endplate membrane and swollen cytoplasm compared with the control rats. Eighteen differential metabolites (VIP>1, P<0.05) in the cortex were identified between the two groups, and 9 pathways associated with B[a]P neurotoxicity were identified involving amino acid metabolism, tricarboxylic acid cycle and Vitamin B3 (niacin and nicotinamide) metabolism. Conclusion B[a]P can cause disturbance in normal metabolisms and its neurotoxicity is possibly related with disorders in amino acid metabolism, tricarboxylic acid cycle and vitamin metabolism.
Subjects: Medicine, Pharmacy >> Preclinical Medicine submitted time 2018-01-25 Cooperative journals: 《南方医科大学学报》
Abstract： Objective To observe the effect of chronic arsenic exposure on cerebral cortex and serum metabolics of mice and explore the mechanism of arsenic neurotoxicity. Methods Twelve 3-week-old male C57BL/6J mice were randomly assigned into exposure group and control group and exposed to sodium arsenite (50 mg/L) via drinking water and deionized water for 12 weeks, respectively. After the exposure, arsenic level in the cerebrum was determined by hydride generation-atomic fluorescence spectrometry. The metabolites in the cerebral cortex and serum were determined using gas chromatography-mass spectrometry (GC/MS) analysis. Principal component analysis (PCA) was used to analyze the difference of the metabolites between the exposure and the control groups. Online tools for analyzing metabolic pathways were used to identify the related metabolites pathways. ResultsArsenic content in the brain of exposure group was significantly higher than that in the control group(P<0.05).Themiceexposedtoarsenichadahigherlevelofcitricacid,phenylalanine,tyrosine,histidineandlysineinthe cerebral cortex (P<0.05). Serum levels of serine, glycine, proline, aspartate and glutamate were significantly higher while α-ketoglutaric acid level was significantly lower in the exposure group than in the control group (P<0.05). PCA analysis showed a significant difference in cerebral cortex and serum metabolites between the two groups. Conclusion Chronic arsenic exposure may affect the function of the central nervous system by interfering with amino acid metabolism and tricarboxylic acidcycle,whichmaybeoneofthemechanismsofarsenicneurotoxicity.
Subjects: Medicine, Pharmacy >> Preclinical Medicine submitted time 2018-01-25 Cooperative journals: 《南方医科大学学报》
Abstract： Objective To explore the effect of exposure to vehicle exhaust in pregnant mice on the reproductive function and DNA methylation in male offspring mice. Methods Twenty pregnant mice were randomized into control group and vehicle exhaust exposure group (n=10) and exposed to routine laboratory condition and to vehicle exhaust for 10 consecutive days (8 h per day) in a tunnel with a heavy traffic, where the concentrations of TSP, PM10, PM2.5, SO2 and NOX and the decibel of noise were measured. The offspring mice were raised till reaching maturity, and the epididymides of the male mice were collected to test the weight coefficients, DNA methylation level, and mRNA levels of Aldh7a1 and Rpe. Results The body weight and the weight coefficients of the epididymides and testes differed significantly between the exposure group and the control group (P> 0.05). The concentrations of TSP, PM2.5, PM10 and NOx and the decibel of noise were significantly higher in the traffic environment and the control environment (P<0.05). Reduced representation bisulphite sequencing (RRBS) and Gene ontology (GO) showed that 58 genes had significantly different methylation levels between the two groups, mostly relating to the process of spermatogenesis (P<0.05). Compared with the control group,Aldh7a1 and Rpe mRNAexpressions in the testes were down-regulated significantly in the exposure group (P<0.05). Conclusion Exposure of pregnant mice to vehicle exhaust causes damagesofthereproductivefunctioninthemaleoffspringmice.
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