The Study Of Biomarkers And Effects On Sciatic Nerve In Rats Exposed To1-Bromopropane

ObjectiveTo expore toxic effects of1-bromopropane(1-BP) on the rat sciatic nerves and to search for the early indicators via establishing the subacute1-BP intoxication model of rats. The urine of the rats were determined to find the exposure biomarkers.MethodsIn the subacute toxicity study,48male Wistar rats were randomly divided into4groups,12rats per group. With the dynamic inhalation method, rats were exposed to1-bromopropane vapor at concentrations of0,1250,2500and5000mg/m3daily for8hours,5days per week for4weeks. After administration, the animals were housed individually in metabolic cages and the urine samples were collected. The body weights were measured every four days. On experimental day29, each animal was weighed, anesthetized with mebumalnatrium and electrophysiological tests were carried on sciatic nerves. Motor and sensory nerve conduction velocity, as well as distal latency and amplitude was measured.9rats were sacrificed with collecting blood for the routine blood examination and biochemistry tests by puncturing into abdominal aorta. Then the other3rats in each group were dissected for pathological examination. Determining the3-bromopropionic acid with GC and total bromine in the urine with ICP-MS every four days.Results1. The1-BP-exposed rats exhibited symptoms and signs of smaller quantity of eating, less activity, and pilose rarefaction. The body weight of the exposed group were significantly lower than that of control group. The rats of the high dose group were found muscle weakness at three weeeks after administration.2. Nerve conduction velocity examination showed that the exposured group has a significant decrease in both of the right and left motor nerve conduction velocity (MNCV) of sciatic nerves (P<0.01) and increase of distal motor latency(DML)(P<0.05or P<0.01). However, only the bilateral sensory nerve conduction velocity (SNCV) declined significantly (P<0.05or P<0.01) and the distal sensory latency (DSL) were elongated (P<0.05) in the high exposure group. The difference of SNCV and DSL between the low and middle dose group and the controlled group were not significant (P>0.05). By the ANOVA analysis, the amplitude of the poisoned group and the control group had no statistical difference (P>0.05).3. The routine blood examination showed that in the high dose group the red blood cell(RBC) and the hemoglobin(Hb) of the rats were significantly decreased (P<0.05) compared with those of the control. However, the MCV, the MCH and the MPV were all higher than that of the controlled group (P<0.05). Results of serum biochemical detection:As compared to control group, the level of AST and ALT are markedly increased(P<0.01). The amount of TP and IgG are increased notedly with the evaluation of1-BP concentration, whlie a reverse trend were observed in CK, CP, IgM and calcium ion.4. Compared with the control group, the myelin of rat sciatic nerves were found with bubble-like degeneration, offset axon and increased gap were be also seen under the light microscope in rats treated with1-BP in the concentration of5000mg/m3.5. The results indicated that no3-BPA was detected in any of the samples.The content of urinary bromide in three treatment groups, which was positively related to the concentration of1-BP, were higher than that of the controls (P<0.01). With the extending time of exposure to1-BP, the concentration of bromide in urine was increased. Conlusion1. In this study, we found the nerve conduction velocity of the sciatic nerves were slower and the distal latency were longer, and the motor nerve was more sensitive to1-BP exposure than nerve sensory nerve. The pathological changes of the myelin and the axonal in rat sciatic nerves were observed. The motor nerve conduction velocity of the sciatic nerve may serve as a predictor of the early damage to the nervous system induced by1-BP.2. The changes of the MCV, MCH, MPV, AST and ALT are sensitive when the rats exposed to1-BP and there are a good dose-response relationship between them. The amount of the TP, IgG, CK, CP, IgM and calcium ion in serum are also notedly changed in a dose-dependent fashion with1-BP concentration. All the mentioned may be as the biomarkers to assessment the risk of1-BP exposure.3. These results suggest that the amount of bromide in the urine could be used as effective biomarker of1-BP exposure.