| Objective:1,2-Dichloroethane(1,2-DCE),that is colorless,tasteless oily liquid,a synthetic organic chemical that is utilized as a general organic solvent,particularly as the thinner of adhesives and the manufacture of vinyl chloride.1,2-DCE can be evaporated quickly into the air of workplace,and the workers may inhale the high concentrations of its vapor via the respiratory route.Cerebral edema is deemed to be the main pathological processes involved in the toxic encephalopathy.Abundant experimental studies have suggested that the metabolites generated in CYP2E1 mediated metabolism of 1,2-DCE are 2-chloroethanol(2-CE)and chloroacetaldehyde,and finally formed chloroacetic acid.Furthermore,more Reactive oxygen species(ROS)could be generated from CYP2E1mediated metabolism due to its intense NADPH oxidase activity.ROS is a class of substances formed by oxygen,which contain oxygen in the molecular composition and it is more active than oxygen itself.ROS also would cause oxidative damage in liver and brain.Based on the theory mentioned above,oxidative damage in brain might cause cerebral edema.This study was designed to explore the protective effect of vitamin C on toxic cerebral edema caused by 1,2-DCE before poisoning,which could provide experimental reference data for revealing the toxic mechanisms of cerebral edema caused by 1,2-DCE.Methods:Mice were randomly divided into six groups,including blank control group,vitamin C control group,1,2-DCE poisoned group,and low,middle and high dose vitamin C intervention groups.Mice in the control and 1,2-DCE poisoned group were treated by gavage with physiological saline,however mice in the vitamin C intervention groups were given with 25,100 and 400 mg/kg vitamin C dissolved in physiological saline,respectively.Thereafter,mice in 1,2-DCE poisoned group and vitamin C intervention groups were exposed to 1.2 g/m~3 1,2-DCE,3.5 h per day,for 3 days.Mice in the control group were kept in the chamber without exposure to 1,2-DCE.One day after the last exposure,the mice from each group were deeply anesthetized with ether and sacrificed by decapitation.Their brains were dissected immediately for detections of brain water content,levels of reduced glutathione(GSH),malondialdehyde(MDA),activity of superoxide dismutase(SOD),and both protein and mRNA levels of CYP2E1,Nrf2 and HO-1,and pathological section of brain tissues were observed.Mean and standard deviations were calculated for each experimental group,and analyzed by SPSS for Windows,version 20.0.Significance testing was by one-way analysis of variance with multiple comparisons by the Student-Newman-Keuls test.Results:1.The main symptoms of nervous system diseases in 1,2-DCE poisoned group accounted for limb tremor,the limbs could not be fully extended,accompanied by elbow bend,which was a phenomenon of the crossed front legs or limbs called claw-holding.2.Compared to the control group,MDA levels and water contents in the brain of 1,2-DCE poisoned group significantly increased,however,GSH level and SOD activity in the brain decreased significantly(P<0.05).On the other hand,compared to the 1,2-DCE poisoned group,MDA levels and water contents decreased significantly,and GSH level and SOD activity increased significantly in the brain of high dose vitamin C intervention group(P<0.05).3.Compared to the control group,both protein and mRNA levels of CYP2E1,Nrf2 and HO-1 in 1,2-DCE poisoned group significantly increased(P<0.05).4.Compared to the 1,2-DCE poisoned group,both protein and mRNA levels of CYP2E1 and HO-1,and protein levels of Nrf2in high dose vitamin C intervention group decreased significantly(P<0.05).Conclusions:1.1,2-DCE poisoning can cause increased brain water content in mice and typical pathological changes of cerebral edema.2.1,2-DCE poisoning could cause oxidative damage in the brain and significantly upregulate the expressions of CYP2E1,Nrf2 and HO-1.3.Vitamin C could improve the oxidative damage induced by1,2-DCE,and play a protective effect for toxic cerebral edema. |
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