Study On The Effect Of Combined Exposure To Formaldehyde And DEHP On The Learning And Memory Abilities Of Mice And Its Mechanism

Formaldchyde(FA)and phthalate(2-ethyl)hexyl ester(DEIIP)are important chemicals in the global economy,and their production and consumption are increasing year by year.In recent years,with the safety study caused by environmental pollutants,people found formaldehyde and DEHP can not only cause damage to the ecological environment,more harm to our human health.So it caused the extensive concern of scientists.The formaldehyde and DEHP research mainly concentrated in each of the respiratory system,the influence of the reproductive system,endocrine system.Not only the lack of both single exposure on the nervous system of exploring the mechanism of toxicity,moreover,formaldehyde and DEHP are the main component of indoor air pollutants,and the human body are often exposed to the comprehensive environmental pollutants.So there is a need for the study on the joint exposure of FA and DEHP inducing neurotoxicity.In order to give further evaluation whether the toxicity of FA and DEHP is collaborative and study the possible mechanism of damage,this research tested the learning and memory ability of mice,brain histopathological observation and brain tissue damage by conducting the single and joint experiment of formaldehyde and DEHP.At the same time,antioxidant vitamin E(VE)was used as the protection group to further explore the possible protective effect of VE on oxidative damage of brain tissue.In this study,to explore the combined toxic effect of formaldehyde and DEHP on learning and memory of mice and the mechanism,Kunming mice were randomly divided into 14groups:(1)the control group;(2)FA(formaldehyde)group:0.5mg/m3,1mg/m3,3mg/m3;(3)DEHP group:5mg/kg,50mg/kg,500mg/kg;(4)the joint exposure:0.5mg/m3+5mg/kg,1mg/m3+50mg/kg,3mg/m3+500mg/kg;(5)VE group:saline+VE(100mg/kg),FA3.0mg/m3+ VE,DEHP500mg/kg + VE,FA3.0mg/m3+ DEHP500mg/kg+ VE.The mice of FA and joint exposure groups were exposed to gaseous formaldehyde for 8h everyday(continuous exposure for 5days,interval for two days),and the mice of DEHP and joint exposure groups were gavaged with DEHP solution.Besides,blocking groups were also gavaged VE solution(100mg/kg)everyday.Then the change of biological indicators including oxidative damage,ROS,MDA,TNF-?,IL-?,and 5-HT,etc,was detected in the cerebral tissue.Results showed that the escape latency of 3.0mg/m3 of formaldehyde and 500mg/kg of DEHP treatment groups were observably extended,so did 1.0mg/m3+50mg/kg and 3.0mg/m3+500mg/kg of the combined treatment groups(P<0.05).Compared with the mere exposure groups,the escape latency observably extended in moderate and high dose of joint treatment groups(P<0.05).In space exploration experiments,the time in target quadrant of 1.0mg/m3 and 3.0mg/m3 of formaldehyde treatment groups,the 500mg/kg of DEHP treatment group,and 1.0mg/m3+50mg/kg,3.0mg/m3+500mg/kg of the joint treatment groups were less than the control group(P<0.05).The time in target quadrant of combined treatment groups were observably decreased,compared with the mere exposure groups(P<0.05).Compared with control group,the contents of ROS and MDA in 1.Omg/m3 and 3.0mg/m3 of formaldehyde,50mg/kg and 500mg/kg of DEHP groups and all the joint exposure groups were increased,while the contents of GSH decreased in 3.0mg/m3 of formaldehyde,500mg/kg of DEHP groups and all the joint exposure groups decreased.Compared with formaldehyde or DEHP exposure groups,the contents of GSH in joint exposure groups were observably decreased(P<0.01).The expression level of inflammatory factor TNF-a and IL-? were also observably increased,and Caspase-3 was activated.The content of 5-HT in 3.0mg/m3+500mg/kg of joint exposure group was observably decreased(P<0.01).0.5mg/m3 of formaldehyde had little effect on mice and their behaviors of learning and memory didn't obviously change.This study shows that 1.Omg/m3 and 3.0mg/m3 of formaldehyde and 500mg/kg of DEHP treatment group and 1.0mg/m3+50mg/kg,3.0mg/m3+500mg/kg of the joint treatment groups could cause Kunming mice oxidative damage and inflammation.The joint exposure of formaldehyde and DEHP has synergistic effect.And VE could protect brain tissue by reducing Oxidative stress,inflammation,the level of Caspase-3,and increasing the content of 5-HT.