Study On The Mechanism Of Neurotoxicity Induced By DINP In Mice Under Continuous Light

Diisononyl phthalate(DINP)is an important kind of phthalates(PAEs)and belongs to green plasticizer.It is widely used in the industrial production of various types of soft PVC products,rubber products and coatings,which greatly increases the risk of human exposure to DINP.The invention of the lamp makes artificial light sources widely used in various fields,and promotes the development of human technology,civilization,and productivity.Artificial light is self-evident for human beings.However,the most common health effects of continuous artificial light are the destruction of the circadian clock and the inhibition of melatonin production at night,affecting the sleep rhythm of the organism,and long-term exposure to artificial light at night(ALAN)may have a negative impact on human health.The environment in which people work and live is dominated by plasticizers and artificial light.It can be said that these two factors are everywhere.Extensive exposure to plastics and long-term exposure to artificial light greatly increase the exposure risk of DINP and ALAN.Therefore,it is necessary for us to jointly study these two factors to explore their effects and mechanisms on animal and human health.The mice were randomly divided into groups to simulate the real DINP and the real exposure environment that continued to stay up late at night.The light group was given 12 h natural light / 12 h continuous light(150 lux)each day.The aim was to investigate whether DINP combined with continuous light could further aggravate brain tissue damage in mice.After continuous exposure for 28 days,a water maze experiment was conducted for 7 days.After the exposure,brain tissue homogenate was used to measure reactive oxygen species(ROS),malondialdehyde(MDA),reduced glutathione(GSH),and 8-Hydroxy-2-deoxyguanosine,(8-OHdG),acetylcholine esterase(AChE).The pathological damage was observed by tissue section(HE,Nissl staining);the anti-apoptotic protein(Bcl-2)and pro-apoptotic protein(Bax)in mouse hippocampus were detected by immunohistochemistry.The experimental results show that with the increase of the DINP exposure dose,the mouse has found the target platform longer and longer,the swimming trajectory is gradually scattered without purpose,and the location memory ability of the target platform has also decreased,that is,the mouse's cognitive ability to learn Obviously affected;pathological sections showed that the hippocampal CA 3 area vertebral body cells showed different degrees of damage,the cells were loosely arranged and disordered,the cells were swollen and rounded or deformed,and the content of Nissl bodies in the cells decreased significantly.The content of ROS,MDA,8-OHd G,AChE and Bax in brain tissue also gradually increased,and the content of GSH and Bcl-2 gradually decreased,the difference was statistically significant(P<0.05,P<0.01).Compared with the light 200 mg / kg DINP group,the 200 mg / kg DINP group had differences in 8-OHdG and AChE(P<0.05);and after the addition of antioxidant vitamin E(VitE),the contents of 8-OHdG and AChE decreased significantly(P<0.01),GSH increased significantly(P<0.05),alleviating the oxidative damage caused.In summary,with the increase of DINP concentration exposure,the body's antioxidant function is reduced,and the oxidative stress pathway is stimulated,which in turn causes Bcl-2,AChE to rise and Bax to fall.Continuous light can aggravate the mice caused by DINP Oxidative damage leads to the death of nerve cells in the body and impairs the learning ability and memory of mice.Under the combined exposure of ALAN and DINP,the effect on learning ability and memory of mice is more severe than that of the group exposed to DINP alone.Oxidative stress may be an important molecular mechanism affecting its process,and the antioxidant VitE has two effects The oxidative damage caused by factors has a certain antagonistic effect.