Study On The Effect Of Diisononyl Phthalate On Learning And Memory Ability Of Kunming Mice

Phthalate esters(PAEs)are synthetic organic compounds.Due to their good physical and chemical properties,PAEs are often used as plasticizers for polyvinyl chloride(PVC)materials to increase the extensibility,flexibility and plasticity of plastic products.The new environmentally friendly plasticizer di-isodecyl phthalate(DIDP)is favored for its low toxicity.A number of potential toxicity studies on DIDP have been carried out worldwide,but there are few studies on its neurotoxicity,and the related molecular mechanisms are still unclear,especially the impact on brain function has not been reported.This study selected DIDP to explore its effects on the nervous system.In order to study the effect of DIDP on the learning and memory ability of mice,Kunming mice were continuously intragastrically administered for 9 days,during which Morris water maze experiments were performed simultaneously.On the tenth day,the brain tissue of mice was removed for detection of the content of ROS,GSH,MDA,8-OH-dG,TNF-α and IL-1β.H&E and Nissl staining were performed on hippocampal slices of mice to observe pathological changes.Brain cell damage was observed by immunohistochemistry to measure the expression level of Caspase-3 and GFAP.The protective mechanism of resveratrol(Res)on brain tissue after DIDP exposure was studied by measuring the expression of transcription factor Nrf2,antioxidant NQO-1 and HO-1.The results showed that the learning and memory ability of the mice in the 15,150 mg/kg/day DIDP group decreased significantly,and their brain tissue produced oxidative stress and promoted the release of inflammatory factors,activated the apoptotic factor Caspase-3,and caused damage to hippocampal neurons.Res,as a protective agent,can reduce the levels of oxidative stress,inflammation and apoptosis in brain tissue,reduce pathological damage,and improve the learning and memory impairment in mice.In summary,the decline in learning and memory ability of mice induced by DIDP may be related to the oxidative damage of hippocampus in brain tissue,and Res promotes the antioxidant factors NQO-1 and HO-1 by activating Nrf2 pathway,effectively attenuating the oxidative stress level of brain tissue,thereby reducing the learning and memory impairment in mice.