The Study Of Effects And Mechanism Of Titanium Dioxide Nanoparticles On Plasma Glucose In Mice

With the development of the material technology,nanomaterials have been a daily commodity in close with human.Among these materials,titanium dioxide nanoparticle(TiO2 NP),as a food additive,is one of the most intake nanomaterials of common human.As showed in literatures,TiO2 NPs can dagame the digestive system,the urinary system,the nervous system,and the reproductive system.However,so far as I know,there is still no study focus on the effects of TiO2 NPs on the endocrine system.Diabetes is one of the endocrine diseases that seriously threaten the human health.In China,the prevalence of diabetes mellitus in over 30 years old people can reach 11.6%.Now China has become the world's largest country of diabetes.There are many risk factors for diabetes mellitus.The changes of lifestyle and food structure are important factors for diabetes mellitus.Whether various food additives,especially nano-food additives,are the risk factor of diabetes mellitus cannot be ignored.Therefore,eight-week-old adult CD-1 male mice were treated with 50 mg/kg body weight P25,which is a commonly used TiO2 NP in food,by oral administration.As the controls,mice were also treated with TiO2 fine particle(FP)as the non-nanolevel of titanium dioxide,and another TiO2 NP.Results showed that,after orally administered P25,the nanoparticles can be absorbed into blood and accumulated in liver,spleen,kidney,heart,and pancreas of mice,and induced damages to these organs.Meanwhile,NP can also be absorbed and accumulated in each organs and induced damages in organs,but FP cannot be absorbed and accumulated in mice.P25 was also treated to three-week-old young CD-1 male mice,and results showed that P25 can also be absorbed and accumulated in each organ and induced damages in organs.However,damages of young mice can be repaired during these mice grow up.P25 was treated to CD-1 pregnant mice,results showed that P25 directly reduce the number of offspring in the pregnant mice.Then mice plasma glucose levels were measured in the process that they were treated with all kinds of TiO2 by oral administration.Results showed that,P25 and NP significantly increased plasma glucose in adult mice,but FP cannot.The TiO2 nanoparticles did not affect insulin secretion in adult mice,and this phenomenon was valued to the mechanism study.This study also showed that P25 increased plasma glucose in young mice,and the increasing of plasma glucose in young mice was earlier than that of adult mice.TiO2 nanoparticles also did not affect insulin secretion in young mice.However,though TiO2-induced damages of organs can be repaired in young mice,TiO2 NPs-increased plasma glucose can not return to the normal levels in young mice.In addition,oral administration of TiO2 nanoparticles in pregnant mice can not affect plasma glucose in offspring of these pregnant mice.When these offspring mice grow up to three-week-old,we treated these offspring mice with TiO2 nanoparticles,and found that oral administration of TiO2 nanoparticles in their mother also did not affect the ability that TiO2 nanoparticles increased plasma glucose of them.The full transcriptome sequencing of the liver of mice exposed to TiO2 NPs was carried out by RNA-sequencing(RNA-seq)technology,and results showed that TiO2 NPs induced 335 differential gene expressions,and there were 204 up-regulated genes and 131 down-regulated genes.These genes significantly enrich in 53 gene ontology(GO)terms and 9 KEGG pathways.These GO terms and KEGG pathways showed that,as xenobiotics,TiO2 NPs activated an enobiotic biodegradation response and increased expression of CYP450 s in mouse livers,which induced reactive oxygen species(ROS)generation and endoplasmic reticulum stress,The ROS generation and endoplasmic reticulum stress activated NF-?B and MAPK pathways and induced an inflammation response,which phosphorylated the serine of IRS-1 and thus induced insulin resistance in mice.Also we found that endoplasmic reticulum stress contributed to the ROS generation of TiO2 nanoparticles-treated mie.This study expands the knowledge of the toxicological effects of nanomaterials,and provides a basis for the endocrine toxicological study of nanomaterials.