Nitrite Exposure And DNA Methylation And Histone Acetylation In Mouse’s Cerebral Cortex

Nitrite is an inorganic salt which is widely found in human living enviroment,particularly soluble in water,unstable and decomposition,mainly sodium nitrite（NaNO₂）and potassium nitrite（KNO₃）commonly used.Nitrite always used in industry and construction industry,and widely used in all kinds of food industry as a preservative,is a necessary ingredient for all types of meat additives.It has also been used in the manufacture of dyes,nitroso compounds and rubber additives,medicines,which is closely related to people’s daily lives.However,epidemiology and numbers of animal experiments show that nitrite is a poison,excessive intake can cause harm to the human body.For example,preservatives used in meat products contribute to the generation of free radicals,resulting in increased lipid peroxidation,but free radicals play an important role in the toxic effects of different body organs.So its adverse effects can not be ignored,especially,human nitrite exposure has increased dramatically in recent years due to the extensive use of agricultural nitrogen fertilizers,anthropogenic disposal of inappropriate industrial wastes and nitrogen pollution in the atmosphere.Nitrate and nitrite levels in food and water have surprisingly exceeded the permissible limits in many areas.Excess nitrite into the human body,will lead to the emergence of hypoxia in the human body or intestinal symptoms of intestinal bruising,and even cause carcinogenic teratogenic hazards,especially pregnant women,anemia and glucose 6-phosphate dehydrogenase deficient individuals are more susceptible to nitrite toxicity.However the research on nitrite toxicity mechanism is rare.In this paper,we established chronic nitrite exposure models to compare the expression of inflammatory factors and the similarities and differences of DNA methylation and histone deacetylation protease expression between the control group and the nitrite exposure group by using immunohistochemical and Western-blot technique,to study the effects of inflammatory reaction and DNA methylation and histone deacetylation in mouse cortex.Objective:To observe the effect of chronic nitrite exposure on inflammatory injury of cerebral cortex in mice and investigate the role of DNA methylation and histone deacetylation in chronic nitrite exposure.Methods:6-8 week old healthy male C57BL/6J mice were randomly divided into control group（saline）,low dose of nitrite group（60 mg/kg）and high dose group（120 mg/kg）,nitrite exposure was collected to establish models,mouse cerebral cortex,using the free expression of immunohistochemical staining was used to detect cox2 and IL-1beta,Iba1,5-mC,DNMT1,DNMT3a,MBD2 and HDAC1,the expression of Western-blot protein in c-fos,IL-6,semi quantitative detection of DNMT1,DNMT3a,MBD2,HDAC1,so as to analyze the cerebral cortex inflammation and DNA methylation and histone acetylation level changes.Result:The expression of cox2,IL-1β,Iba1,c-fos and IL-6 were significantly more than those in the control group（P<0.01）after chronic nitrite exposure.On the other hand,the expression of 5-mC,DNMT1,DNMT3a and HDAC1 in treatment groups were significantly lower than those in control group（P<0.01）with dose dependency.Conclusion:Nitrite exposure can induce cell immune inflammatory damage in neocortex of mice,and DNA methylation and histone acetylation may be involved in regulation of immune inflammatory reaction after nitrite exposure.