The Combined Toxicity And Elementary Mechanism Of Lead And Dibutyl Phthalate In Mice And Zebrafish Embryos

Environmental pollution problem frequently occurred with the development of economy. Dibutyl phthalate(DBP) is used as plasticizers and additives in plastics,pesticides, cosmetics and other products. Lead(Pb) is a kind of the heavy metal pollutants and ubiquitously diffused in the environment. DBP and Pb have been found to be widely distributed in atmosphere, aquatic, soil and food.People exposured to DBP and Pb at the same time would run a potential health risk. Numerous studies have been demonstrated on the toxicity of individual DBP and Pb, but few were on the joint effects and mechanism. Thus, in the present study, the various toxic indicators relevant parameters of subject were analyzed to determine the combined toxicity and elementary mechanism of DBP and Pb by weanling mice and zebrafish embryos in vivo. This study is concerned with basic research on joint exposure, which is of great significance to human health. The main results are listed as follows:The first part: the effect of learning and memory and elementary mechanism of Lead and Dibutyl phthalate in weanling miceIn this aspect of the study, Pb(50 mg/L by drinking water), DBP(10, 250 mg/kg body weight by oral gavage) were administered individually and mixtures to 3-week old mice for 8 weeks. The effect of learning and memory and elementary mechanism of Pb and DBP in weanling mice were analyzed by behavior, enzymology and western blotting.1, In Morris water maze, compared with the control group, all exposure groups showed an increase in the escape latency and decrease in the average number of mice crossing site the platform(p<0.05), which demonstrated that the combination of Pb and DBP impaired memory and spatial learning. Factorial variance analysis showed that the two caused synergistic toxic effects(p<0.05).2, The content of Pb in mice showed that Pb in various tissues of mice have a certain degree of accumulation, especially in the brain. It is demonstrated that the brain is the target organ of Pb. Pb can accumulate in the brain tissue, which could affect the learning and memory in mice.3, In enzymology and western blotting. The mechanism of learning and memory damage induced by Pb and DBP in mice might be summarized as follows:(1)Exposureto Pb and DBP induced NOS over-expressing in brain of mice, causing the content of NO significantly increase. Moreover, the activity of SOD was decreased, the levels of MDA was increase. These induced lipid peroxidation in brain,causing brain cell damage.(2)Exposure to Pb and DBP induced the activity of AChE significantly increased, cholinergic neurons activation radioactivation and out-of-balance in ACh metabolic, causing nerve injury of mice.(3) Pb and DBP induced a significant increase in the expression of apoptosis-related protein(Bax/Bcl-2 ratio and caspase-3), causing apoptosis of hippocampal cells in mice.The second part: The combined toxicity and elementary mechanism of Lead and Dibutyl phthalate in zebrafish embryosIn this aspect of the study, Pb(0,0.01,1 mg/L), DBP(0,0.005,0.5 mg/L) were administered individually and mixtures to zebrafish embryos for 120 h. Quantitative real-time PCR was used to assess the neurotoxicology, apoptosis, development,immune and antioxidant related expressions. The combined toxicity and elementary mechanism of Pb and DBP in zebrafish embryos was studied.1, Exposure to Pb and DBP induced the expression of NRIA, NR2 A, NRAD and c-fos gene increase, bcl-2 gene decrease. It indicated that Pb and DBP could influence neurotoxicity and apoptosis related expressions, neural development and apoptosis in zebrafish embryos, causing toxicity in zebrafish embryos. it hasn’t interaction.2, Exposure to Pb and DBP induced the expression of hsp70 decrease, the expression of cyp1 a increased. It indicated that Pb and DBP could influence the development of related expressions, causing zebrafish embryos developmental toxicity. it hasn’t interaction.3, Exposure to Pb and DBP induced the expression of IL-1β and C3 B gene increased, and Lyz gene decreased. It indicated that Pb and DBP could influence the expressions of related immune genes, causing zebrafish embryos immunotoxicity.4, Exposure to Pb and DBP induced the expression of Cu/Zn-SOD、Mn-SOD andGPx gene increased. It indicated that Pb and DBP could influence the expression of the related antioxidant, causing imbalance of antioxidant system in zebrafish embryos.it hasn’t interaction.