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Joint toxic effect of formaldehyde and DEHP on learning and memory of mice |
LU Lin-jie, CAI Jie, AN Jie-ran, DU Jun-ting, DING Shu-mao |
Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Central China Normal University, Wuhan 430079, China |
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Abstract To explore the combined toxic effect of formaldehyde and DEHP on learning and memory of mice and the mechanism, Kunming mice were randomly divided into 14groups:(1) the control group; (2) FA (formaldehyde) group:0.5mg/m3, 1mg/m3, 3mg/m3; (3) DEHP group:5mg/kg, 50mg/kg, 500mg/kg; (4) the joint exposure:0.5mg/m3 +5mg/kg, 1mg/m3 +50mg/kg, 3mg/m3 +500mg/kg; (5) VE group:saline+VE (100mg/kg), FA3.0mg/m3 + VE, DEHP500mg/kg + VE, FA3.0mg/m3 + DEHP500mg/kg + VE. The mice of FA and joint exposure groups were exposed to gaseous formaldehyde for 8h everyday (continuous exposure for 5days, interval for two days), and the mice of DEHP and joint exposure groups were gavaged with DEHP solution. Besides, blocking groups were also gavaged VE solution (100mg/kg) everyday. Their behaviors of learning and memory were tested by Morris water maze experiment. Then the change of biological indicators including oxidative damage, ROS, MDA, TNF-α, IL-β, and 5-HT, etc, was detected in the cerebral tissue. Results showed that Morris water maze test in space training and learning indicated that escape latency significantly extended in 3.0mg/m3 of formaldehyde and 500mg/kg of DEHP treatment group, 1.0mg/m3 +50mg/kg and 3.0mg/m3 +500mg/kg of the combined treatment groups (P<0.05). Compared with single exposure groups, escape latency significantly extended in the moderate and high dose of combined treatment groups (P<0.05). In space exploration experiments, the proportion of time of the target quadrant in 1.0mg/m3 and 3.0mg/m3 of formaldehyde treatment groups, the 500mg/kg of DEHP treatment group, and 1.0mg/m3 +50mg/kg, 3.0mg/m3 +500mg/kg of the combined treatment groups were less than the control group (P<0.05). The proportion of time of the target quadrant in combined treatment groups were significantly decreased compared with single exposure (P<0.05). Compared with control group,the contents of ROS and MDA in 1.0mg/m3 and 3.0mg/m3 of formaldehyde, 50mg/kg and 500mg/kg of DEHP groups and all the joint exposure groups were increased, while the contents of GSH decreased in 3.0mg/m3 of formaldehyde, 500mg/kg of DEHP groups and all the joint exposure groups decreased. Compared with formaldehyde or DEHP exposure groups, the contents of GSH in joint exposure groups were significantly decreased (P<0.01). The expression level of inflammatory factor TNF-α and IL-β were also significantly increased, and Caspase-3 was activated. The content of 5-HT in 3.0mg/m3 +500mg/kg of joint exposure group was significantly decreased (P<0.01). 0.5mg/m3 of formaldehyde had little effect on mice and their behaviors of learning and memory didn't obviously change. This study shows that 1.0mg/m3 and 3.0mg/m3 of formaldehyde and 500mg/kg of DEHP treatment group and 1.0mg/m3 +50mg/kg, 3.0mg/m3 +500mg/kg of the combined treatment groups could cause Kunming mice oxidative damage and inflammation. The joint exposure of formaldehyde and DEHP has synergistic effect. And VE could protect brain tissue by reducing Oxidative stress, inflammation, the level of Caspase-3, and increasing the content of 5-HT.
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Received: 13 May 2017
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