Joint toxic effect of formaldehyde and DEHP on learning and memory of mice

LU Lin-jie1 CAI Jie1 AN Jie-ran1 DU Jun-ting1 DING Shu-mao1

(1.Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Central China Normal University, Wuhan, China 430079)
【Knowledge Link】homogenate

【Abstract】To explore the combined toxic effect of formaldehyde (FA) and DEHP on learning and memory of mice and the mechanism, Kunming mice were randomly divided into 14 groups: (1) the control group; (2) FA group: 0.5 mg/m3, 1 mg/m3, 3 mg/m3; (3) DEHP group: 5 mg/kg, 50 mg/kg, 500 mg/kg; (4) the combined exposure: 0.5 mg/m3 + 5 mg/kg, 1 mg/m3 + 50 mg/kg, 3 mg/m3 + 500 mg/kg; (5) VE group: saline + VE (100 mg/kg), 3.0 mg/m3 FA + VE, 500 mg/kg DEHP + VE, 3.0 mg/m3 FA + 500 mg/kg DEHP + VE. The mice of FA and combined exposure groups were exposed to gaseous FA for 8 h every day (continuous exposure for 5 days, interval for two days), and the mice of DEHP and combined exposure groups were subjected to gavage with DEHP solution. Besides, blocking groups were also subjected to gavage with VE solution (100 mg/kg) every day. Their behaviors of learning and memory were tested by Morris water maze test. Then the changes of biological indicators including oxidative damage, ROS, MDA, TNF-α, IL-β, 5-HT, etc., in the cerebral tissue were detected. Results showed that Morris water maze test in space training and learning indicated that escape latency significantly extended in 3.0 mg/m3 FA and 500 mg/kg DEHP treatment group, 1.0 mg/m3 + 50 mg/kg and 3.0 mg/m3 + 500 mg/kg of the combined exposure groups (P < 0.05). Compared with single exposure groups, escape latency significantly extended in the moderate and high dose of combined exposure groups (P < 0.05). In space exploration experiments, the proportions of time of the target quadrant in 1.0 mg/m3 and 3.0 mg/m3 FA treatment groups, the 500 mg/kg DEHP treatment group, and 1.0 mg/m3 + 50 mg/kg, 3.0 mg/m3 + 500 mg/kg of the combined exposure groups were less than the control group (P < 0.05). The proportions of time of the target quadrant in combined exposure groups were significantly decreased compared with single exposure (P < 0.05). Compared with control group, the content of ROS and MDA in 1.0 mg/m3 and 3.0 mg/m3 FA, 50 mg/kg and 500 mg/kg DEHP groups and all the combined exposure groups was increased, while the content of GSH decreased in 3.0 mg/m3 FA, 500 mg/kg DEHP groups and all the combined exposure groups decreased. Compared with formaldehyde or DEHP exposure groups, the content of GSH in combined exposure groups was significantly decreased (P < 0.01). The expression levels of inflammatory factors TNF-α and IL-β were also significantly increased, and caspase-3 was activated. The content of 5-HT in 3.0 mg/m3 + 500 mg/kg of combined exposure group was significantly decreased (P < 0.01). 0.5 mg/m3 FA had little effect on mice and their behaviors of learning and memory did not obviously change. This study shows that 1.0 mg/m3 and 3.0 mg/m3 FA and 500 mg/kg DEHP treatment group and 1.0 mg/m3 + 50 mg/kg, 3.0 mg/m3 + 500 mg/kg of the combined exposure groups could cause oxidative damage and inflammation of Kunming mice. The combined exposure to FA 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.

【Keywords】 formaldehyde; DEHP; combined exposure; mice; learning and memory;

【DOI】

【Funds】 National Natural Science Foundation of China (21577045, 21507026)

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This Article

ISSN:1000-6923

CN: 11-2201/X

Vol 37, No. 12, Pages 4751-4762

December 2017

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Abstract

  • 1 Materials and methods
  • 2 Results
  • 3 Discussion
  • 4 Conclusions
  • References