Study On Neurotoxicity Effects And Mechanisms Of Joint Exposure To Formaldehyde And Toluene In Mice

Objective: In recent years, indoor air pollution caused by the interior decoration has become a hot issue for national, governments, businesses and consumers concerned. It is also a problem to be solved in the process of economic and social development. Aldehyde and benzene homologue are the main pollutants of indoor air pollution. The impacts characteristics on human health are long time, low dose and multiple interacting. Now there are lots of reports about neurotoxicity effects of formaldehyde or toluene, but few about joint exposure to both of them. The aim of this study is to explore the neurotoxicity effects and mechanisms of joint exposure to formaldehyde and toluene in mice, and provide the scientific evidence for preventing and curing the health effects caused by indoor air pollution.Methods: Seventy-two healthy and clean Kunming mice were screened by Morris water maze test. 3×3 factorial design was used in the experiment. The mice were randomly assigned into 9 groups. The control group (0mg/m~3 formaldehyde +0mg/m~3 toluene), formaldehyde group(1mg/m~3, 5mg/m~3), toluene group(400mg/m~3, 2000mg/m~3), combined group(1mg/m~3 formaldehyde +400mg/m~3 toluene, 1mg/m~3 formaldehyde + 2000mg/m~3 toluene, 5mg/m~3 formaldehyde +400mg/m~3 toluene, 5mg/m~3 formaldehyde +2000mg/m~3 toluene). The treatments were conducted by static inhaling formaldehyde or (and) toluene, two hours per day for 14 days consecutively. On the 15th day, their behaviors of learning memory were tested by Morris water maze and open field test. At the end, the activity of SOD and NOS, the contents of ROS, GSH and MDA in brain of the mice were detected. The DNA damage in brain cells of mice was detected by comet assay and KCl-SDS precipitation.Results: 1. Formaldehyde and toluene exposure could lead to degeneration in learning and memory abilities of mice. (1) The results of Morris water maze test showed in space training and learning experiment, the escape latency of all groups increased as the exposure dose increased and decreased as the days of training increased. Days of training, formaldehyde and toluene were statistically significant to escape latency (P<0.05). In space exploration experiment, the time of finding the platform presented an ascend tendency, while the time and the percentage of swimming distance in target quadrant presented a descend tendency (P<0.01). There is interaction between formaldehyde and toluene in the time of finding the platform (P<0.05). (2)The results of open-field test showed the latency presented an ascend tendency, the number of crossing pane, standing and modifying presented a descend tendency (P<0.01). There was interaction in latency, the number of crossing pane and standing between formaldehyde and toluene (P<0.05). 2. Compared with the negative control group, formaldehyde and toluene exposure could cause the oxidation damage of brain tissue of mice. The contents ROS and MDA, the activity of NOS in brain were increased, while the contents of GSH and the activity of SOD were both decreased significantly (P<0.05). There was interaction between formaldehyde and toluene of ROS, NOS, SOD, GSH and MDA in mice (P<0.01). And the joint toxic effect exhibited synergistic effect.3. Compared with the negative control group, formaldehyde and toluene exposure could cause the DNA breakage and DNA-Protein crosslink in brain cells of mice. The results of factorial analysis indicated an interaction in DNA damage between formaldehyde and toluene. And the joint toxic effect to DNA damage showed a synergistic joint action.Conclusion: Formaldehyde and toluene had neurotoxicity to mice of single or joint exposure. They can degrade the learning and memory abilities and then affect the neurobehavioral function of mice. Also they can result in lipid peroxide in brain tissue and the DNA damage in brain cells of mice. The joint neurotoxicity effect of formaldehyde and toluene is synergistic. The lipid peroxide and DNA damage may be the important mechanisms of central nervous system function damage in mice induced by formaldehyde and toluene.