Experimental Study On ICR Mice Subchronic Exposure To N, N-dimethylformamide

Objective To explore the subchronic toxicity of N,N-dimethylformamide (DMF) to heart and liver and the effects on neurobehavior subchronic exposure to DMF in ICR mice.Methods Eighty ICR mice were treated with DMF though oral exposure at 1.26, 0.63, 0.32 g/kg/d and normal saline respectively for 90 days. 40 mice were sacrificed after 50th and 90th day of treatment respectively. the concentration of alanine transarninase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH) , isoenzymes of creatine kinase (CK-MB) and alpha-hydroxybutyric dehydrogenase (α-HBDH) in serum were examed, as well as the concentration of superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) in liver and heart. Before and after 50 and 90 days of exposure, the mice's behaviors were monitored by morris water maze test, avoiding dark box experiment and shuttle-box test, autonomic activity test.Results After 50 days of treatment, the levels of ALT, AST in serum didn't changed significantly, and the concentration of NO was significant more in liver of low dose group than those of control group (P<0.05) , After 90 days of treatment, the levels of ALT in serum was significantly higher in high dose group than those of control group, and the contents of NO, SOD and MDA in liver was significant more in high group as well (P<0.05) . the level of CK-MB elevated significant more in high dose group and low dose group than those of control group and middle group (P<0.01 or P<0.05) , the levels of MDA elevated significantly in heart of middle dose group and low dose group than those of control group (P<0.01 or P<0.05) . After 90 days of treatment, the levels of LDH,α-HBDH in serum was higher in middle dose group than those in control group (P<0.05) . The contents of SOD decreased more significant in heart of middle group than those of control group(P<0.05). After 50 days of exposure, the latence time of morris maze was longer in groups received 1.26 g/kg/d DMF than before, and there is significant difference (P<0.05); The results of avoiding dark box test shows that the number of electric shocks in highest exposure groups was more than those in control group, and the latence time in the highest exposure groups was shorter than those in control group. There is significant difference between the two groups (P<0.05); The shuttle-box experiments shows that the number of electric shocks in exposure groups was more than those in control group, and there is significant difference between the highest exposure group and control group(P<0.05); The active escape time in exposure groups was longer than those in control group, and there is significant difference between 1.26 g/kg/d DMF exposure group and control group (P<0.01); Autonomic activity box test shows that autonomic activities in exposure groups was more than those in control group, and it was significant more in received 1.26 g/kg/d DMF group than those in control group(P<0.05). After treated for 90 days, the number of electric shocks increased (P<0.05) and the active escape phase shorter (P<0.01) in highest dose group when contrasted with the control group in shuttle-box tests, the number of autonomic activities increased in highest dose group when contrasted with the control group (P<0.05) and there was a negative dose-response relationship(P<0.05)between the number of autonomic activities and the exposed doses in autonomic activity box tests.Conclusions The damage to mice's livers caused by DMF is significant; DMF dose some harm to hearts in mice; DMF can increase the levels of lipid peroxidation. the damage to heart. There may be certain relevance between damage of liver and the elevation of lipid peroxidation. subchronic exposure to DMF has a certain effect on learning and memory while on central nervous system(CNS) it characterized as being excited first and then depressed.