Study On Liver Damage Induced By Dimethylformamide To Workers And Vitamin E Intervene Experiment

BackgroundDimethylformamide (DMF) is an important organic material, widely used in fiber-making, leather-synthetizing, medicine-making and other industrial production. With the development of modern industry, the consumption of DMF is growing, and the occupational population exposed to DMF is expanding, and the reports on occupational DMF poisoning are increasing. Animal experiments showed that DMF have hepatotoxicity, and it could cause acute and chronic liver injury. Occupational epidemiological survey found that the incidence of liver function abnormality of DMF exposure workers was increased, and there was report on severe chronic liver disease caused by DMF interiorly. Therefore, it is necessary to explore the condition of liver damage induced by DMF to workers and to find its related factors, and to put forward prevention measures.Research found, DMF could cause glutathione (GSH) level decrease in vivo and organism antioxidant ability decline, which was associated with liver damage. Vitamin E (VE) has oxidation resistance function, animal experiments and clinical applications showed that it had good effect to protect the liver. Also, cell experiments demonstrated that VE could significantly increase the GSH level in cells, Therefore, using VE to prevent liver damage induced by DMF was considerable.ObjectiveThe present study is aiming to observe the condition of liver damage induced by DMF to workers and explore the related factors, and to conduct VE intervene experiment on animals, and to put forward measures to prevent liver damage induced by DMF.Methods1. Investigation of liver damage induced by DMF to workersChose152workers exposed to DMF as exposure group and179unexposed workers as control group in an acrylic factory, to carry out occupation health questionnaire. Collected the DMF monitoring data and workers’health care information, analysis the condition of liver damage induced by DMF and explore the related factors.2. VE intervene experimentAcute experiment:SPF level of healthy male Kunming mice, were randomly divided into5groups, with10mice in each group, which were control group (corn oil by gavage for5days+distilled water by gavage for1days), the VE control group (10mg/kg· d VE by gavage for5days+distilled water by gavage for1days), DMF poisoning model group (corn oil by gavage for5days+2g/kg· d DMF by gavage for1days) and low (5mg/kg·d), high (10mg/kg·d) doses of VE intervention group (VE by gavage for5days+2g/kg· d DMF by gavage for1days).Subchronic experiment:SPF level of healthy male Kunming mice, were randomly divided into4groups,10mice in each group, which were control group (distilled water+corn oil), VE control group (distilled water+5mg/kg·d VE), DMF poisoning model group (0.5g/kg· d DMF+corn oil) and VE intervention group (0.5g/kg· d DMF+5mg/kg· d VE), with intervention of30consecutive days.Observe the changes of activity of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and xanthine oxidase (XOD); Observe the changes of content of liver GSH and malondialdehyde (MDA); Observe the pathological changes of the liver.Results1. Investigation of liver damage induced by DMF to workers ①ompared with the control group, the incidence of liver damage for exposure group was significantly increased (P<0.05), Mainly for the incidence of liver function abnormality was significantly increased(P<0.01):the incidence of ALT abnormality of exposure group was significantly higher than that of the control group (P<0.01), and the incidence of glutamyltransferase (GT) abnormality of exposure group was significantly higher than that of control group (P<0.01). The incidence of liver B ultrasound abnormality was higher than that of the control group in the trend, but the difference was not statistically significant (P>0.05).②Risk factors of liver damage induced by DMF to workers were the DMF concentration(OR=1.07, P<0.05), DMF exposure time (OR=1.06, P<0.05) and body mass index (OR=1.10, P<0.05). Thereinto, risk factors of ALT abnormality were DMF concentration(OR=2.21, P<0.05) and body mass index (OR=1.14, P<0.05); Risk factors affecting the incidence of GT abnormality were DMF concentration (OR=2.62, P<0.01), DMF exposure time (OR=1.11, P<0.05) and alcohol (OR=3.91, P<0.01); But, risk factors affecting the incidence of liver B ultrasound abnormality was only body mass index(OR=1.19, P<0.01).2. VE intervene experimentAcute experiment:①Compared with the control group, liver weight and liver coefficient of poisoning model group increased significantly (P<0.01); Compared with the control group, the liver weight and liver coefficient of VE intervention group had no statistically significant difference(P>0.05); Compared with the poisoning model group, the liver weight and liver coefficient of VE intervention group decreased significantly (P<0.05).②ompared with the control group, the activity of serum ALT, AST and XOD of poisoning model group were significantly increased(P<0.05); Compared with the control group, the activity of serum ALT, AST and XOD of VE intervention group had no statistically significant difference(P>0.05); Compared with the poisoning model group, the activity of serum ALT, AST and XOD of VE intervention group decreased significantly (P<0.05).③Compared with the control group, the content of liver GSH of poisoning model group decreased significantly (P<0.05), but the content of liver MDA was significantly increased (P<0.01); Compared with the control group, the content of liver GSH of VE intervention group had no statistically significant difference(P>0.05), but the content of liver MDA was significantly increased (P<0.01); Compared with the poisoning model group, the content of liver GSH of VE intervention group was significantly increased (P<0.05), and the content of liver MDA decreased significantly (P<0.01).④Liver pathological sections of poisoning model group showed liver cells of focal necrosis, inflammatory cell infiltration, hepatic sinusoid dilation, congestion, hemorrhage; Liver pathological sections of VE intervention group showed normally.Subchronic experiment:①Compared with the control group, body weight of poisoning model group and VE intervention group were significantly lower (P<0.01), but the liver coefficient were significantly increased (P<0.01).②ompared with the control group, the activity of serum ALT, AST and XOD of poisoning model group and VE intervention group were significantly increased (P <0.05); Compared with the poisoning model group, the activity of serum ALT, AST and XOD of VE intervention group decreased significantly (P<0.05).③Compared with the control group, the content of liver GSH of poisoning model group decreased significantly (P<0.01), but the content of liver MDA was significantly increased (P<0.01); Compared with the control group, the content of liver GSH and MDA of VE intervention group were significantly increased (P<0.01); Compared with the poisoning model group, the content of liver GSH of VE intervention group was significantly increased (P<0.01), and the content of liver MDA decreased significantly (P<0.05).④Liver pathological sections of poisoning model group showed hepatocyte nuclear pyknosis, perinuclear vacuoles, cell edema, degeneration, necrosis, unclear cell boundary; Liver pathological sections of VE intervention group showed normally.Conclusions1. The incidence of liver damage for DMF exposure workers was significantly increased, mainly for the incidence of liver function abnormality was significantly increased, and the incidence of liver B ultrasound abnormality changed indistinctively.2. Related factors of liver damage induced by DMF to workers were DMF concentration, DMF exposure time, body mass index and alcohol.3. VE could reduce the levels of serum liver function enzyme in mice with DMF poisoning, and alleviate the pathological damage, and protect the liver.4. VE could improve the level of GSH and decrease the level of MDA in mice with DMF poisoning, which may be a mechanism for VE to protect the liver.5. We proposed DMF concentration in the air of workplace should be decrease and DMF exposure time should be shorten; Also we advocated workers should control weight and reduce alcohol, and should supplement VE in the diet, to prevent liver damage induced by DMF.