Expression Of PPARs In The Liver Damage Induced By Tirchloroethylene Intake Via Drinking Water

Backgroud Trichloroethylene(TCE) is an organic solvent that has been widely used inindustry, because of the large number of applications but a limited ability to dispose it,huge amounts of TCE have been add to the atmosphere, soil and groundwater system asone of the environmental pollutants. The long-term low-dose exposure to TCE cancause hepatotoxicity and the imbalance of the body’s immune system. Studies show thatafter the liver metabolism, TCE generate metabolites that have the characteristic ofperoxisome proliferator(PP), and then activate the peroxisome proliferator activatedreceptors(PPARs), PPARs are related to the hepatotoxicity and immune responseinduced by environmental toxicologist, but the the expression of PPARs and themechanism of action in the liver damage induced by trichloroethylene via drinkingwater is still fully unknown.Objective By detecting the the liver damage induced by trichloroethylene via drinkingwater and expression of PPARs in mice liver，to discuss the expression of PPARs in theliver damage induced by trichloroethylene in the different times and different doses,and analyze the relation between PPARs expression and liver damage induced bytrichloroethylene, to provide theoretical basis for the hazards and molecularmechanism of TCE exposure.Methods The healthy female BALB/c mice (16~20g) were fed in experimental animalroom, the mice were randomly divided into blank control group, vehicle control group,2.5g/L TCE group and5.0g/L TCE group after the mice were allowed to acclimatefor one week, and exposed to TCE via drinking water, TCE was dissolved byDMSO(less than1%). On the2nd,4th,8th,12th week, drawing the blood from eyeballof mice, the serum was segregated for cryopreserving, the liver tissue was taken afteranimal were killed. The ALT was detected by fully automatic biochemical analyzer, liver tissues were taken for HE staining, the proinflammatory cytokine IL-1,IL-6,TNF-α in liver were measured by ELISA, The PPARα and PPARγ expressionin liver were measured by RT-PCR and immunohistochemical staining. The spss17.0was used for data entry and analysis.Result1The general case: Mice were in good condition and have no deaths during the TCEexposure, there were no significant difference in the average water consumption,weight gain and liver coefficient in different time point(P＞0.05).2The liver damage induced by TCE intake via drinking water: The levels of ALT in2.5,5.0g/L TCE treated groups increased significantly compared with control groups onthe2nd,4th week(P <0.05，P <0.01), ALT levels of TCE treated groups gone downon the8th,12th week, but still higher than the control group, the levels of ALT in5.0g/L TCE treated groups increased significantly compared with control groups on the8th week(P <0.05，P <0.01). HE staining showed inflammatory cell infiltration andcell degeneration in TCE treated groups, the damage was most obvious on the4thweek. The contents of liver IL-1, IL-6, TNF-α in2.5g/L and5.0g/L TCE treatedgroups all reached the highest on the4th weeks compared with control groups (P <0.05，P <0.01), the contents of liver IL-6and TNF-α in5.0g/L TCE treated groupsincreased significantly compared with control groups on the2nd,8th week, thecontents of proinflammatory cytokine gone down on the12th week, but still higherthan the control group. There was significant correlation between the level ofproinflammatory cytokine and ALT(r=0.615，0.522，0.649，p <0.01).3The expression of PPARs in mice liver: PPARα mRNA expression in liver of TCEtreated groups increased significantly on the4th,8th,12th week compared with controlgroups(P <0.05，P <0.01), there is no significant effect on the expression of PPARβmRNA(P＞0.05), on the4th week, the level of PPARγ mRNA in TCE treated groupsincreased significantly(P <0.05), so was the5.0g/L TCE treated groups on the8th, 12th week(P <0.05，P <0.01). in the nuclei of liver cells, the immunohistochemicalstaining showed that the expression of PPARα and PPARγ was positive in TCE treatedgroups, and the levels of PPARα and PPARγ expression in nuclei increased significantlycompared with control groups on the2nd,4th,8th,12th week(P <0.05).Conclusion1TCE exposure via drinking water induced liver damage in mice, the levels of ALTin serum and proinflammatory cytokine IL-1, IL-6, TNF-α in liver all increased,pathological examination showed obvious inflammatory cell infiltration, slightly edemaof some liver cells, and degeneration or necrosis in a few cells.2TCE exposure via drinking water had a significant impact on PPARα and PPARγexpression, PPARα and PPARγ were activated, PPARα and PPARγ mRNA increasedsignificantly.3The upregulation of PPARα and PPARγ may relate ro the liver damage induced bytrichloroethylene intake via drinking water.