The Effect Of DEHP On The Oxidative Stress And Lipid Metabolism In Liver Of Rats Fed With High-Fat Diet

Di-(2-ethylhexyl)phthalate(DEHP),commonly widely used as plasticizers,are found in many fields.DEHP enters the human body through the mouth,skin and respiratory tract,and also accumulates in the human body through the food chain.The liver is one of the main organs of DEHP.Previous studies have revealed that DEHP induces lipid peroxidation,oxidative stress and lipid metabolism disorder in the liver.However,the dose of DEHP used by researchers is generally more than 1000mg/kg bw,which is quite different from the dose of DEHP actually absorbed in daily life and is not representative.Furthermore,a high fat diet(HFD)causes oxidative stress and lipid metabolism.Therefore,the effects of DEHP combined with a HFD on oxidative stress and lipid metabolism in the liver were investigated by RT-PCR,biochemical analysis,enzyme linked immune sorbet assay and H&E staining,which could provide references for further research on the combined effect of DEHP and HFD on metabolic syndrome and its impact on human health.In this study,30 male SD rats were randomly divided into 5 groups(n=6).The control group was fed a normal diet.The other four groups fed a HFD were treated with different concentrations of DEHP(0,0.5,10 and 100 mg/kg bw)for 8 weeks by gavage.We found that 1)Statistical compared with the control group,DEHP plus HFD increased the body weight of rats,and aspartate transaminase(AST)and alanine aminotransferase(ALT)levels of liver function indexes in serum;liver weight,organ /body weight ratio of liver or epididymis adipose significantly increased of the 100mg/kg bw DEHP exposure group.AST / ALT ratio of reflecting hepatocyte injury is much higher than the normal range.2)Histomorphological observations revealed that no histological abnormalities were observed in the liver tissue of the control group.All rats given a HFD had hepatic steatosis to varying degrees,and DEHP-treated groups showed hepatocyte edema.High dose group showed mild inflammation,and some cells were broken.3)Contents of triglyceride(TG),total cholesterol(TC)and low-density lipoprotein cholesterol(LDL-C)in the serum were higher in DEHP plus a HFD group than in the control group;while the contents of high-density lipoprotein cholesterol(HDL-C)decreased compared with the control group.4)Compared with the control group,10mg/kg bw and 100mg/kg bw DEHP-treated groups increased the contents of malondialdehyde(MDA)and catalase(CAT)of liver in rats;protein carbonylation(PC)of reactive protein oxidative damage also showed an increasing trend,while superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in liver decreased.5)Relative m RNA expression of interleukin-6(IL-6)and tumor necrosis factor-?(TNF-?)in the liver were higher in DEHP plus a HFD group than in the control group;the m RNA expression of IL-6 and TNF-? in100mg/kg bw DEHP-treated group significantly increased than the control group.6)Compared with the control group,DEHP combined with HFD-treated groups showed higher free fatty acid(FFA)and glucose level,and lower insulin(INS)level.7)Compared with the control group,DEHP plus a HFD increased the m RNA expression of genes related to lipid synthesis in liver.Compared with the HFD group,10mg/kg bw and100mg/kg bw DEHP-treated groups significantly increased the m RNA expressions of sterol-regulatory element-binding protein(SREBP-1c)and fatty acid synthase(FAS).8)Relative m RNA expression of genes related to fatty acid oxidation and decomposition in liver were higher in DEHP combined with HFD groups than the control group.Compared with the 0.5mg/kg bw DEHP group,relative m RNA expression of carnitine palmitoytransferase 1(CPT-1)in the 10mg/kg bw and 100mg/kg bw DEHP groups decresed.9)Relative m RNA levels of hydroxymethylglutaryl coenzyme A reductase(HMGCR)and low-density lipoprotein(LDLR)were significantly lower in DEHP plus a HFD than the control group.Results showed that 1)Exposure to DEHP plus a HFD led to hepatocyte proliferation,and induced liver injure,which the degree of damage was getting worse with increasing DEHP dose.While DEHP plus a HFD led to dyslipidemia,oxidative stress and inflammation.2)Within the experimental DEHP dose range,DEHP combined with HFD may strengthen lipid synthesis which was mediated by SREBP-1c and fatty acid oxidation which was induced by peroxisome proliferator-activated receptor ?(PPAR-?).DEHP combined with HFD led to lipid disturbances and lipid deposition in liver of rats,which may be caused by a stronger lipid synthesis effect than a lipolytic effect.3)The interaction of oxidative stress,inflammation,and lipid metabolism may be an important cause of liverdamage in DEHP combined with HFD.Thus it increased the possibility of nonalcoholic fatty liver disease(NAFLD)and type 2 diabetes in rats.