Study On The Mechanism Of DEHP-induced Liver Lipid Metabolism Disorder In Quail

As a plasticizer,di-2-ethylhexyl phthalate(DEHP)has been widely used in many fields(agricultural products,medical instruments,and food packing).It cause serious pollution to the atmosphere,water,soil and food,and has become an important environmental pollutant.DEHP has estrogenic effect and has toxic effects on endocrine system,reproductive system and nervous system.The liver is not only the most important detoxification organ of the body,but also one of the main target organs of DEHP toxicity.However,there are few studies on the hepatotoxicity of DEHP in birds.Therefore,in this study,300 healthy male quail were randomly divided into 5groups(60 quails in each group)and treated as follows:(n = 60): Con group(control group)、VCon group(vehicle control group)、D250 group(250 mg/kg DEHP group)、D500 group(500 mg /kg DEHP group)、 D750 group(750 mg/kg DEHP group),continuous exposure by intragastric administration for 45 days.We observed liver histopathology and oil red O staining changes.The levels of TG,TC,LDL-C and HDL-C in serum,the contents of TG and TC in liver,the expression of lipid metabolism and inflammatory related factors were measured.The results showed that:(1)DEHP exposure could increase the level of serum lipid(TG,TC,HDL-C,LDL-C)and increase the content of TG and TC in liver.The results suggested that DEHP exposure could lead to the lipid metabolism disorders in quail liver and lead to the accumulation of lipids in the liver.(2)Histopathological observation showed that DEHP exposure led to liver swelling and degeneration,liver plate rupture,abnormal cell structure and disorder.Liver steatosis and inflammatory cells infiltration were observed in DEHP exposured groups.The results of oil red O staining showed that lipid droplets in the liver significantly increased after DEHP exposure.(3)DEHP exposure up-regulated the expression of key genes regulating lipid metabolism,including LXR(ABCA1,ABCG1,CYP7A1),SREBP-1c(ACC,ACLY,SCD,FASN),FXR(SHP,SLC51 A,SLC51B),PPAR α(ACOX1,CPT1 A,EHHADH)and PPARγ(CD36,DGAT2,FABP4,MOGAT1).Results suggested that DEHP causes lipid metabolism disorder in quail liver by interfering with the expression of lipid metabolism molecules LXR,SREBP-1c,FXR,PPARα and PPARγ and their target genes,which may be one of the mechanisms of hepatotoxicity induced by DEHP.(4)After exposured to DEHP,NF-κ B signal pathway was activated in quail liver,which induced the increased expression of inflammatory cytokines(IL-6,TNF-α,IL-1 β and IL-8),and caused inflammatory reaction,suggesting that inflaingmmation could be one of the mechanisms of quail liver injury induced by DEHP.To sum up,DEHP exposure resulted in dyslipidemia,accumulation of TG and TC in the liver,oxidative damage,steatosis and inflammatory cells infiltration in the liver.The results suggested that DEHP may cause lipid metabolism disorder and inflammation through regulating LXR,SREBP-1c,FXR,PPARα,PPARγ and NF-κB signaling pathways.