Effects of combined treatment with diethylhexyl phthalate and bisphenol A on hepatic injury and oxidative stress in rats liver / 中国职业医学

ABSTRACT

OBJECTIVE: To observe the hepatic injury induced by combined exposure to diethylhexyl phthalate( DEHP) and bisphenol A( BPA) in rats and explore the mechanism of oxidative stress. METHODS: Thirty-two specific pathogen free healthy male SD rats were randomly divided into control group,DEHP(750 mg/kg body weight) group,BPA(100 mg/kg body weight) group and combined exposure group,with 8 rats in each group. The rats were gavaged once per day,7 days per week,for 6 weeks. The changes of liver organ coefficient and histopathology were observed. The activities of superoxide dismutase( SOD), glutathione peroxidase( GSH-Px) and the levels of hydrogen peroxide( H2 O2),malondialdehyde( MDA) were detected by spectrophotometry. The relative mRNA expression of antioxidant gene nuclear factor erythroid-2 related factor 2( Nrf2),heme oxygenase-1( HO-1),glutamate cysteine ligase catalytic subunit( Gclc),thioredoxin reductase( Txnrd),superoxide dismutase 3( Sod3) and glutathione peroxidase 1( Gpx1) in liver tissue were examined by real-time fluorescent quantitative polymerase chain reaction. RESULTS: The body weight of DEHP exposure group was lower than that of control group from the beginning of the 2 nd week( P < 0. 05),and the body weight of combined exposure group was lower than control group from the beginning of the 3 rd week( P < 0. 05). The liver mass and organ coefficients in DEHP group and combined exposure group were significantly higher than that of control group( P <0. 05). The results of pathology examination showed that there was necrosis of liver cells in DEHP group,vacuolar degeneration in cytoplasm of BPA group,and severe inflammatory cell infiltration in combined exposure group. The activity of SOD and GSH-Px of each exposure group was reduced( P < 0. 05),the H2 O2 level of each exposure group was increased(P < 0. 05),meanwhile the MDA level in the liver tissue of the BPA group and the combined exposure group increased compared with the control group( P < 0. 05). The relative mRNA expression of Nrf2,HO-1 and Gpx1 in each exposure group were decreased( P < 0. 05),the relative mRNA expression of Gclc,Txnrd and Sod3 in DEHP group and mixed exposure group were decreased compared with the control group( P < 0. 05). The relative mRNA expression of Nrf2,HO-1,Gclc,Txnrd and Sod3 in combined exposure group were decreased compared with the BPA group( P < 0. 05).CONCLUSION: Under the conditions of this study,DEHP and BPA alone or in combination could cause hepatic injury. The combined effect was greater than single effect. The effect of DEHP was greater than that of BPA. The liver injury induced by DEHP and BPA was related to Nrf2 signaling pathway.