DEHP plasticizer-induced hepatotoxicity in rats:elevated reactive oxygen species levels as a mechanism
Objective To investigate the hepatotoxic effects of the plasticizer DEHP and explore its potential mechanism involving the elevation of reactive oxygen species.Methods A total of 50 Sprague-Dawley rats were randomly divided into five groups:blank control,vehicle contro,DEHP low dose(1 mg/k),DEHP medium dose(5 mg/kg),and DEHP high dose(25 mg/kg).Body weight was monitored during the treatment period.At the end of the treatment,serum biochemical indices,liver coefficients,and oxidative/reductive indices in hepatic tissues were measured.Human normal hepatocytes HL-7702 were divided into blank control,vehicle control(DEHP 0 μmol/L)and experimental groups(DEHP 0.1 μmol/L,10 μmol/L and 100 μmol/L).Cell viability was assessed at 24 h,48 h and 72 h,along with measurements of TG,TC and ROS levels,and the expression of genes and proteins related to the Nrf2/HO-1 signaling.Results(1)The body weights of rats in the DEHP low dose,middle dose and high dose groups decreased in a dose-dependent manner during the 1st 2nd and 4th weeks post-treatment(P＜00.05).(2)At the end of treatment,the liver weight and liver coefficient of rats in the DEHP low dose,medium dose and high dose groups increased in a dose-dependent manner compared to the vehicle control group(P＜0.05).(3)Serum AST,ALT and ALP levels in the DEHP low dose,medium dose,and high dose groups were elevated in a dose-dependent manner compared to the vehicle control group at the end of the treatment period(P＜0.05).(4)The levels of ROS and MDA in hepatic tissues of rats in the DEHP low dos,medium dose,and high dose groups increased in a dose-dependent manner,while the levels of SOD and GSH decreased in a dose-dependent manner at the end of treatment(P＜0.05).(5)The viability of HL-7702 cells in the DEHP medium dose and high dose groups decreased in a dose-dependent manner compared to the vehicle control group at 24 h,48 h,and 72 h post-cultivation(P＜0.05),(6)The levels of TG,TC and ROS in HL-7702 cells in the DEHP medium dose and high dose groups increased in a dose-dependent manner(P＜0.05).(7)The mRNA expression levels of Nrf2,HO-1 and NQO1 in HL-7702 cells decreased in a dose-dependent manner in the DEHP medium dose and high dose groups(P＜0.05).(8)The protein expression levels of Nrf2,HO-1 and NQO1 in HL-7702 cells decreased in a dose-dependent manner in the DEHP medium dose and high dose groups(P＜0.05).Conclusion Plasticizer DEHP exhibits hepatotoxicity,potentially through oxidative stress injury in the liver by modulating the Nrf2/HO-1 signal pathway to increase reactive oxygen species levels.
DEHPOxidative stressLiverReactive oxygensignal pathway of Nrf2/HO-1
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