| Di-(2-ethylhexyl)phthalate(DEHP)is one of common pollutants of PAEs which has been widely used in medical devices,food wraps,cosmetic products,paint,and chemical synthesis.It could be released from the plastic into environment.Human beings may expose to DEHP through respiratory,digestive tract and skin.And it could adversely affect human health.Previous research about the toxicity of DEHP were more focused on reproductive toxicity and embryo genetic toxicity.But there are few reports about the toxicity of DEHP on liver biotransformation.The fruit of Lycium barbarum,also called Goji berry or wolfberry,is a well-known traditional C hinese herbs,which has effect of anti-aging.Some studies indicated that Lycium barbarum Polysaccharide(LBP),which is the main active component,had the effects of relieving oxidative stress.The study was designed to investigated whether the LBP could alleviate the toxicity of liver induced by DEHP in rats on the basis of our preliminary studieson DEHP and Lycium barbarum.First of all,DEHP [300,1000,3000 mg/(kg·bw)] were orally administrated to SD rats respectively over a period of 28 days.Rats in the control group were gavaged by corn oil in same volume.O xidation indices in serum and liver and biotransformation enzymes such as phase I and phase II enzymes were measured.MEHP and PA were detected by High performance liquid chromatography(HPLC).Secondly,LBP [50,100,200 mg/(kg·bw)] and Chinese wolfberry juice [equal to 25,50,100 mg/(kg·bw)LBP] were orally administrated to SD rats respectively over a period of 28 days.Rats in the control group were gavaged by salinein the same volume.The health care effects of LBP were evaluated by measuring the oxidation indices and liver biotransformation enzymes levels.Thirdly,further research was carried out to investigate the potential protective effect of LBP on DEHP-induced hepatotoxicity in rats.SD rats were divided into control group(corn oil),LBP group [300 mg/(kg·bw)],DEHP group [3000 mg/(kg·bw)],and LBP-DEHP groups [100,200,300 mg/(kg·bw)LBP + 3000 mg/(kg·bw)DEHP].The intervention effects were evaluated by oxidation indices in serum and liver,phase I and phase II enzymes levels.HPLC method was used to detect the levels of MEHP and PA in serum and urine.The detoxification mechanism of LBP on DEHP-induced liver toxicity was explored by the signal pathway of pregnane X receptor(PXR).Statistical data analysis were carried out using SPSS 23.0.The main research results were as follows:(1)The general toxicity of DEHP in rats: Compared with control group,the rats in high dose DEHP group had a slower growthrate.The body weight and food utilization rates declined significantly(P<0.01).DEHP exposure in different doses of caused the liver and kidney coefficients increased while the the weight coefficient of testis decreased(P<0.01).(2)The effects on oxidation system of DEHP in rats: The activity of SOD and GSH-Px in serum and liver of high dose DEHP were lower than control group(P<0.05),while the MDA increased(P<0.05 or P<0.01).The content of 8-iso-PGF2? in liver of medium and high dosage groups was significantly elevated(P<0.05).Liver pathological lesions to different degrees were observed in each dosage groups and were positively correlated with the dosage.(3)The influence of DEHP on biotransformation enzymes of liver and metabolic change: The contents of CYP450,CYP2E1 and CYP3A1 were significantly increased compared with control group(P<0.05 or P<0.01),which were positively related with the dosage of DEHP.The content of GST-pi,protein kinase A(PKA),protein phosphatase(PP)and PXR increased in all the dosage groups of DEHP caused to,as well as GST in high dose group(P<0.05 or P<0.01).The content of UGT1 elevated in medium and high dose exposure groups(P<0.01).The level of MEHP in serum elevated significantly in medium and high dose groups compared with control group(P<0.01).The contents of MEHP and PA in urine were the highest on the 7th day,and then decreased.(4)LBP and Chinese wolfberry juice had no significant difference in rats except the activity of GSH-Px in serum.The activity of GSH-Px in serum of high dose group was significantly increased(P>0.05).(5)The intervention effect of LBP on general toxicity of DEHP: The body weight,total food utilization rate and testis coefficient of each LBP dosage intervention group were higher than only DEHP-treated group(P>0.05),while the liver and kidney coefficients were lower(P>0.05).(6)The regulation effect of LBP on oxidation system of DEHP : Declined ROS,increased the activities of GSH-Px and SOD in serum and liver were observed with administration of LBP interventions(P>0.05)(7)The regulation effect of LBP on biotransformation enzymes in rats exposed to DEHP: A marked decrease of CYP450,CYP2E1 and C YP3A1 content were observed in liver when just only compared with DEHP-treated group(P<0.05).The contents of UGT1,GST,GST-pi,PKA,PP and PXR had a certain degree of decrease but no significant differences.(8)The regulation effect of LBP on PXR and its downstream phase II detoxifying enzymes genetic expressions: Compared with DEHP group,each dosage of LBP down-regulated the mRNA expression of PXR,GST and UGT1 and the high dose group had a significant difference(P<0.05).(9)The influence of LBP on metabolism in rats exposed to DEHP: The level of MEHP in serum and urine of each LBP intervention groups was lower than DEHP-treated group(P<0.05 or P<0.01).The level of PA in urine on 7th day was higher than DEHP-treated group(P>0.05).The above results indicated that DEHP had liver toxicity of oxidative damage.LBP may reduce the toxicity by regulating levels of phase I,phase II and mRNA expression through PXR signal pathway in the rats exposed to DEHP,though Chinese wolfberry juice and LBP had few significant influence on normal rats. |
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