Intervention Effects Of LBP And Lycium Barbarum Juice On Acute Liver Toxicity Induced By DEHP Exposoure In Rats

In this study, regulation effects of LBP and Lycium barbarum juice on acute liver toxicity induced by DEHP exposoure in rats were observed through both pre-exposure and post-exposure interventions. 40 SD male rats were randomly divided into5 groups in pre-exposure intervention trial: control group, DEHP group, LBP low, medium and high intervention group. DEHP exposure dose was 2000 mg/kg and LBP intervention doses were 50,100,200 mg/kg.bw. The animals were orally administrated with LBP for 6days, and then at the same time in the seveth day of intervention, the DEHP group and 3intervention groups were gavaged with DEHP. All rats were sacrificed in 24 hours after DEHP exposure. 80 SD male rats were randomly divided into 4 groups in post-exposure intervention trial after exposure: control group, DEHP group, LBP intervention group and lycium barbarum juice intervention group. DEHP exposure dose was 3000 mg/kg, LBP intervention doses were 200 mg/kg.bw and lycium barbarum juice intervention doses were8 ml/kg.bw. In the first day of intervention, the DEHP group and 2 intervention groups were gavaged with DEHP, intervention groups were orally administrated with LBP or lycium barbarum juice for 7 days. At 1 3, 5 and 7 days after exposure, 5 rats of each group were killed randomlly. The metabolic enzymes, transcription factors and oxidative stress indexes in rat livers were detected for acute exposure to DEHP. The specific results as follows:(1) Pre-exposure intervention trialDEHP exposure caused the liver enzymes CYP2E1 and CYP3A1 activity decreased(P<0.01), CYP1A1 activity decreased, enzymes GSTpi and UGT1 activity decreased(P<0.05), LBP high dose intervention group could increase CYP2E1 activity(P<0.01),CYP3A1 activity(P<0.05), CYP1A1 activity(P<0.05), GSTpi activity(P<0.05) and UGT1activity(P<0.05) of exposured rats.DEHP exposure increased MEHP levels in rat serum,MEHP and PA levels in urine. LBP intervention could reduce MEHP levels in rat serum and increase MEHP and PA excreted in urine.DEHP exposure caused the phase ? and ? metabolic enzymes activity decreased,DEHP metabolism slown down and the accumulation of MEHP increased. LBPintervention could increase the activity of phase ? and ? metabolic enzymes, reduce intermediate metabolite MEHP accumulate in the blood, increasing MEHP and PA excreted in the urine.(2) Post-exposure intervention trial(1)Effect of general toxicity on rats: Liver coefficient in DEHP group was higher than control group from first to fifth days(first day, P<0.01; third day, P<0.01) and then close to normal levels. Testis coefficient in DEHP group was lower than control group from first to fifth days(third day, P<0.01; fifth day, P<0.01)and then close to normal levels. LBP and lycium barbarum juice intervention could decrese rats' liver coefficient and increased testicular coefficient.(2) Effect on oxidative damage in rats: SOD activity in serum in DEHP group were lower than control group from first to third days( third day, P<0.01) and then close to normal levels. GSH-Px activity in serum of DEHP group was lower than control group from first to third days( third day, P<0.05) and then close to normal levels. LBP and lycium barbarum juice intervention could increased the SOD and GSH-Px activity( third day, P<0.01). SOD activity in liver of DEHP group was higher than control group(first,third and fifth day, P<0.01) while GSH-Px activity in liver in liver of DEHP group was higher than control group( first and third day, P<0.05). MDA levels were significantly elevated after exposure to DEHP in third and seventh day(P<0.05). Lycium barbarum juice intervention could decrease rats' liver SOD activity(third and fifth day, P<0.01), GSH-Px activity(third day, P<0.01; fifth day, P<0.05)and MDA levels(third day, P<0.01; seventh day, P<0.05). LBP intervention could increase SOD activity, GSH-Px activity and MDA levels.(3)Effects of enzymes on hepatic metabolism in rats: DEHP exposure caused the liver cytosol GST activity increased(P<0.05), liver microsomal GSTpi and UGT1 activity decreased. Lycium barbarum juice intervention increased the UGT1 level in the fifth day(P<0.05).(4)Effects of transcription factors in rats: PXR activity increased(P<0.05 or P<0.01)from third to fifth day, and decreased in the seventh day. LBP intervention increased the PXR activity in the first and third day(P<0.05), and decreased from fifh to seventh day.Lycium barbarum juice intervention caused the PXR activity dowand, and decreased thePXR activity(P<0.05)in the fifth day.(5)Effects of DEHP on the metabolism of rats: After exposure to DEHP, the content of rat serum MEHP decreased with time and no MEHP was detected in the seventh day. LBP intervention could reduce MEHP levels in the serum and no MEHP was detected in the fifth day. Lycium barbarum juice intervention could reduce MEHP levels in the serum and no MEHP was detected in the third day. LBP and Lycium barbarum juice intervention can increase the rate of excretion of urinary MEHP. Similarly, the excretion rate of PA in rat urine decreased with time after exposure to DEHP. LBP and Lycium barbarum juice intervention can increase the rate of excretion of urine PA.DEHP exposure caused the PXR activity increased, RXR? activity decreased first and then increased. DEHP exposure activated PXR and decreased GSTpi activity, slowed down DEHP metabolism and increased the accumulation of MEHP and caused oxidative damage.LBP intervention could reduce the accumulation of intermediate metabolite MEHP in the blood and led to increase of MEHP and PA excretion in the urine.