Amelioration Of Perfluorooctanoic Acid In Utero Exposure Induced Hepatotoxicity In Female Offspring Mice By Lycium Barbarum Polysaccharide

Perfluorooctane acid(PFOA)is a new type of persistent organic pollutant that is widely used in daily life,such as non-stick pans,foam fire extinguishers,outdoor jackets,and paints.It accumulates in living organisms and seriously affects animal and human health.Especially during sensitive pregnancy,it will affect the survival and growth of the offspring.Lycuim barbarum polysaccharide(LBP)is the main active ingredient of Chinese herbal medicine,which has good effects in anti-oxidation,immune regulation and liver protection.In this study,the injury model of PFOA exposed to pregnant mice was constructed to investigate the effect of PFOA on liver injury in female offspring and the mechanism of LBP mitigation.In the PFOA modeling test,the pregnant females were randomly divided into 5 groups,10 in each group.The control group was given 0.2 mL of deionized water every day on gestation day(GD)1~17,and the other 4 groups were given 0.2 mL of different doses(1.0,2.5,5.0,10.0 mg/kg)of PFOA every day.The liver was collected and serum was separated on postnatal day(PND)21.The activities of AST,ALT,HAT and HDAC were detected by enzyme activity kit.The antioxidant enzymes and oxidation products were detected by ELISA.The expression of fatty acid oxidation related enzymes was detected by qPCR method.The histone acetylation level was detected by Western blot.The results showed that the number of births and survival of offspring in 80 mg/kg LBP group were significantly higher than that of the PFOA model group on PND 21,and the liver index was significantly decreased(P<0.05).The liver index of the 120 mg/kg LBP group was significantly decreased(P<0.01).HE staining showed that the area of liver necrosis was reduced in the LBP treatment group,and the vacuolar degeneration of hepatocytes was alleviated.Compared with the PFOA model,the levels of AST,ALT,and 8-OHdG were significantly lower in the LBP-treated group,and the levels of SOD and CAT were significantly increased.In addition,HAT activity was significantly increased after LBP administration,HDAC activity was significantly decreased(P<0.05),and gene expression of fatty acid oxidation-related enzymes was unbalanced.On PND 21,the degree of hepatic steatosis was lower in the PFOA model than at 21 day of age.There was no significant lesion in the LBP-treated group,and the liver index was significantly lower in the 80 and 120 mg/kg LBP groups(P<0.05).There were no significant differences in ALT,AST,CAT,and HAT levels between groups.There was a significant difference between the levels of SOD and 8-OHdG in the PFOA model and the blank group.The activity of HDAC was significantly decreased in the LBP-treated group,and the expression of fatty acid oxidation-related enzymes was significantly regulated.In the LBP treatment trial,60 female mice were randomly divided into 6 groups,10 mice in each group,and were administered on GD 1~17.In the blank control group,0.2 mL of deionized water was administered twice a day.In the PFOA model group,5 mg/kg PFOA solution and 0.2 mL of deionized water were administered per day.In the LPB control group,80 mg/kg LBP solution was administered 0.2 mL of deionized water daily.LPB treatment group was administered with 5 mg/kg PFOA solution,and 40,80 and 120 mg/kg LBP solution were administered respectively.The liver and serum of offspring female mice were collected on PND 21 and 45,and the survival rate and liver index of the offspring were calculated.Levels of AST,ALT,SOD,CAT,8-OHdG,HAT,HDAC,PPAR? and fatty acid oxidation related enzyme were measured on PND 21 and 45,respectively.The results showed that the number of births and survival of 80 mg/kg LBP were significantly higher than that of the PFOA model group on PND 21,and the liver index was significantly decreased(P<0.05).The liver index of the 120 mg/kg LBP group was significantly decreased(P<0.01).HE staining showed that the area of liver necrosis was reduced in the LBP treatment group,and the vacuolar degeneration of hepatocytes was alleviated.Compared with the PFOA model,the levels of AST,ALT,and 8-OHdG were significantly lower in the LBP-treated group,and the levels of SOD and CAT were significantly increased.In addition,HAT activity was significantly increased after LBP administration,HDAC activity was significantly decreased(P<0.05),and gene expression of fatty acid oxidation-related enzymes was unbalanced.At 45 days of age,the degree of hepatic steatosis was lower in the PFOA model than in the 21-day-old group.There was no significant lesion in the LBP-treated group,and the liver index was significantly lower in the 80 and 120 mg/kg LBP groups(P<0.05).There were no significant differences in ALT,AST,CAT,and HAT levels between groups.There was a significant difference between the levels of SOD and 8-OHdG in the PFOA model and the blank group.The activity of HDAC was significantly decreased in the LBP-treated group,and the expression of fatty acid oxidation-related enzymes was significantly regulated.The results showed that LBP can increase the number of births,survival rate,alleviate hepatic steatosis caused by PFOA,reduce liver index,relieve liver oxidative stress,increase histone acetylation level,and not cause damage to normal organisms.