| Objective:Phe is an essential human amino acid that can be used to synthesize various proteins.It can be metabolized to Tyr by liver and other tissues.Stable Phe metabolic state can maintain the normal growth and development of the body.High phenylalanine may lead to PKU and cause damage to the nervous system.The damage to the nervous system is particularly evident and may lead to mental disorders,mental disabilities,and hypokinesia.At present,there are few studies on liver injury caused by high phenylalanine,whether it is international or domestic.In order to investigate the toxicity mechanism of high phenylalanine on mouse liver and provide the basis for the rational nutrition of Phe's clinical guidance,mice were used as experimental subjects in this paper.By injecting Phe into different groups of C57 mice,we observe it's effects on liver biochemical function and various indexes.Methods:Forty male healthy C57 mice were randomly divided into 4 groups:high dose group: 4.2 mmol/kg,middle dose group: 2.1 mmol/kg,low dose group: 1.05 mmol/kg,control group: distilled water.28 days after intragastric gavage,blood was taken from the eyeball and allowed to stand for 10 min.Serum was separated by cryogenic centrifuge to determine the activity of MAO and P450.The mice were killed by cervical dislocation,and the livers were taken.The antioxidant indexes such as T-SOD,ROS,8-OHd G,MDA,CAT,GSH-Px,and GSH,and Liver enzyme activities such as ALT,AST,LDH,AKP,LAP,GSTA1,Na+-Ka+-ATPase,and Ca2+-Mg2+-ATPase,phospholipid metabolism indicators of PI,PCand PIPT,NO,NOS,TNF-? and HMGB1 hepatotoxicity indicators,LN,HA,Hy P,PIIINP liver collagen metabolism index and the concentrations of Phe and Tyr in blood and liver were measured in the liver tissue homogenates.Results:1.Mouse body weight and liver coefficientAfter 28 days of gavage,none of the mice in each group died,eating and activities were normal,and no abnormal reaction was found.There was no significant difference in body weight between the dose groups(P>0.05).The organ coefficient of the high-dose group was higher than that of the other groups(P<0.05).There was no significant difference between middle-dose and low-dose groups and the control group(P>0.05).2.Concentrations of Phe and Tyr in Mouse Serum and Liver TissuesAfter Phe was intragastric for 28 days,there was no significant difference between the concentration of Phe and Tyr in the serum of each dose group and the control group(P>0.05).The Phe concentration in the liver tissue was significantly higher in the low-dose group than in the control group(P<0.05),and there was no significant difference between the middle-dose and high-dose groups and the control group(P>0.05).Tyr concentrations in the liver tissue were significantly lower in the low-dose and middle-dose groups than in the high-dose and control groups(P<0.05),and there was no significant difference between the high-dose group and the control group(P>0.05).3.Results of mouse liver oxidative damage indexAfter Phe was intragastric for 28 days,the level of ROS in each dose group was significantly lower than that in the control group(P<0.05),while the middle-dose and high-dose groups were higher than the low-dose group(P<0.05).The content of MDA in each dose group was higher than that in the control group(P<0.05);the activity of T-SOD in each dose group was significantly lower than that in the control group(P<0.05),and the T-SOD activity was increased as the dose increased(P<0.05);The GSH content in the low-dose group was significantly lower than that in the control group(P<0.05);the GSH-Px activity was lower in each dose group than in the control group(P<0.05),and the high-dose group was lower than the low-dose group.(P<0.05);The activity of CAT in the high-dose group was significantly lower than that in the control group and other dose groups(P<0.05),and it was significantly higher in the low-dose group than in the control group(P<0.05);The contents of 8-OHd G in the low-dose and high-dose groups were significantly higher than those in the control group(P<0.05).There was no significant difference between the middle-dose group and the control group(P>0.05).4.Measurement results of liver liver cytokine related indicatorsAfter intragastric administration of Phe for 28 days,NO content in each dose group was significantly higher than that in control group(P<0.05),and NO increased with increasing dose(P<0.05);NOS activity of middle-dose and high-dose groups were higher than the control group(P<0.05),there was no significant difference between the low-dose group and the control group(P>0.05);the content of TNF-? in the middle dose and high dose group was significantly higher than that in the low dose and high purity water group(P<0.05),and there was no significant difference between the low dose group and high purity water group(P>0.05),The content of HMGB1 in the low-dose and high-dose groups was significantly higher than that in the medium-dose and high-pure water group(P<0.05),and the middle-dose group was lower than the high-pure water group(P<0.05).5.Changes of Liver Tissue Enzyme Activity in MiceAfter 28 days of Phe gavage,the ALT vitality of each dose group was significantly lower than that of the control group(P<0.05).There was no significant difference between the middle-dose group and the low-dose group and the high-dose group respectively(P<0.05);AST vitality of each dose group was significantly lower than the control group(P <0.05),and AST decreased as the dose increased(P <0.05);GSTA1 vitality of each dose group was significantly lower than control group(P <0.05).There was no significant difference between the low-dose group and the middle-dose group and the high-dose group(P>0.05).The activity of AKP in the middle-dose group was significantly lower than that in the control group(P<0.05).There was no significant difference between the high-dose group and the low-dose and control group(P>0.05).The activity of the LDH in low-dose and middle-dose groups were significantly lower than the control group(P<0.05),and there was no significant difference between the high-dose group and the control group(P>0.05);the activity of the LAP in high-dose group was lower than other groups.There was no significant difference between middle-dose and low-dose group and control group(P>0.05);The activity of Ca2+-Mg2+-ATP in the high-dose group was lower than that in the other groups(P<0.05).There was no statistical difference between the middle-dose and low-dose groups and the control group(P>0.05);The vitality of Na+-K+-ATP was significantly lower in each dose group than in the control group(P<0.05).There was no significant difference between the high-dose group and the low-dose and middle-dose groups(P>0.05);The vitality of MAO in middle-dose and high-dose groups was higher than the low-dose and control group(P<0.05),there was no statistical difference between the low-dose group and the control group(P>0.05);the activity of P450 in high-dose group was lower than the other groups(P<0.05).There was no statistical difference between the middle-dose and low-dose groups and the control group(P>0.05).6.The index results of phospholipid metabolism in mouse liver membraneAfter Phe was intragastric for 28 days,the content of PC in each dose group was significantly lower than that in control group(P<0.05).There was no significant difference between middle-dose group and high-dose group(P>0.05).The content of PI in high-dose group was higher than other groups(P<0.05),there was no significant difference between the low-dose group and the control group(P>0.05);the PIPT content in middle-dose and the high-dose group was higher than low-dose and control group(P<0.05).There was no significant difference between the low-dose group and control group(P>0.05).7.Measurement of collagen metabolism index in liver tissue of miceAfter Phe was intragastric for 28 days,the content of HA was significantly higher in each dose group than in the control group(P<0.05).The high-dose group was higher than the middle-dose and low-dose groups(P<0.05);The content of PIIINP in high-dose group was higher than other groups(P<0.05),there was no significant difference between the low-dose group and the control group(P>0.05);the LN content in the high-dose group was higher than low-dose and control groups.There was no significant difference between middle-dose,low-dose group and control group(P>0.05);the content of Hyp was higher in the high-dose group than in the other groups(P<0.05).There was no significant difference between the middle-dose and low-dose group and the control group(P>0.05).Conclusion:Continuous gavage of Phe in mice can cause lipid peroxidation of liver tissues;produce hepatotoxicity,release cytokines;lead to disorder of liver enzyme activity;interfere with liver cell membrane phospholipid metabolism;affect liver protein collagen metabolism. |
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