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Study On The Protective Effect Of Compound Glycyrrhizin On Liver Injury And Its Acute Toxicity And Injection Irritation

Posted on:2022-10-05Degree:MasterType:Thesis
Country:ChinaCandidate:N MaoFull Text:PDF
GTID:2543307133984929Subject:Veterinary Medicine
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Liver is the main place of substance metabolism in animals,and liver damage will affect the normal operation of various functions of the body.Licorice was first published in"Shen Nong’s Materia Medica".It is sweet in nature,calm in taste,nourishes the spleen and qi,relieves emergency and detoxification,and harmonizes a hundred medicines.It is one of the most commonly used Chinese medicines in traditional Chinese medicine prescriptions.Modern pharmacological studies have shown that glycyrrhizic acid,the active component of glycyrrhizin,can protect liver cell membranes,improve liver function,promote liver cell repair and so on.The compound glycyrrhizin is mainly composed of ammonium glycyrrhizinate,which has a variety of pharmacological effects such as anti-inflammatory,anti-oxidation and immune regulation,and is widely used in medicine for the prevention and treatment of various liver diseases.In this paper,in order to introduce glycyrrhizin related preparations into the pet clinic,the related basic research on compound glycyrrhizin was carried out,including:using paracetamol-induced liver injury model in mice,evaluating the liver-protecting effect of compound glycyrrhizin and screening the best liver-protecting dose;evaluating the acute toxicity of compound glycyrrhizin through oral and intraperitoneal injection;using left and right self-control method to investigate the local irritation of compound glycyrrhizin on rabbit muscle and subcutaneous injection.1 Study on the protective effect of compound glycyrrhizin on liver injury in miceEstablishment of acetaminophen induced liver injury model in mice:clean ICR male mice were selected to establish the model by intraperitoneal injection of acetaminophen.First,300,400 and 500 mg/kg groups were used to screen the damage dose,then 300,350and 400 mg/kg groups were set to optimize the damage dose,and finally three parallel damage groups were set to confirm the dose.Results:the mice in 500 mg/kg group were dead and abandoned.The optimal dose test showed that the serum ALT and AST levels of mice at 350 mg/kg dose were significantly increased,and hepatocyte injury was more common,which was the optimal dose.In the dose confirmation test,the mental state of the mice in the three 350 mg/kg parallel groups was the same,the serum ALT and AST levels had no significant difference,but were significantly higher than those in the blank group,and the hepatocytes were damaged,swollen and denatured,and the degree of damage had no significant difference.Conclusion:the optimal dose of acetaminophen for liver injury in mice is 350 mg/kg.Protective effect of Compound Glycyrrhizin on liver injury in mice:blank group,liver injury model group and compound glycyrrhizin protection group were set up.The mice in the protection group were given compound glycyrrhizin at the doses of 7.5,11.25,22.5,45and 60 mg/kg(glycyrrhizin),twice a day for 7 days.The mice were weighed before administration and 24 hours after drug withdrawal,and blood samples were collected 24hours after drug withdrawal to detect serum indexes.The liver index was calculated and the histopathological changes were observed.Results:compared with the model group,the serum TP,ALB levels and weight gain rate of mice in Compound Glycyrrhizin 22.5,45 and60 mg/kg dose groups were significantly increased(P<0.05),the serum ALT,AST levels and liver index were significantly decreased(P<0.05),and there was no significant difference among the three protective dose groups.Conclusion:Compound Glycyrrhizin can effectively reduce enzyme activity,promote protein synthesis,reduce cell damage,and has better liver protection effect.The optimal oral dosage is 22.5 mg/kg.2 Study on acute toxicity of compound glycyrrhizinAcute toxicity test of oral administration:in the pre-test,there were 5 different dose administration groups and one normal saline negative control group,with 4 SPF mice in each group,half male and half female.In the treatment group,5000,4000,3000,2000,and1000 mg/kg(by weight of the preparation)of the test solution were orally administered by gavage within 24 hours.In the formal test,the number of mice was increased to 10,half male and half female.The mice were administered by gavage once every 2 hours,and the cumulative dose was 5000 mg/kg within 24 hours.The test was repeated twice.After 7 days of observation,there was no death,normal behavior,dietary activity,and no toxic reaction.Results the oral LD50of compound glycyrrhizin tablets was more than 5000 mg/kg,which was a non-toxic substance.Acute toxicity test of injection:in the pre-test,there were 4 different dose groups and one normal saline negative control group,4 SPF mice in each group,half male and half female.In the treatment group,compound glycyrrhizin injection was injected intraperitoneally at the doses of 140,80,40 and 20 m L/kg within 24 hours.In the formal test,the number of mice was increased to 10,half male and half female.Compound glycyrrhizin injection was injected intraperitoneally once every 2 hours,and the cumulative dose was 140 m L/kg within 24 hours.The test was repeated twice.The observation indexes were the same as oral administration.Results the cumulative dose of Compound Glycyrrhizin Injection reached 140 m L/kg within 24 hours,and no mice died,indicating that the drug had no obvious acute toxicity.3 Study on injection irritation of compound glycyrrhizinMuscle irritation and subcutaneous irritation tests were conducted in healthy rabbits.Compound glycyrrhizin injection was subcutaneously injected into left quadriceps femoris or lateral chest wall of rabbits,0.5 m L/kg,Once a day for 7 days,equal volume of normal saline was injected on the right side as negative control.The clinical manifestation and skin condition of injection site were observed and recorded every day.The rabbits were euthanized 72 hours after discontinuation of the drug and dissected to observe the local irritation of the injection site for scoring and grading,and the injection site tissues were taken for histopathological examination.Conclusion:Compound glycyrrhizin injection was not significantly irritating to both muscle and subcutaneous tissues of rabbits.
Keywords/Search Tags:compound glycyrrhizin, liver injury, acute toxicity, irritating
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