Multi-metabonomics Analysis Of Damp-heat Syndrome In Drug-induced Liver Disease

Drug-induced liver disease(DILI)refers to liver disease induced by various prescription or over-the-counter chemicals,biological agents,traditional Chinese medicines,natural medicines,health products,dietary supplements and their metabolites,and even accessories.With the increase of population,the variety of drugs and the random use of some drugs and food additives in China,the incidence of DILI is increasing year by year.Damp-heat syndrome is one of the most common clinical syndromes of drug-induced liver injury.Therefore,drug-induced liver disease is related to the damp-heat state of the body.In this study,UHPLC-Q-TOFMS technology was used to characterize the metabolites based on the diagnostic factors of damp-heat syndrome of drug-induced liver disease,such as exhaled breath,feces and serum,and the metabolites of exhaled breath,feces and serum were collected to find the differential metabolites between patients with damp-heat syndrome of drug-induced liver disease and normal people,and the three groups of differential metabolites were comprehensively analyzed to explain the scientific connotation of damp-heat syndrome of drug-induced liver disease from a multidimensional perspective.Objective:By comparing the differences of exhaled breath,feces and serum(gasblood-stool)metabolites between patients with damp-heat syndrome of druginduced liver disease and the normal control group,to analyze and find the characteristic differential metabolites and common metabolic pathways,and to form an evidence chain model from a multi-dimensional perspective to explain the scientific connotation of damp-heat syndrome of drug-induced liver disease.Method:Thirty-two patients with damp-heat syndrome of drug-induced liver disease and 36 healthy controls were selected.The exhaled breath,feces and serum metabolites of the subjects were detected by metabonomics.The related data were analyzed by principal component analysis(PCA)and partial least squares(OPLSDA),and the iconic differential metabolites were screened to find the commonness of the differential metabolites.The related metabolic pathways were analyzed by KEGG enrichment,and the correlation analysis of the differential metabolites from different samples was carried out.Results:Among the differential metabolites in fecal metabonomics,there were 65 kinds of differential metabolites with significant changes.There are 102 kinds of differential metabolites that change significantly in the exhaled breath metabolism group;There are 312 kinds of differential metabolites that change significantly in serum metabolic group;The common characteristic differential metabolite of three groups of damp-heat syndrome of drug-induced liver disease is 4-{3-[(3,4dihydroxyphenyl)methyl]-2-methyl butyl} benzone-1,2-diol(NDGA),and the three groups of differential metabolites are enriched into two metabolic pathways:serotonin synaptic pathway and steroid hormone synthesis pathway.Conclusions:In this study,the patients with damp-heat syndrome caused by druginduced liver damage were taken as the research object,and the related diagnostic elements of damp-heat syndrome,such as exhaled breath and foul stool,were objectively characterized by metabolomics,which were associated with the plasma metabolomics that were difficult to observe in the body.The diagnosis principle of TCM was objectively displayed,and the possible metabolic material basis of dampheat syndrome was locked together in the form of evidence chain,thus enhancing the comprehensive evidence of damp-heat syndrome from multiple angles.The results show that the multi-dimensional metabonomics characteristics of damp-heat syndrome in drug-induced liver disease are mainly involved in serotonin synaptic pathway and steroid hormone synthesis pathway.Three groups of differential metabolites and related metabolic pathways together form the evidence chain of damp-heat syndrome,which represents the metabolic characteristics of damp-heat syndrome in drug-induced liver disease.