Application Of Metabolomics Technology To Analyze Rat Plasma Metabolic Profile Changes With Time After Administrated Mecathinone

Objective:The metabolomics technique was used to study the time-dependent changes of plasma metabolic profile of rats after intraperitoneal injection of mecathinone.In order to screen the biomarkers raleted to mecathinone injection and time of administration,and to explain its toxicological mechanism at the metobolic level.Methods:20 male SD rats were randomly divided into two groups.The blood samples were collected from internal canthal venous plexus at 3min,35 min and 3h after injection of mecathinone,respectively.The metabolites in plasma were detected by ultra-high performance liquid chromatography-time-of-flight mass spectrometry(UPLC-TOF-MS).Data pattern recognition is based through principal component analysis(PCA),partial least squares-discriminant analysis(PLS-DA)and orthogonal partial least squares-discriminant analysis(OPLS-DA).Combined with the ranking value of variable importance in the projection(VIP)and one-way ANOVA analysis to screen the potential differential metabolites in plasma of rats injected intraperitoneally with mecathinone and explain the toxicological mechanism.Results:There was a significant difference in plasma metabolic profile between the rats injected intraperitoneally with methcathinone and the blank control group.Nine characteristic differential metabolites that related to drug time were screened from the experimental group,which were 1,7-Dimethylxanthine,1-Methyladenosine,cis-9-Palmitoleic acid,3-Hydroxydodecanoic acid,Theophylline,Arachidic acid,Erucic acid,Nervonic acid,Glycerophosphocholine.Betaine and linoleic acid are characteristic differential metabolites of 3min after intraperitoneal injection of mecathinone.Creatine,1-Methylnicotinamide,L-Anserine,S-Methyl-5’-thioadenosine,Cortexolone,L-Alanine,2-Hydroxy-3-methylbutyric acid,L-Carnosine,Thymidine,L-Isoleucineare are the characteristic differential metabolites of 35 min after intraperitoneal injection of mecathinone.L-Palmitoylcarnitine,4-Guanidinobutyric acid,D-Proline,Oxindole,L-Citrulline,L-Glutamate,Indoxyl sulfate,Pantothenate and Taurine are the characteristics of 3 hours after intraperitoneal injection of mecathinone.D-Mannose produces hippuric acid under the action of benzoyl-Co A.Hippuric acid can produce pyrrolidone under the action of a series of enzymes,and then metabolize to produce cathinone,ephedrine and pseudoephedrine,while cathinone,ephedrine and pseudoephedrine are all metabolites of methcathinone.Therefore,D-mannose and hippuric acid may be used as biomarkers of methcathinone into the body.The metabolic pathways involved in the above differential metabolites are mainly caffeine metabolism,amino acid biosynthesis and metabolism,fatty acid metabolism and other metabolic pathways,which are related to energy metabolism and protein catabolism.Conclusion:In this experiment,the time-related characteristic differential metabolites were found from the metabolomics technology,and the affected metabolic pathways were found after the metabolic pathway analysis and functional enrichment of the differential metabolites,which can explain the clinical manifestations and toxicological machanism after the use of mecathinone from the metabolic level.The results of this study can provide a scientific basis for characterization of drug abuse and the inference of the time of drug abuse in suspected cases of mecathinone taking drugs.