NMR-based Metabonomics Study Of The Toxicity Of Dibutyl Phthalate

Dibutyl phthalate(DBP)has been widely used as a plasticizer in various fields,but its potential toxicity is also concerned to the public.This study is based on the theory of molecular biology and biochemistry,using metabolomics methods of nuclear magnetic resonance(NMR),and combined with traditional toxicological methods,histopathological examination and plasma biochemical analysis.To study the dynamic changes of endogenous metabolites in the biological fluid after rats treated with DBP,to explain the relationship between the metabolic response and the internal tissue damage produced in the body,and then elaborate the toxic mechanism of DBP.Metabolomics and pattern recognition analysis showed that the changes of endogenous metabolites were significantly different from those in the control group in the body fluids of rats after rats treated with DBP.Analysis of plasma biochemical indicators showed liver and kidney dysfunction,histopathological examination also showed that the testis,liver and kidney tissue damage.And the results showed uniformity between plasma biochemical analysis,histopathological examination and the difference in the metabolites.The results showed that the metabonome of rats induced with DBP differed obviously from the control group.Compared with the control group,the endogenous metabolites variation including:(1)plasma from rats induced with DBP had higher levels of lactate and pyruvate,and lower levels of lipid protein,?-hydroxybutyrate,glycoprotein,citrate,glucose,creatine phosphate,unsaturated fatty acids,tyrosine and phenylalanine.(2)urine from rats induced with DBP had higher levels of leucine,isoleucine,valine,?-hydroxybutyric acid,alanine,lysine,acetate,hippurate and tryptophan,and lower levels of lactate,glycoprotein,methionine,acetone,?-ketoglutarate,glutamine,citrate,malonate,choline,TMAO,taurine,creatine,creatinine,glucose,aconitic acid,isocitrate,malic acid and formate.(3)feces from rats induced with DBP had higher levels of leucine,isoleucine,tryptophan,valine,alanine,acetate,lysine and adenine,and lower levels of lactate,glycoprotein,methionine,alpha-ketoglutarate,glutamine,malonate,choline,trimethylamine,taurine,creatine,beta-glucose,malic acid and formate.Moreover,the differences in the metabolites induced by DBP are dose-dependent and time-dependent.Based on the theory of hygienic toxicology,histopathology and biochemistry,it is concluded that the change of metabolites can be related to the disorder of some metabolic pathways induced by DBP.Including tricarboxylic acid cycle,carbohydrate metabolism,protein metabolism and lipid metabolism,and also indicate the presence of intestinal bacteria in the body of the imbalance.The disruption of these biochemical metabolic pathways and the toxicity of DBP was a certain degree of correlation.In this study,we can monitor the whole process of DBP toxicity comprehensively,and explain the mechanism of toxic effects caused by DBP from the whole level,and provide new ideas for toxicological research of environmental chemical substances.