ABSTRACT
OBJECTIVE: To screen small molecule metabolites of dibutyl phthalate( DBP) in the rat plasma using ~1H nuclear magnetic resonance( NMR) technology; and to clarify the changes of metabolites and possible mechanism in metabolic regulation of DBP in rats from the molecular level and the aspects of material and energy metabolism. METHODS: According to random number table method,twenty-four specific pathogen free SD male rats were divided into four groups: control group,low dose group,middle dose group and high dose group with the given dose of 0,500,1 000 and1 500 mg / kg of body mass,respectively. After giving DBP of gavage once a day for two weeks,the plasma samples were obtained,and ~1H NMR spectra was recorded. The plasma metabonomic profiles were analyzed using pattern recognition.Difference metabolites were screened by principal components analysis,partial least squares-discriminate analysis and orthogonal partial least squares-discriminate analysis. Biomarkers was screened by variable importance in the projection norm. RESULTS: There were changes of twelve important metabolites in the plasma metabonomic profiles between DBP treatment groups and control group. The differences of metabolites had dose-effect relationship. Plasma levels of high density lipoprotein cholesterol, low density lipoprotein cholesterol, hydrobutyrate, glycoprotein, citric acid, glucose,creatine phosphate,unsaturated fatty acid,tyrosine and phenylalanine were reduced( P < 0. 05),while lactic acid and pyruvic acid were increased( P < 0. 05). CONCLUSION: DBP induces the metabolic disorders including amino acid metabolism,lipid metabolism and energy metabolism.