Plasma metabonomic study on the changes of dibutyl phthalate using ~1H NMR / 中国职业医学

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.