Investigation of changes in rat’s blood metabolomic profile, caused by lead exposure

Abstract

Introduction. The prevalence of lead in the environment, due to human production and economic activities, and the xenobiotic nature of the element substantiate the relevance of studying the changes caused by the action of this metal. Materials and methods. A non-target metabolomic screening of the blood of rats exposed to intraperitoneal administration of lead acetate by HPLC-mass spectrometry was carried out. The expression of the selected masses was compared with those for the control group of animals. The masses that significantly changed the intensity compared to the control were subjected to fragmentation to obtain characteristic fragments. The annotation of metabolites was performed by searching in MS/MS databases and by comparison with in silico fragmentation spectra. The involvement of annotated metabolites in metabolic processes was established by literature analyzing. Results. Non-target metabolomic screening revealed 37 m/z values for the exposed group, significantly changing the intensity compared to the control. Annotation using fragmentation spectra and in silico fragmentation allows establishing the structure of eight metabolites, including an epoxy derivative of linolic acid, 15-hydroxyeicosatetraenoic acid, four oxo- and hydroxyacylcarnitine derivatives of long-chain fatty acids, one acylcarnitine derivatives of medium-chain fatty acids and one lysophosphoserine. Conclusion. Analyzing the literature, the known functions of the identified metabolites were established and attributed to the known metabolic processes. So, oxo- and hydroxyacylcarnitines are derivatives for intermediate products of β-oxidation fatty acids - it is increased concentration compared to the control indicates a violation of this process under the influence of oxidative stress caused by lead. Epoxy and 15-hydroxy derivatives of fatty acids (increased content relative to the control group) act as regulatory metabolites (vasodynamic activity), on the one hand, and markers of lead-induced hypoxia on the other hand. The increase of the concentration for the lysophosphatidylserine derivative indicates the intensification of apoptotic processes in the organism of the exposed group in contrast to the control.