Blood metabolic fingerprinting of rats, subjected to subchronic lead exposure

Abstract

Introduction Environmental pollution with heavy metals is vital issue in the present time. Lead, as one of the environmental contaminators, deserves attention due to its applicability in human activity and its xenobiotic character. Methods In this study we used an untargeted metabolomic approach – the metabolomic fingerprinting method. Lead acetate was intraperitoneally injected to rats within the framework of a subchronical experiment and blood samples were analyzed by UHPLC-MS. Metabolite expression was qualitatively compared between treated and control groups. For substances with a significant content difference, tandem CID spectra for structure elucidation were obtained using an exact mass search by generating a list of potential formulas, by a characteristic fragments database search, using in silico mass spectra prediction, and by looking for a specific fragmentation rearrangement. Results Untargeted metabolomic analysis shows 37 metabolites with significant changes in expression in comparing the control and exposure group. Annotation by the fragment spectra analysis was carried out for 8 metabolites. These include epoxy-derivative of linoleic acid, hydroxy- and oxoacylcarnitines of long-chain fatty acids, 15-hydroxyeicosatetraenoic acid, acylcarnitine of middle-chain fatty acid and lysophosphatidylserine derivative. Conclusions Literature analysis allows to establish known functions of annotated metabolites. Connections to manifestations of lead poisoning were established. Specifically, hydroxy- and oxoacylcarnitines are intermediates in the beta-oxidation process of fatty acids – increased concentration of these derivatives may be a sign of disturbances in this process under the influence of lead-induced oxidative stress. Epoxy- and hydroxyderivatives of polyunsaturated fatty acids, which demonstrate elevated concentration levels possess regulatory activity (vasodynamic, antiapoptotic, and antioxidative action) on the one hand, and presumably are biomarkers of oxidative stress. Elevated levels of lysophosphatidylserine may be evidence of apoptotic process intensification.

Keywords

• lead exposure
• rat metabolomic
• metabolic fingerprinting
• blood metabolomic
• lc-ms metabolomic
• tandem mass-spectrometry