Metabolomic study of animal blood after subchronic and chronic inhalation exposure to lead oxide nanoparticles

Introduction. High emissions from various technological processes and the increasing practical use of lead oxide nanoparticles (NPs PbO) make it relevant to assess their toxicity. The use of non-targeted blood metabolomics methods to study the effects of NPs PbO on mammalian organisms has not previously been described in the literature.

The purpose of this work. To apply metabolomic analysis to study the subchronic and chronic inhaled effects of NPs PbO on laboratory animals.

Materials and methods. The experiment was conducted on fifty female rats randomly divided into equal groups. Some of the animals were exposed to inhaled NPs PbO for 2 months: experimental group and control. Another part of the animals was exposed to inhaled NPs PbO for 8 months: the experimental group and the control. The concentration of NPs PbO in the respiration zone of the animals was 0.215 mg/m³. A semi-quantitative metabolomic blood test was performed using liquid chromatography-mass spectrometry.

Results. According to the results of a metabolomic analysis of animal blood after 2 months of exposure, a decrease in the content of 5 LPC, 3 LPE and an increase in the content of 1 LPC were detected. At the same time, exposure to NPs PbO in the same concentration for 8 months was shown to cause an increase in the content of 5 LPC, 4 acylcarnitines, 2 polyunsaturated fatty acids, as well as a decrease in 1 LPC. The constructed ROC curves for the combination of the detected metabolites had an AUC = 0.975 for subchronic exposure and AUC = 0.948 for chronic exposure.

Limitations. The study was conducted using female Wistar rats with no potential sex differences taken into account.

Conclusion. Metabolic changes in the blood after inhaled exposure to NPs PbO at a concentration of 0.215 mg/m³ are characterized by a multidirectional violation of lipid metabolism at different periods, probably indicating autophagy after subchronic exposure and apoptosis after chronic exposure.

Compliance with ethical standards. Ethics approval was provided by the institutional Ethics Committee of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers (protocol No. 4 of July 12, 2022).

Contribution:
Unesikhina M.S. — data collection and processing, draft manuscript preparation, editing;
Minigalieva I.A. — study conception and design, editing;
Kikot A.M. — editing;
Sutunkova M.P. — study conception and design, editing.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

Conflict of interest. The authors declare no conflict of interest.

Funding. The study had no sponsorship.

Received: February 10, 2025 / Revised: June 18, 2025 / Accepted: June 26, 2025 / Published: September 25, 2025

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