Alterations in the expression of genes involved in the mitochondrial apoptotic pathway upon exposure to lead oxide nanoparticles

Introduction. Lead production technologies pollute the air with aerosol nanoparticles, including those of lead oxide (PbO NPs). Lead can cause oxidative stress that leads to cell death. Experimental studies of effects of PbO NPs at the gene transcription level will expand our knowledge of the mechanisms of PbO NP toxicity and improve assessment of health risks for the population exposed to them.

The purpose was to study the expression of genes involved in antioxidant protection and apoptosis following subchronic inhalation exposure of lead nanoparticles to rats.

Materials and methods. Female albino rats were exposed to PbO NPs in an inhalation chamber at a concentration of 1.55 ± 0.06 mg/m³, 4 hours a day, 5 days a week for 1 month; the control group breathed clean air in a similar chamber. After exposure cessation, RNA was isolated from fragments of the olfactory bulb, cerebellum, lung, and liver. Expression of the P53, BAX, BCL-2, GSTM1, GSTP1, and SOD2 genes was determined by quantitative real-time PCR. The data was analyzed using the Mann-Whitney test.

Results. In the olfactory bulb, BCL-2 gene expression was significantly lower, while that of P53 was higher in the exposed rodents compared to the controls. In the cerebellum of the exposed animals, BAX and P53 genes expression was statistically higher and lower than in the control group, respectively. BCL-2 gene expression in the liver was significantly lower in the exposed group.

Limitations. The experiment involved only female rats, so it does not take into account sex differences and considers only gene expression, neglecting post-translational mechanisms and protein expression.

Conclusion. Inhalation exposure to PbO NPs at the concentration of 1.55 ± 0.06 mg/m³ causes changes in the expression of genes associated with mitochondrial apoptosis in the brain and liver, but not in the lungs of laboratory rats.

Compliance with ethical standards. The local Ethics Committee of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers concluded the animals were kept, fed, cared for, and sacrificed in accordance with generally accepted requirements, taking into account the ARRIVE guidelines. Ethics approval was provided by the local Ethics Committee of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers (protocol No. 4 of July 12, 2022).

Contribution:
Kikot A.M. – data collection and processing, statistical analysis, draft manuscript preparation, editing;
Shaikhova D.R. – data collection and processing, draft manuscript preparation, editing;
Bereza I.A. – data collection and processing, draft manuscript preparation, editing;
Minigalieva I.A., Sutunkova M.P. – study conception and design, editing;
Nikogosyan K.M. – data collection, 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.

Acknowledgement. The study had no sponsorship.

Received: October 18, 2024 / Accepted: November 19, 2024 / Published: December 17, 2024