Sex-related differences in inhibition of SDH activity of rat blood lymphocytes exposed to lead acetate

Introduction. Long-term health risks increase due to occupational and environmental exposure to lead compounds, one of the main targets of which is the mitochondria at the subcellular level. Lead inhibits the activity of energy metabolism enzymes, including succinate dehydrogenase (SDH). Currently, the data on sex-related physiological and metabolic differences that may influence these toxic effects are limited.

The aim of the study was to experimentally determine the nature of the effect of lead acetate on SDH activity in peripheral blood lymphocytes of rats, depending on sex.

Material and methods. The experiment was performed on outbred male and female rats (3–4 months old, body weight 220 ± 20 g). The animals were divided into 4 groups (n = 10): “Lead ♀” and “Lead ♂” received lead acetate with water (819 mg/l) for 45 days, “Control ♀” and “Control ♂” received drinking water. After exposure, the area of formazan levels was determined in blood smears using BloodRunner and BioImagine software to assess SDH activity, for which the samples were incubated in appropriate solutions containing oxidized nitrosinium tetrazolium and SDH substrate succinate. Statistical processing was performed using Python (version 3.11), SciPy (version 1.11.1) and statsmodels (0.14.0) libraries. In the two-factor assay, rank analysis of variance was applied, and the Mann–Whitney U-test with the Bonferroni correction (p < 0.05) was used for pairwise comparisons.

Results. Statistically significant effects of the factors “lead” and “sex” and their interaction were revealed. In lead-exposed females the activity of SDH did not change compared to the control (p = 0.270), while in lead-exposed males the activity of SDH significantly decreased (p < 0.001). The difference between the groups “Lead ♀” and “Lead ♂” also had high significance (p < 0.001).

Limitations. Only one parameter, SDH activity, was evaluated. In this study, we limited ourselves to assessing the total SDH activity, as preliminary experiments showed that the contribution of endogenous succinate was insignificant in our conditions and did not affect the comparative results of the groups.

Conclusion. Lead acetate inhibits SDH in blood lymphocytes in a sex-specific manner: male rats are more sensitive than female rats. It is necessary to take sex into account when assessing the health risks associated with lead contamination.

Compliance with ethical standards. The experiment was approved by the Local Ethics Committee of the Yekaterinburg Medical and Scientific Center for Prevention and Health Protection of Industrial Workers, Rospotrebnadzor (Protocol No. 1A dated 03.02.2025) in accordance with the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (ETS N 123), and Directive 2010/63/EC of the European Parliament and of the Council of 22 September 2010 on the Protection of Animals Used for Scientific Purposes.

Authors’ contribution. All co-authors made an equal contribution to the research and preparation of the article for publication, and all co-authors are responsible for approving the final version of the article and ensuring the integrity of all its parts.

Conflict of interests. The authors declare that there are no obvious and potential conflicts of interest in connection with the publication of this article.

Funding. The study had no sponsorship.

Received: March 6, 2026 / Accepted: June 1, 2026 / Published: June 30, 2026

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