Dose-dependent cardiotoxic effects of lead following subchronic exposure in an experiment with laboratory animals of different ages
L.V. Shabardina1, V.G. Panov1,2, M.P. Sutunkova1,3, K.M. Nikogosyan1, R.F. Minigalieva1, M.A. Kopenkin1,3
1Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, 30 Popov Str., Yekaterinburg, 620014, Russian Federation
2Institute of Industrial Ecology, Ural Branch of the Russian Academy of Sciences, 20A Sofia Kovalevskaya Str., Yekaterinburg, 620108, Russian Federation
3Ural State Medical University, 3 Repin Str., Yekaterinburg, 620028, Russian Federation
Lead contamination of natural and occupational environments poses a serious health threat, especially during periods of maturation and involutionary changes. Age-related differences in metabolism, detoxification, and reserve capacity may determine different susceptibility to this toxicant, thus necessitating in-depth study.
The aim of this study is to establish dose-dependent effects of lead and compare them between different age groups of experimental animals.
The experiment was conducted on male Wistar rats aged 3 and 12 months. Within each age group, the animals received intraperitoneal injections of lead acetate at doses of 5.5 (1/40 LD50), 11 (1/20 LD50), and 22.88 (1/10 LD50) mg/kg body weight thrice a week for 6 weeks. ECG recordings in leads I and II were performed noninvasively using a tunnel system. Statistical data analysis included multivariate analysis of variance and multiple linear regression. Pairwise intergroup comparisons were performed using the Student’s t-test and Mann – Whitney U test with the Benjamini – Hochberg adjustment (p < 0.05).
The cardiovascular response to lead exposure varied significantly depending on age. In young rats, we observed a linear positive dose – response relationship since the higher dose was associated with longer RR, PQ, QRS, and QT intervals and a lower heart rate. In the adult animals, we established a complex, non-monotonic response: the peak of changes was observed at the minimum dose, and the effect weakened with its increase. Statistical analysis confirmed a significant modulating effect of age on the manifestation of cardiotoxicity.
The limitation of the study is the use of animals of the same sex. Further research is needed to investigate the potential influence of sexual dimorphism on the observed effects.
The age of experimental animals is an important factor modulating the nature and severity of dose-dependent cardiotoxic effects of lead. The findings highlight the necessity of age-specific assessment of cardiac risks in lead-exposed animals and further research into the mechanisms of age-related sensitivity.
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