Toxic Effects of Heavy Metals on the Immune System and New Approaches to Restoring Homeostasis
نویسندگان
1 Asfendiyarov Kazakh National Medical University, Department of Pathological Physiology named after Professor A.N. Nurmukhambetov, Almaty, Kazakhstan
2 Lithuanian University of Health Sciences, Lithuania, Kaunas
3 Asfendiyarov Kazakh National Medical University, Department of Pathological Physiology named after Professor A.N. Nurmukhambetov, Almaty, Kazakhstan
4 Asfendiyarov Kazakh National Medical University, Department of Pathological Physiology named after Professor A.N. Nurmukhambetov, Almaty, Kazakhstan
5 Asfendiyarov Kazakh National Medical University, Department of Pathological Physiology named after Professor A.N. Nurmukhambetov, Almaty, Kazakhstan
6 Murdoch University Health Futures Institute, Perth, Australia
7 A.B. Bekturov Institute of Chemical Sciences, Almaty, Kazakhstan
8 A.B. Bekturov Institute of Chemical Sciences, Almaty, Kazakhstan
doi
10.26655/JMCHEMSCI.2024.11.1چکیده
Heavy metals such as cadmium and lead have profound effects on the immune system, causing both overstimulation and suppression of immune responses. This dysregulation leads to immune dysfunction and increases the risk of adverse inflammatory outcomes. Disruption of immune regulation can result in chronic inflammation, requiring a detailed understanding to develop effective therapeutic strategies. The aim of the present study was to investigate the effects of cadmium chloride (CdСl2) and lead acetate (Pb(CH3COO)2) on the course of aseptic inflammation (SI), as well as the possibility of immune modulation of the identified disorders. The study was conducted on 4 groups of animals, with 42 outbred male rats weighing 180-220 g (±20 g), kept under standard vivarium conditions on a regular diet. Experimental animals were intoxicated with 2.5 mg/kg doses of Cd and Pb orally for two weeks, after which aseptic inflammation was modeled in the animals. In this work, we investigated the activity of CD4+, CD4+CD25+ (activated T cells), CD4+FoxP3+, CD4+FoxP3+CTLA-4+, CD45R(B220), RT1+ from the CD45+CD45R(B220) + population using flow cytometry; IL-6, TGFβ using enzyme-linked immunosorbent assay (ELISA); and hematological blood analysis. It was found that cadmium and lead salts cause immune system dysfunction, leading to dysregulation of inflammation and increasing the risk of adverse outcomes. Treatment with Complex demonstrated potential in restoring the balance of effector and regulatory lymphocytes. Complex, after 7 days, through activation of IL-6 and TGF-β, restored splenic CD4+ lymphocyte populations, selectively stimulated FoxP3+ expression, but did not affect the suppressive activity of CTLA-4+. Complex also activated innate and adaptive immunity, enhancing the antigen-presenting activity of macrophages and stimulating leukocyte reactions, which is especially important for a favorable outcome of the inflammatory process against the background of heavy metal intoxication.
