The effect of MXF-19 on T-regulatory Lymphocytes of Rats Under Conditions of Aseptic Inflammation Caused by Metal-Induced Immunodepression

نویسندگان

1 Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan

2 Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan

3 Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan

4 Murdoch University Health Futures Institute, Perth, Australia

5 Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan

6 Laboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences, Almaty, Kazakhstan

7 Laboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences, Almaty, Kazakhstan

doi
10.26655/JMCHEMSCI.2025.5.6
چکیده

Heavy metals such as cadmium (Cd) and lead (Pb) are toxicants that negatively impact the immune system, enhancing systemic inflammation and disrupting the balance between pro-inflammatory and regulatory processes. They contribute to the reduction of CD4+ T-lymphocytes and regulatory T-cells (Treg), which is associated with an increased risk of chronic inflammation and autoimmune disorders. These effects arise from heavy metals' ability to disrupt proliferation and induce apoptosis of immune cells, as well as alter the expression of key regulatory markers such as FoxP3. In this regard, the aim of the present study was to investigate the effects of Cd and Pb on the course of aseptic inflammation (SI), as well as the possibility of immune modulation of identified disorders. The study was conducted on 5 groups of animals, with 90 outbred male rats weighing 180-220±20g, kept under standard vivarium conditions on a regular diet. In experimental animals, intoxication was induced by administering Cd and Pb at a dose of 2.5 mg/kg body weight orally for two weeks, after which aseptic inflammation was modeled in the animals. In this work, the activity of CD4+, CD4+CD25+ (activated T-cells) and CD4+FoxP3+ was studied using flow cytometry. This study aimed to compare the effectiveness of two synthesized compounds — Complex and MHF-19 — for correcting disorders caused by the combined effects of Cd and Pb. The obtained results show that both compounds promote the restoration of CD4+, CD4+CD25+ and CD4+FoxP3+ cell populations; however, their mechanisms of action differ significantly. Complex provides rapid suppression of inflammatory response and restoration of T-cell populations, which is consistent with previous data on its universal immunomodulatory action. Meanwhile, MHF-19 exhibited a more pronounced and sustained effect on Treg, manifesting as in an increase in the proportion of CD4+FoxP3+ cells and restoration of immune homeostasis with long-term use. Thus, MHF-19 demonstrated advantages in correcting chronic inflammation, especially in cases of regulatory mechanism disorders. The results underscore the promise of using MHF-19 for correcting inflammatory conditions caused by toxic effects of heavy metals and for managing chronic inflammatory processes.