Metformin modulates oxidative stress via activation of AMPK/NF-κB signaling in Trisomy 21 fibroblasts: an in vitro study
Abstract
Introduction Oxidative stress and impaired antioxidant defenses are key contributors to cellular dysfunction in Trisomy 21 (T21), highlighting the need for targeted therapeutic strategies. This study explores the modulatory effects of metformin on oxidative stress and antioxidant capacity in T21. Methods An in vitro model was employed using human fibroblast cells with T21 (CCL-54 – Detroit 532 and Detroit 539 – CCL-84; ATCC) alongside normal fibroblasts as a control group (PCS-201-012; ATCC). These cells were treated with varying doses of metformin (10 μM, 30 μM, and 50 μM) for 48 h to assess its pleiotropic protective effects and their impact on oxidative-metabolic cellular profiles. Results Our results demonstrate that metformin treatment significantly reduced total oxidative capacity (TOC) and levels of oxidative DNA/RNA damage products in T21 cell lines (CCL-84 and CCL-54). Additionally, metformin markedly increased total antioxidant capacity (TAC) in these fibroblasts. Furthermore, metformin influenced key signaling pathways, as evidenced by increased levels of nuclear factor kappa B (NF-κB) and enhanced activity of protein kinase AMP-activated alpha 1 (PRKAA1) and AMP-activated protein kinase (AMPK) in T21 cell lines. Conclusions These findings highlight metformin’s significant role in modulating oxidative stress and inflammation- related mechanisms in T21. Given the growing interest in managing oxidative stress during pregnancies affected by T21, this study presents…
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