Human lung alveolar cells exposed to cigarette smoke: role of 3,5-diiodothyronine in mitochondrial dysfunction

<bold>Background:</bold> Cigarette smoke (CS) is a socially acceptable addiction and a major risk factor for chronic lung conditions. Oxidative stress and mitochondrial dysfunction are thought to play an important role in CS-induced pulmonary injury. 3,5-diiodothyronine (T2) affects energy metabolism, having mitochondria as a major target. However, T2 has been relatively understudied in relation to lung diseases. <bold>Aims:</bold> to investigate T2 ability to mitigate CS-mitochondrial dysfunction in an in vitro model of human epithelial alveolar cells. <bold>Methods:</bold> ATP synthesis, as a marker of mitochondrial activity, was assessed in A549 cells exposed to CS using a bioluminescence assay. Evaluation of oxidative status was conducted through examination of superoxide radical production, H2O2 levels, and Mito-Tracker Green (MTG) FACS measurements. Moreover, we are currently evaluating superoxide dismutase (SOD) activity and cytochrome c oxidase (COX) capacity using an Oroboros O2k-FluoRespirometer. <bold>Results:</bold> CS significantly affected ATP production while pretreatment for 2h with 10μM T2 mitigates these effects (p <0.01). Additionally, T2 reduced the levels of superoxide and H2O2 induced by CS exposure (p <0.05). Finally, MTG labelling correlated with CS-induced redox imbalance (p <0.0001), whereas T2 pretreatment showed restoring properties (p <0.05). <bold>Conclusions:</bold> Our results provide new insights into the protective effects of T2 against CS-induced mitochondrial damage. Ongoing evaluations of the correlation between CS and SOD/ COX activity could pave the way for future studies focused on T2 as a novel promising strategy for CS-related diseases.