Protective Action of 3,5-Diiodo-L-Thyronine on Cigarette Smoke-Induced Mitochondrial Dysfunction in Human Alveolar Epithelial Cells
<b>Background</b>: Cigarette smoke (CS) is a major risk factor for chronic lung conditions. Oxidative stress and mitochondrial dysfunction play a crucial role in CS-induced pulmonary injury. 3,5-Diiodothyronine (T2) affects energy metabolism, having mitochondria as a major target. Howeve...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-04-01
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| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/13/5/1014 |
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| Summary: | <b>Background</b>: Cigarette smoke (CS) is a major risk factor for chronic lung conditions. Oxidative stress and mitochondrial dysfunction play a crucial role in CS-induced pulmonary injury. 3,5-Diiodothyronine (T2) affects energy metabolism, having mitochondria as a major target. However, the underlying mechanisms of T2 related to lung diseases are poorly understood. <b>Aims</b>: To investigate the protective action of T2 on CS-induced mitochondrial dysfunction in an in vitro model of human epithelial alveolar cells. <b>Methods</b>: ATP synthesis and cytochrome c oxidase (COX) activity, as a marker of mitochondrial function, was assessed in A549 cells pretreated with T2 and exposed to CS using a bioluminescence assay and an Oroboros 2k-Oxygraph system, respectively. An evaluation of the oxidative status was conducted by assessing superoxide radical production, superoxide dismutase (SOD) activity, and H<sub>2</sub>O<sub>2</sub> levels. Moreover, we investigated the mitochondrial mass via Mito-Tracker Green (MTG) staining and flow cytometry analysis. <b>Results</b>: CS significantly reduced ATP production. T2 pretreatment was found to prevent CS-induced impairments in ATP synthesis, enhancing COX activity. Additionally, the 2 h T2 pretreatment of CS-exposed cells mitigated CS-induced oxidative stress, thereby enhancing SOD activity and reducing the superoxide anion and H<sub>2</sub>O<sub>2</sub> levels. Finally, MTG labeling was correlated with CS-induced mitochondrial mass gain, which is associated with cell senescence. Unexpectedly, T2 was not able to significantly prevent this mass increment, probably due to its rapid mode of action. <b>Conclusions</b>: Our results provide new insights into the protective effects of T2 against CS-induced mitochondrial damage. |
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| ISSN: | 2227-9059 |