A versatile EPR toolbox for the simultaneous measurement of oxygen consumption and superoxide production

d’Hose, Donatienne; Danhier, Pierre; Northshield, Heidi; Isenborghs, Pauline; Jordan, Bénédicte F.; Gallez, Bernard

doi:10.1016/j.redox.2020.101852

Cited by 10 publications

(7 citation statements)

References 41 publications

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“…In this study, we found that SiO 2 exposure significantly increased the level of intracellular ROS and the release of pro-inflammatory cytokines, which was effectively attenuated after the metformin treatment. Similarly, other studies have also elucidated the antioxidative and anti-inflammatory properties of metformin in different experimental models [ 63 – 65 ]. For example, metformin attenuates hypoxia-induced mitochondrial ROS in different cell lines by modulating the hypoxia-inducible factor-1alpha (HIF-1α) pathway [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling

Cheng

Wang

et al. 2021

J Transl Med

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Background Silicosis is one of the most common occupational pulmonary fibrosis caused by respirable silica-based particle exposure, with no ideal drugs at present. Metformin, a commonly used biguanide antidiabetic agent, could activate AMP-activated protein kinase (AMPK) to exert its pharmacological action. Therefore, we sought to investigate the role of metformin in silica-induced lung fibrosis. Methods The anti-fibrotic role of metformin was assessed in 50 mg/kg silica-induced lung fibrosis model. Silicon dioxide (SiO2)-stimulated lung epithelial cells/macrophages and transforming growth factor-beta 1 (TGF-β1)-induced differentiated lung fibroblasts were used for in vitro models. Results At the concentration of 300 mg/kg in the mouse model, metformin significantly reduced lung inflammation and fibrosis in SiO2-instilled mice at the early and late fibrotic stages. Besides, metformin (range 2–10 mM) reversed SiO2-induced cell toxicity, oxidative stress, and epithelial-mesenchymal transition process in epithelial cells (A549 and HBE), inhibited inflammation response in macrophages (THP-1), and alleviated TGF-β1-stimulated fibroblast activation in lung fibroblasts (MRC-5) via an AMPK-dependent pathway. Conclusions In this study, we identified that metformin might be a potential drug for silicosis treatment.

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Section: Discussionmentioning

confidence: 99%

Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling

Cheng

Wang

et al. 2021

J Transl Med

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“…Interestingly, some SDH blockers (such as α-tocopheryl succinate, vitamin E-derived compounds linked to triphenylphosphonium group, malonate, 3-nitropropionate, lonidamine) have been evaluated in cancer therapy because the leakage of electrons to molecular oxygen leads to excessive production of superoxide ions and cancer cell apoptosis [15][16][17][18][19][20]. Hypothesizing that SDHIs-fungicides may present a similar mode of action, we used Electron Paramagnetic Resonance (EPR) spectroscopy which is particularly suitable to assess the oxygen consumption rate (OCR) [21][22][23] as well as the production of mitochondrial superoxide [23][24][25][26][27][28][29]. In addition, we evaluated the impact of short-term exposure to SDHIs on cell apoptosis and necrosis.…”

Section: Introductionmentioning

confidence: 99%

The Short-Term Exposure to SDHI Fungicides Boscalid and Bixafen Induces a Mitochondrial Dysfunction in Selective Human Cell Lines

et al. 2021

Self Cite

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Fungicides are used to suppress the growth of fungi for crop protection. The most widely used fungicides are succinate dehydrogenase inhibitors (SDHIs) that act by blocking succinate dehydrogenase, the complex II of the mitochondrial electron transport chain. As recent reports suggested that SDHI-fungicides could not be selective for their fungi targets, we tested the mitochondrial function of human cells (Peripheral Blood Mononuclear Cells or PBMCs, HepG2 liver cells, and BJ-fibroblasts) after exposure for a short time to Boscalid and Bixafen, the two most used SDHIs. Electron Paramagnetic Resonance (EPR) spectroscopy was used to assess the oxygen consumption rate (OCR) and the level of mitochondrial superoxide radical. The OCR was significantly decreased in the three cell lines after exposure to both SDHIs. The level of mitochondrial superoxide increased in HepG2 after Boscalid and Bixafen exposure. In BJ-fibroblasts, mitochondrial superoxide was increased after Bixafen exposure, but not after Boscalid. No significant increase in mitochondrial superoxide was observed in PBMCs. Flow cytometry revealed an increase in the number of early apoptotic cells in HepG2 exposed to both SDHIs, but not in PBMCs and BJ-fibroblasts, results consistent with the high level of mitochondrial superoxide found in HepG2 cells after exposure. In conclusion, short-term exposure to Boscalid and Bixafen induces a mitochondrial dysfunction in human cells.

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“…Moreover, SiO2 treatment increased macrophage's IL-1β and TNF-α levels, which were associated with the severity of lung in ammation. Similarly, other studies have also elucidated the antioxidative and anti-in ammatory properties of metformin in different experimental models [50][51][52]. For example, metformin attenuates hypoxia-induced mitochondrial ROS in different cell lines by modulating the HIF-1α pathway [53].…”

Section: Discussionmentioning

confidence: 96%

Metformin Attenuates Silica-induced Pulmonary Fibrosis via AMPK Signaling

Cheng

Wang

et al. 2021

Preprint

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Background: Silicosis is one of the most common occupational pulmonary fibrosis caused by respirable silica-based particle exposure, with no ideal drugs at present. Metformin, a commonly used biguanide antidiabetic agent, could activate AMP-activated protein kinase (AMPK) to exert its pharmacological action. Therefore, we sought to investigate the role of metformin in silica-induced lung fibrosis.Methods: The anti-fibrotic role of metformin was assessed in 50 mg/kg silica-induced lung fibrosis model. SiO2-stimulated lung epithelial cells/macrophages and TGF-β-induced differentiated lung fibroblasts were used for in vitro models.Results: At the concentration of 300 mg/kg in the mouse model, metformin significantly reduced lung inflammation and fibrosis in SiO2-instilled mice at the early and late fibrotic stages. Besides, metformin (range 2mM to 10mM) reversed SiO2-induced cell toxicity, oxidative stress, and epithelial-mesenchymal transition process in epithelial cells (A549 and HBE), inhibited inflammation response in macrophages (THP-1), and alleviated TGF-β1-stimulated fibroblast activation in lung fibroblasts (MRC-5) via an AMPK-dependent pathway.Conclusions: In this study, we identified that metformin might be a potential drug for silicosis treatment.

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A versatile EPR toolbox for the simultaneous measurement of oxygen consumption and superoxide production

Cited by 10 publications

References 41 publications

Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling

Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling

The Short-Term Exposure to SDHI Fungicides Boscalid and Bixafen Induces a Mitochondrial Dysfunction in Selective Human Cell Lines

Metformin Attenuates Silica-induced Pulmonary Fibrosis via AMPK Signaling

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