Academic Journal
Enhanced fatty acid oxidation through metformin and baicalin as therapy for COVID-19 and associated inflammatory states in lung and kidney
| Title: | Enhanced fatty acid oxidation through metformin and baicalin as therapy for COVID-19 and associated inflammatory states in lung and kidney |
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| Authors: | Verónica Miguel, Carlos Rey-Serra, Jessica Tituaña, Belén Sirera, Elena Alcalde-Estévez, J. Ignacio Herrero, Irene Ranz, Laura Fernández, Carolina Castillo, Lucía Sevilla, James Nagai, Katharina C. Reimer, Jitske Jansen, Rafael Kramann, Ivan G. Costa, Ana Castro, David Sancho, José Miguel Rodríguez González-Moro, Santiago Lamas |
| Source: | Redox Biology, Vol 68, Iss , Pp 102957- (2023) |
| Publisher Information: | Elsevier, 2023. |
| Publication Year: | 2023 |
| Collection: | LCC:Medicine (General) LCC:Biology (General) |
| Subject Terms: | Fibrosis, Metabolism, Mitochondria, Inflammation, COVID-19, Medicine (General), R5-920, Biology (General), QH301-705.5 |
| More Details: | Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (COVID-19) pandemic. It is the final outcome of the acute respiratory distress syndrome (ARDS), characterized by an initial exacerbated inflammatory response, metabolic derangement and ultimate tissue scarring. A positive balance of cellular energy may result crucial for the recovery of clinical COVID-19. Hence, we asked if two key pathways involved in cellular energy generation, AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling and fatty acid oxidation (FAO) could be beneficial. We tested the drugs metformin (AMPK activator) and baicalin (CPT1A activator) in different experimental models mimicking COVID-19 associated inflammation in lung and kidney. We also studied two different cohorts of COVID-19 patients that had been previously treated with metformin. These drugs ameliorated lung damage in an ARDS animal model, while activation of AMPK/ACC signaling increased mitochondrial function and decreased TGF-β-induced fibrosis, apoptosis and inflammation markers in lung epithelial cells. Similar results were observed with two indole derivatives, IND6 and IND8 with AMPK activating capacity. Consistently, a reduced time of hospitalization and need of intensive care was observed in COVID-19 patients previously exposed to metformin. Baicalin also mitigated the activation of pro-inflammatory bone marrow-derived macrophages (BMDMs) and reduced kidney fibrosis in two animal models of kidney injury, another key target of COVID-19. In human epithelial lung and kidney cells, both drugs improved mitochondrial function and prevented TGF-β-induced renal epithelial cell dedifferentiation. Our results support that favoring cellular energy production through enhanced FAO may prove useful in the prevention of COVID-19-induced lung and renal damage. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2213-2317 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2213231723003580; https://doaj.org/toc/2213-2317 |
| DOI: | 10.1016/j.redox.2023.102957 |
| Access URL: | https://doaj.org/article/a3d2c910d76043b19ac7d4579c3da8a2 |
| Accession Number: | edsdoj.3d2c910d76043b19ac7d4579c3da8a2 |
| Database: | Directory of Open Access Journals |
| ISSN: | 22132317 |
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| DOI: | 10.1016/j.redox.2023.102957 |
| Published in: | Redox Biology |
| Language: | English |