Enhanced fatty acid oxidation through Metformin and Baicalin as therapy for COVID-19 and associated inflammatory states in lung and kidney
Free Radical Biology and Medicine
; 201(Supplement 1):46, 2023.
Article
in English
| EMBASE | ID: covidwho-2324939
ABSTRACT
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 and ultimate tissue scarring. Energy balance may be crucial for the recovery of clinical COVID-19. Hence, we asked if two key pathways involved in 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 COVID19 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-beta-induced fibrosis, apoptosis and inflammation markers in lung epithelial cells. Similar results were observed with two new indole derivatives IND6 and IND8 with AMPK activating capacity. Consistently, a reduced stay in the intensive care unit was observed in COVID-19 patients previously exposed to Metformin. Baicalin also reduced kidney fibrosis in two animal models of kidney injury, another key target of COVID-19, while in vitro both drugs improved mitochondrial function and prevented TGF-beta-induced renal epithelial cell dedifferentiation. Our results support that strategies based on energy supply may prove useful in the prevention of COVID-19-induced lung and renal damage.Copyright © 2023
adult; adult respiratory distress syndrome; animal cell; animal experiment; animal model; apoptosis; cell dedifferentiation; cohort analysis; conference abstract; controlled study; coronavirus disease 2019; drug combination; drug therapy; energy resource; enzyme activity; epithelium cell; fatty acid oxidation; female; human; in vitro study; inflammation; intensive care unit; kidney fibrosis; kidney injury; lung injury; male; mitochondrion; nonhuman; pneumonia; prevention; protein function; signal transduction; acetyl coenzyme A carboxylase; baicalin; carnitine palmitoyltransferase I; endogenous compound; hydroxymethylglutaryl coenzyme A reductase kinase; indole derivative; metformin; transforming growth factor beta
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Type of study:
Cohort study
/
Observational study
/
Prognostic study
Language:
English
Journal:
Free Radical Biology and Medicine
Year:
2023
Document Type:
Article
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