Alpha-lipoic acid attenuates silica-induced pulmonary fibrosis by improving mitochondrial function via AMPK/PGC1α pathway activation in C57BL/6J mice.
Toxicol Lett
; 350: 121-132, 2021 Oct 10.
Article
in En
| MEDLINE
| ID: mdl-34252510
Silicosis is characterized by pulmonary interstitial fibrosis that arises as a result of chronic exposure to silica. The few available treatments only delay its progression. As α-lipoic acid (ALA) has been shown to have various beneficial effects, including mitoprotective, antioxidant, and anti-inflammatory effects, we hypothesized that it may exhibit therapeutic effects in pulmonary fibrosis. Therefore, in the present study, we used a murine model of silicosis to investigate whether supplementation with exogenous ALA could attenuate silica-induced pulmonary fibrosis by improving mitochondrial function. ALA was administered to the model mice via continuous intragastric administration for 28 days, and then the antioxidant and mitoprotective effects of ALA were evaluated. The results showed that ALA decreased the production of reactive oxygen species, protected mitochondria from silica-induced dysfunction, and inhibited extracellular matrix deposition. ALA also decreased hyperglycemia and hyperlipidemia. Activation of the mitochondrial AMPK/PGC1α pathway might be responsible for these ALA-mediated anti-fibrotic effects. Exogenous ALA blocked oxidative stress by activating NRF2. Taken together, these findings demonstrate that exogenous ALA effectively prevents the progression of silicosis in a murine model, likely by stimulating mitochondrial biogenesis and endogenous antioxidant responses. Therefore, ALA can potentially delay the progression of silica-induced pulmonary fibrosis.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Pulmonary Fibrosis
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Silicosis
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Thioctic Acid
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Silicon Dioxide
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AMP-Activated Protein Kinases
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Mitochondria
Type of study:
Prognostic_studies
Language:
En
Journal:
Toxicol Lett
Year:
2021
Type:
Article