Therapeutic Effects of Lycopene on Lipopolysaccharide-Induced Acute Lung Injury: Regulation of the PINK1/Parkin Signaling Pathway and Mitochondrial Autophagy

JOURNAL OF BIOMEDICAL NANOTECHNOLOGY(2023)

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Abstract
This study investigates the mechanism underlying the therapeutic effects of lycopene (Lyc) on lipopolysaccharide (LPS)induced acute lung injury (ALI). ALI cell models were established using A549 cells treated with LPS. Cell viability was assessed using cell counting kit-8. ALI cells were treated with Lyc, mitochondrial autophagy inhibitor cyclosporine A (CsA), PTEN-induced kinase 1 (PINK1) activator Valinomycin, and reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC). Apoptosis was evaluated by flow cytometry and JC-1 probe staining. ROS and adenosine triphosphate levels were determined using dichloro-dihydro-fluorescein diacetate staining. Western blot assessed the expression levels of light chain 3 (LC3), Lysosomal-associated membrane protein 1, PINK1, and Parkin. An LPS-induced ALI rat model was treated with different concentrations of Lyc. Lung injury was assessed by hematoxylin and eosin staining. Levels of tumor necrosis IP: 2038 10920 On: Tue 05 Dec 2023 10:37:26 factor-a, interleukin-6, and lactate dehydrogenase wermeasured by ELISA combined with magnetic nanoparticles. In Copyright: Amercan Scientif c Publ shers this study, different concentrations of Lyc treatmentDeliveredenhanced by cellIngentasurvival. Additionally, Lyc treatment reduced the cell apoptosis rate, decreased lactate dehydrogenase (LDH) leakage and ROS level in ALI cells, and inhibited the expression of LC3, Beclin-1, PINK1, and Parkin. Consistent effects were seen in Lyc, CsA, Valinomycin, and NAC groups, suggesting similar impacts. In animal experiments, Lyc treatment significantly mitigated edema, inflammation, and autophagy in lung tissues. Furthermore, Lyc exhibited a protective effect on ALI cells by regulating PINK1/Parkin pathway and inhibiting mitochondrial autophagy. Overall, Lyc regulates mitochondrial autophagy in LPS-induced ALI with practical significance for studying its pharmacological mechanism and theoretical implications for understanding autophagy in ALI.
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Key words
Lipopolysaccharide,Lycopene,Mitophagy,Acute Lung Injury,PINK1-Parkin,Magnetic Nanoparticles ELISA
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