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Updated: Sep 10, 2025

Visualizing Lung Cellular Adaptations during Combined Ozone and LPS Induced Murine Acute Lung Injury
Published on: March 21, 2021
Oxycodone attenuates endotoxin-induced acute lung injury by regulating mitophagy via the HO-1 pathway
Cuicui Liu1, Yanting Wang2, Shaona Li2
1Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, China.
Background:
Endotoxin-induced Acute Lung Injury (ALI) is a severe clinical syndrome with limited treatment. Oxycodone can alleviate the endotoxin-induced ALI, but the exact mechanism remains unclear. The previous study showed that Heme Oxygenase-1 (HO-1) plays a protective role against endotoxin-induced ALI by regulating mitophagy. Thus, the authors aimed to elucidate whether oxycodone attenuates lung injury by regulating mitophagy via the HO-1 pathway.
Methods:
Lipopolysaccharide (LPS) ‒ stimulated mice and Mouse Lung Epithelial (MLE12) cells were used to create the model of ALI. After pre-treatment with Oxycodone for the LPS-induced model in vivo and in vitro, markers of cell and tissue damage, oxidative stress, inflammation, and mitophagy were detected. HO-1 knockout mice and HO-1 siRNA in vitro were used to further clarify the role of Oxycodone.
Results:
Pre-treatment with oxycodone could alleviate lung pathological damage, reduce oxidative stress and inflammatory cytokines, increase the expression of HO-1 while down-regulate the mitophagy-related proteins (PINK1, Parkin, LC3 II/I). Furthermore, treatment with oxycodone in HO-1-knockout mice or HO-1 siRNA-transfected MLE12 cells revealed the protective role of the HO-1 pathway on oxycodone-mediated mitophagy in LPS-induced ALI.
Conclusion:
HO-1 deficiency partially counteracts the beneficial effects of oxycodone on pulmonary protection and inhibition of mitophagy both in vivo and in vitro. Oxycodone pretreatment attenuated LPS-induced systemic inflammation and subsequent lung injury by regulating mitophagy via the HO-1 pathway.
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