Related Experiment Video
Updated: Nov 30, 2025
Mouse Model of Oleic Acid-Induced Acute Respiratory Distress Syndrome
Published on: June 2, 2022
Oxycodone attenuates vascular leak and lung inflammation in a clinically relevant two-hit rat model of acute lung
Xinyi Li1, Rui Li2, Qing Fang1
1Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Background:
Oxycodone is a synthetic opioid receptor agonist that exerts antinociceptive activity via κ-, μ- and δ-opioid receptors (KOR, MOR and DOR, respectively). Activation of MOR has been reported to provide protection against acute lung injury (ALI). We hypothesized that pretreatment with oxycodone would attenuate lung injury at the level of alveolar tight junctions (TJs) and aquaporins (AQPs) and investigated this possibility in a two-hit model of ALI induced by lipopolysaccharide (LPS) and mechanical ventilation (MV).
Method:
Male Sprague Dawley rats and A59 cells were divided into 6 groups: the control group, ALI group, oxycodone-pretreated group, and oxycodone/κ-, μ-, or δ-opioid receptor antagonist-pretreated groups. The rats were pretreated with oxycodone 30 min before intravenous injection of LPS and then allowed to recover for 24 h prior to MV, establishing a two-hit model of ALI. The cells were similarly treated with oxycodone (with or without antagonists) 30 min after exposure to lipopolysaccharide. The cells were cyclically stretched 24 h later to mirror the in vivo MV protocol.
Results:
Oxycodone alleviated the histological lung changes in the rats with ALI and decreased pulmonary microvascular permeability both in vivo and in vitro. Oxycodone upregulated the expression of claudin-5, ZO-1, AQP1, and AQP5 but downregulated the expression of TNF-α, IL-1β, TLR4, NF-κB, MMP9, and caspase-3 and suppressed endothelial apoptosis in vivo and in vitro. These protective effects of oxycodone were partly eliminated by KOR and MOR antagonists but not by DOR antagonists.
Conclusion:
Oxycodone pretreatment appears to act via κ- and μ-opioid receptors to ameliorate LPS- and MV-induced lung injury by suppressing inflammation and apoptosis, and this protective effect might be mediated through the inhibition of the TLR4/NF-κB pathways.
Insights
Oxycodone pretreatment protects against acute lung injury (ALI) by modulating tight junctions and aquaporins. These effects are mediated through kappa- and mu-opioid receptors, reducing inflammation and apoptosis.
Area of Science:
- Pharmacology
- Pulmonary Medicine
- Cell Biology
Background:
- Acute lung injury (ALI) is a critical condition with significant morbidity and mortality.
- Opioid receptor agonists, like oxycodone, have shown potential in mitigating lung injury.
- The specific mechanisms involving tight junctions and aquaporins in oxycodone's protective effects against ALI require further elucidation.
Purpose of the Study:
- To investigate the protective effects of oxycodone pretreatment on lipopolysaccharide (LPS) and mechanical ventilation (MV)-induced ALI.
- To determine if oxycodone modulates alveolar tight junctions (TJs) and aquaporins (AQPs) in the context of ALI.
- To explore the involvement of kappa (KOR), mu (MOR), and delta (DOR) opioid receptors in oxycodone's protective actions.
Main Methods:
- A two-hit model of ALI was established in Sprague Dawley rats and A59 cells using LPS and MV.
- Animals and cells were pretreated with oxycodone, with or without specific opioid receptor antagonists (KOR, MOR, DOR).
- Histological lung changes, pulmonary microvascular permeability, TJ and AQP expression, inflammatory markers, and apoptosis were assessed.
Main Results:
- Oxycodone pretreatment alleviated lung injury, reduced microvascular permeability, and suppressed inflammation and apoptosis in ALI models.
- Oxycodone upregulated tight junction proteins (claudin-5, ZO-1) and aquaporins (AQP1, AQP5).
- The protective effects were diminished by KOR and MOR antagonists, but not by DOR antagonists, suggesting KOR and MOR mediation.
Conclusions:
- Oxycodone pretreatment ameliorates LPS- and MV-induced lung injury.
- The protective mechanisms involve the modulation of tight junctions, aquaporins, inflammation, and apoptosis via KOR and MOR.
- Oxycodone may exert its effects by inhibiting the TLR4/NF-κB signaling pathways.
Related Concept Videos
01:15Opioid Analgesics: Synthetic and Semisynthetic Opioids
01:25Analgesia and Pain Management