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Updated: Jun 22, 2026
Non-Invasive Endotracheal Administration of Lipopolysaccharide to Induce Acute Lung Injury in Rodents
Published on: December 5, 2025
Melatonin reduces acute lung injury in endotoxemic rats
You Shang1, San-Peng Xu, Yan Wu
1Department of Anaesthesiology and Intensive Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
Background:
Treatment with melatonin significantly reduces lung injury induced by bleomycin, paraquat and ischemia reperfusion. In the present study, we investigated the possible protective roles of melatonin in pulmonary inflammation and lung injury during acute endotoxemia.
Methods:
Thirty-two male Sprague-Dawley rats were randomly assigned to four groups: vehicle + saline group, melatonin + saline group, vehicle + lipopolysaccharide group, melatonin + lipopolysaccharide group. The rats were treated with melatonin (10 mg/kg, intraperitoneal injection (i.p.)) or vehicle (1% ethanol saline), 30 minutes prior to lipopolysaccharide administration (6 mg/kg, intravenous injection). Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Blood gas analysis was carried out. Optical microscopy was performed to examine pathological changes in lungs and lung injury score was assessed. Wet/dry ratios (W/D), myeloperoxidase activity, malondialdehyde concentrations and tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) levels in lungs were measured. The pulmonary expression of nuclear factor-kappa B (NF-kappaB) p65 was evaluated by Western blotting.
Results:
PaO(2) in the vehicle + lipopolysaccharide group decreased compared with that in the vehicle + saline group. This decrease was significantly reduced in the melatonin + lipopolysaccharide group. The lung tissues from the saline + lipopolysaccharide group were significantly damaged, which were less pronounced in the melatonin + lipopolysaccharide group. The W/D ratio increased significantly in the vehicle + lipopolysaccharide group (6.1 +/- 0.18) as compared with that in the vehicle + saline group (3.61 +/- 0.3) (P < 0.01), which was significantly reduced in the melatonin + lipopolysaccharide group (4.8 +/- 0.25) (P < 0.01). Myeloperoxidase activity and malondialdehyde levels increased significantly in the vehicle + lipopolysaccharide group compared with that in the vehicle + saline group, which was reduced in the melatonin + lipopolysaccharide group. The TNF-alpha level of pulmonary tissue increased significantly in the vehicle + lipopolysaccharide group ((8.7 +/- 0.91) pg/mg protein) compared with that in the vehicle + saline group ((4.3 +/- 0.62) pg/mg protein, P < 0.01). However, the increase of TNF-alpha level of pulmonary tissue was significantly reduced in the melatonin + lipopolysaccharide group ((5.9 +/- 0.56) pg/mg protein, P < 0.01). Pulmonary IL-10 levels were elevated markedly in the vehicle + lipopolysaccharide group in contrast to that in the vehicle + saline group, whereas the elevation was augmented in the melatonin + lipopolysaccharide group. The nuclear localization of p65 increased markedly in the vehicle + lipopolysaccharide group and this enhancement of nuclear p65 expression was much less in the melatonin + lipopolysaccharide group.
Conclusion:
Melatonin reduces acute lung injury in endotoxemic rats by attenuating pulmonary inflammation and inhibiting NF-kappaB activation.
Insights
Melatonin treatment significantly reduced acute lung injury in endotoxemic rats. This protective effect was achieved by decreasing pulmonary inflammation and inhibiting nuclear factor-kappa B (NF-kappaB) activation.
Area of Science:
- Pulmonary Medicine
- Pharmacology
- Toxicology
Background:
- Melatonin is known to mitigate lung injury from various insults.
- This study investigated melatonin's protective effects against endotoxemia-induced pulmonary inflammation and injury.
Purpose of the Study:
- To evaluate the efficacy of melatonin in preventing acute lung injury during endotoxemia.
- To elucidate the mechanisms underlying melatonin's protective role in endotoxemic lung injury.
Main Methods:
- Male Sprague-Dawley rats were divided into four groups: saline or lipopolysaccharide (LPS) with or without melatonin treatment.
- Melatonin (10 mg/kg) or vehicle was administered intraperitoneally 30 minutes before LPS (6 mg/kg) intravenous injection.
- Lung tissues were analyzed for pathological changes, wet/dry ratio, myeloperoxidase activity, malondialdehyde, TNF-alpha, IL-10, and NF-kappaB p65 expression.
Main Results:
- Melatonin treatment significantly improved oxygenation (PaO2) and reduced lung injury scores and wet/dry ratios in LPS-challenged rats.
- Melatonin administration decreased myeloperoxidase activity, malondialdehyde, and TNF-alpha levels, while augmenting IL-10 levels.
- Inhibition of NF-kappaB p65 nuclear translocation was observed in rats treated with melatonin.
Conclusions:
- Melatonin demonstrates significant protective effects against acute lung injury in an endotoxemic rat model.
- The observed benefits are attributed to melatonin's ability to attenuate pulmonary inflammation and suppress NF-kappaB activation.
