Melatonin reduces acute lung injury in endotoxemic rats / 中华医学杂志(英文版)

ABSTRACT

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Melatonin reduces acute lung injury in endotoxemic rats by attenuating pulmonary inflammation and inhibiting NF-kappaB activation.</p>