Melatonin attenuates lipopolysaccharide‐induced acute lung inflammation in sleep‐deprived mice

Abstract

Sleep disorders are great problems in modern society. Even minimal changes of sleep can affect health. Especially, patients with pulmonary diseases complain of sleep problems such as sleep disturbance and insomnia. Recent studies have shown an association between sleep deprivation (SD) and inflammation, however, the underlying mechanisms remain unclear. In the present study, we investigated whether melatonin protects against acute lung inflammation in SD. Male ICR mice were deprived sleep using modified multiplatform water bath for 3 days. Acute lung inflammation was induced by lipopolysaccharide (LPS; 5 mg/kg). Melatonin (5 mg/kg) and LPS was administered in SD mice at day 2. Mice were divided into five groups as control, SD, LPS, LPS + SD, and LPS + SD + melatonin (each group, n = 11). Mice were killed on day 3 after treatment of melatonin and LPS for 24 hr. Lung tissues were collected for histological examination and protein analysis. The malondialdehyde (MDA) level was determined for the effect of oxidative stress. Melatonin restored weight loss in LPS + SD. Histological findings revealed alveolar damages with inflammatory cell infiltration in LPS + SD. Melatonin remarkably attenuated the alveolar damages. In western blot analysis, LPS reduced the levels of Bcl-XL and procaspase-3 in SD mice. After treatment with melatonin, the levels of Bcl-XL and procaspase-3 increased when compared with LPS + SD. LPS treatment showed an increase of TUNEL-positive cells, whereas melatonin prevented the increase of cell death in LPS + SD animals. In lipid peroxidation assay, melatonin significantly reduced the elevated MDA level in LPS + SD. Our results suggest that melatonin attenuates acute lung inflammation during SD via anti-apoptotic and anti-oxidative actions.

Impact of melatonin on immunity: a review

“…The aforementioned inhibition of iNOS can be cited as another target for the anti-inflammatory effect. Using ICR mice as a model, melatonin was found to be able to reduce inflammatory process in lungs treated with lipopolysaccharide [53]. The study concluded with the statement that melatonin can act as an anti-inflammatory drug by means of interfering lipopolysaccharide-initiated reduction of Bcl-XL and procaspase-3.…”

Melatonin protects against oxidative damage in a neonatal rat model of bronchopulmonary dysplasia

“…Pathophysiology and pathogenesis of BPD have been substantially understood, and upon recognition of ROS in the pathogenesis of BPD, [10] major efforts have been made to fi nd antioxidants for the prevention or mitigation of BPD, but not all of them have proven benefi cial and thus more novel approaches are therefore warranted. [11] MT that can prevent lung injury and brain damage in many adult animal models [12][13][14][15][16][17] is also thought to be a good candidate for studies in human newborns at risk for developing lung disease. In the present study, we assessed whether exogenous MT during hyperoxia exposure would attenuate hyperoxia-induced lung injury in neonatal rats.…”

Melatonin improves inflammatory cytokine profiles in lung inflammation associated with sleep deprivation

“…In a previous study, we reported that melatonin protects the lung against inflammation associated with SD in mouse lung Melatonin improves inflammatory cytokine profiles in lung inflammation associated with sleep deprivation tissue (7). In order to reinforce our previous report, the aim of the present study was to determine the pro-inflammatory cytokine levels in sera and alveoli.…”

“…The association between SD and lung inflammation has been studied. SD aggravates acute lung inflammation induced by lipopolysaccharide (LPS), including inflammatory cell infiltration, elevated apoptosis and membrane hyper-peroxidation (7). Even a subtle amount of sleep loss alters molecular processes that drive cellular immune activation and induce inflammatory cytokines (8).…”