Melatonin attenuates lipopolysaccharide-induced acute lung inflammation in sleep-deprived mice.
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.
Lee
Yang-Deok
YD
Department of Internal Medicine, Eulji University School of Medicine, Daejeon, Republic of Korea.
Kim
Ju-Young
JY
Lee
Ki-Ho
KH
Kwak
Yoon-Jin
YJ
Lee
Seong-Kyu
SK
Kim
Ok-Soon
OS
Song
Dae-Yong
DY
Lee
Ji-Hye
JH
Baik
Tai-Kyoung
TK
Kim
Byung-Joon
BJ
Kim
Ji-Young
JY
Baik
Haing-Woon
HW
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006651:Histocytochemistry; D020287:In Situ Nick-End Labeling; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D012892:Sleep Deprivation / Q000378:metabolism*
D008070:Lipopolysaccharides; D008315:Malondialdehyde; D008550:Melatonin