Melatonin improves experimental colitis with sleep deprivation

Park,Young-Sook; Chung,Sook-Hee; Lee,Seong-Kyu; Kim,Ja-Hyun; Kim,Jun-Bong; Kim,Tae-Kyun; Kim,Dong-Shin; Baik,Haing-Woon

doi:10.3892/ijmm.2015.2080

Melatonin improves experimental colitis with sleep deprivation

Authors:
- Young-Sook Park
- Sook-Hee Chung
- Seong-Kyu Lee
- Ja-Hyun Kim
- Jun-Bong Kim
- Tae-Kyun Kim
- Dong-Shin Kim
- Haing-Woon Baik
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Affiliations: Department of Gastroenterology, School of Medicine, Eulji University, Daejeon 301-746, Republic of Korea, Department of Gastroenterology, Ajou University School of Medicine, Suwon 443-721, Republic of Korea, Department of Biochemistry and Molecular Biology, School of Medicine, Eulji University, Daejeon 301-746, Republic of Korea
Published online on: January 27, 2015 https://doi.org/10.3892/ijmm.2015.2080
Pages: 979-986

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Abstract

Sleep deprivation (SD) is an epidemic phenomenon in modern countries, and its harmful effects are well known. SD acts as an aggravating factor in inflammatory bowel disease. Melatonin is a sleep-related neurohormone, also known to have antioxidant and anti-inflammatory effects in the gastrointestinal tract; however, the effects of melatonin on colitis have been poorly characterized. Thus, in this study, we assessed the measurable effects of SD on experimental colitis and the protective effects of melatonin. For this purpose, male imprinting control region (ICR) mice (n=24) were used; the mice were divided into 4 experimental groups as follows: the control, colitis, colitis with SD and colitis with SD and melatonin groups. Colitis was induced by the administration of 5% dextran sulfate sodium (DSS) in the drinking water for 6 days. The mice were sleep-deprived for 3 days. Changes in body weight, histological analyses of colon tissues and the expression levels of pro-inflammatory cytokines and genes were evaluated. SD aggravated inflammation and these effects were reversed by melatonin in the mice with colitis. In addition, weight loss in the mice with colitis with SD was significantly reduced by the injection of melatonin. Treatment with melatonin led to high survival rates in the mice, in spite of colitis with SD. The levels of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-17, interferon-γ and tumor necrosis factor-α, in the serum of mice were significantly increased by SD and reduced by melatonin treatment. The melatonin-treated group showed a histological improvement of inflammation. Upon gene analysis, the expression of the inflammatory genes, protein kinase Cζ (PKCζ) and calmodulin 3 (CALM3), was increased by SD, and the levels decreased following treatment with melatonin. The expression levels of the apoptosis-related inducible nitric oxide synthase (iNOS) and wingless-type MMTV integration site family, member 5A (Wnt5a) genes was decreased by SD, but increased following treatment with melatonin. Treatment with melatonin reduced weight loss and prolonged survival in mice with colitis with SD. Melatonin exerted systemic anti-inflammatory effects. Gene analysis revealed a possible mechanism of action of melatonin in inflammation and sleep disturbance. Thus, melatonin may be clinically applicable for patients with inflammatory bowel disease, particulary those suffering from sleep disturbances.

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