Melatonin alleviates oxidative stress in sleep deprived mice: Involvement of small intestinal mucosa injury

Int Immunopharmacol. 2020 Jan;78:106041. doi: 10.1016/j.intimp.2019.106041. Epub 2019 Dec 10.


Background: Previous research demonstrated that sleep deprivation (SD) resulted in intestinal homeostasis disorder in colon. The present study was further performed to clarify the role of melatonin in SD-induced small intestinal (SI) mucosal injury.

Methods: We successfully established a multiplatform 72 h SD mouse model with or without melatonin supplementation to explore the improvement of melatonin in the destruction of SI induced by SD.

Results: Melatonin supplementation suppressed an increase of corticosterone level and a decrease of melatonin level caused by SD. Meanwhile, we observed that melatonin supplementation in sleep deprived mice markedly reversed a decrease of the villi length/crypt depth (V/C) ratio and the number of goblet cells, PCNA positive cells, the expressions of MUC2 and tight junction proteins, as well as an upregulation of the expressions of autophagic proteins in the duodenum, jejunum and ileum. Furthermore, melatonin supplementation inverted the SD-induced the decline of antioxidant enzyme activities (T-AOC and CAT etc) and anti-inflammatory cytokines (IL-10 and IFN-γ) and the increase of oxidative product MDA, pro-inflammatory cytokines (IL-6 and TNF-α), p-P65 and p-IκB proteins in the SI.

Conclusions: These findings suggested that melatonin may be used as a probiotic agent to reverse SD-induced SI mucosa injury by suppressing oxidative stress and NF-κB pathway activation.

Keywords: Intestinal mucosa injury; Melatonin; NF-κB; Oxidative stress; Sleep deprivation.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Enteritis / immunology
  • Enteritis / pathology
  • Enteritis / prevention & control*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology
  • Intestine, Small / drug effects
  • Intestine, Small / immunology
  • Intestine, Small / pathology
  • Male
  • Melatonin / administration & dosage*
  • Mice
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects
  • Oxidative Stress / immunology
  • Probiotics / administration & dosage*
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Sleep Deprivation / complications
  • Sleep Deprivation / drug therapy*
  • Sleep Deprivation / immunology


  • NF-kappa B
  • Melatonin