title: Melatonin attenuates intestinal ischemia--reperfusion-induced lung injury in rats by upregulating N-myc downstream-regulated gene 2.
abstract: BACKGROUND
  Successful drug treatment for ischemia--reperfusion-induced lung injury remains a major clinical problem. Melatonin (MT) is a hormone that is principally synthesized in the pineal gland. It has been shown to exhibit a variety of functions including anti-inflammatory and antioxidant effects. Previous reports on N-myc downstream-regulated gene (NDRG)2 have suggested that it is involved in cellular differentiation, development, antiapoptosis, anti-inflammatory cytokine, and antioxidant. The objective of this study was to test whether MT, a novel NDRG2 activator, can protect against intestinal ischemia-reperfusion-induced lung injury (IIRI).
  
  
  METHODS
  IIRI was induced in rats by occlusion of the superior mesenteric artery for 60 min, and the occlusion was then released for reperfusion. Rats were randomly divided into six groups as follows: control group; MT group; IIRI group; IIRI+5 mg/kg MT group; IIRI+15 mg/kg MT group; and IIRI+25 mg/kg MT group. The effects of MT on intestinal ischemia-reperfusion-induced lung pathologic changes, inflammatory cytokines release, myeloperoxidase and superoxide dismutase activities, and malondialdehyde level were examined. In addition, the NDRG2 activation in lung tissues was detected by Western blot analysis.
  
  
  RESULTS
  MT pretreatment attenuated edema and the pathologic changes in the lung. MT also decreased the levels of tumor necrosis factor-α, interleukin-1β, and interleukin-8 in bronchoalveolar lavage fluid. In addition, MT markedly prevented IIRI-induced elevation of malondialdehyde and myeloperoxidase levels, as well as reduction of superoxide dismutase activity. Furthermore, the expression of NDRG2 was activated by MT pretreatment in lung tissues.
  
  
  CONCLUSIONS
  The present study demonstrates that MT exerted protection against IIRI-induced oxidative stress. The potential mechanism of this action may attribute partly to the activation of NDRG2 expression.
authors.affiliation: Department of Thoracic Surgery, Tianjin First Center Hospital, Tianjin, PR China; Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shannxi Province, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shannxi Province, PR China.
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Ni
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shannxi Province, PR China.
authors.forename: Wen-Chen
authors.initials: WC
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Tianjin First Center Hospital, Tianjin, PR China.
authors.forename: Hong-Yin
authors.initials: HY
authors.lastname: Du
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shannxi Province, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Tianjin First Center Hospital, Tianjin, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Tianjin First Center Hospital, Tianjin, PR China. Electronic address: zhangweidongchest@163.com.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shannxi Province, PR China. Electronic address: jiangtaochest@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
mesh_terms: D000818:Animals; D016207:Cytokines / Q000032:analysis; D007422:Intestines / Q000098:blood supply*; D008168:Lung / Q000473:pathology; D055370:Lung Injury / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008550:Melatonin / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; C507213:Ndrg2 protein, rat; D009419:Nerve Tissue Proteins; D008315:Malondialdehyde; D009195:Peroxidase; D008550:Melatonin
keywords: IIRI; Melatonin; NDRG2; Oxidative stress