CDP-choline reduces severity of intestinal injury in a neonatal rat model of necrotizing enterocolitis

被引:26
|
作者
Cetinkaya, Merih [1 ]
Cansev, Mehmet [2 ]
Cekmez, Ferhat [1 ]
Tayman, Cuneyt [2 ]
Canpolat, Fuat Emre [1 ]
Kafa, Ilker M. [3 ]
Uysal, Sema [4 ]
Tunc, Turan [1 ]
Sarici, S. Umit [1 ]
机构
[1] Gulhane Mil Med Acad, Dept Pediat, Div Neonatol, TR-06017 Ankara, Turkey
[2] Uludag Univ, Fac Med, Dept Pharmacol, Bursa, Turkey
[3] Uludag Univ, Dept Anat, Fac Med, Bursa, Turkey
[4] Fatih Univ, Dept Biochem, Fac Med, Ankara, Turkey
关键词
Necrotizing enterocolitis; CDP-choline; Neonatal rat; Inflammation; Apoptosis; ULCERATIVE-COLITIS; INFLAMMATORY RESPONSE; ISCHEMIA-REPERFUSION; MUCUS BARRIER; PHOSPHATIDYLCHOLINE; CYTIDINE; APOPTOSIS; MECHANISMS; CITICOLINE; NECROSIS;
D O I
10.1016/j.jss.2012.11.032
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background: Cytidine 5'-diphosphocholine (CDP-choline) is an endogenous intermediate in the biosynthesis of phosphatidylcholine, a contributor to the mucosal defense of the intestine. The aim of this study was to evaluate the possible cytoprotective effect of CDP-choline treatment on intestinal cell damage, membrane phospholipid content, inflammation, and apoptosis in a neonatal rat model of necrotizing enterocolitis (NEC). Methods: We divided a total of 30 newborn pups into three groups: control, NEC, and NEC + CDP-choline. We induced NEC by enteral formula feeding, exposure to hypoxia-hyperoxia, and cold stress. We administered CDP-choline intraperitoneally at 300 mg/kg/d for 3 d starting from the first day of life. We evaluated apoptosis macroscopically and histopathologically in combination with proinflammatory cytokines in the gut samples. Moreover, we determined membrane phospholipid levels as well as activities of xanthine oxidase, superoxide dismutase, glutathione peroxidase, and myeloperoxidase enzymes and the malondialdehyde content of intestinal tissue. Results: Mean clinical sickness score, macroscopic gut assessment score, and intestinal injury score were significantly improved, whereas mean apoptosis score and caspase-3 levels were significantly reduced in pups in the NEC + CDP-choline group compared with the NEC group. Tissue proinflammatory cytokine (interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha) levels as well as tissue malondialdehyde content and myeloperoxidase activities were reduced, whereas glutathione peroxidase and superoxide dismutase activities were preserved in the NEC + CDP-choline group. In addition, NEC damage reduced intestinal tissue membrane phospholipids, whereas CDP-choline significantly enhanced total phospholipid and phosphatidylcholine levels. Long-term follow-up in additional experiments revealed increased body weight, decreased clinical sickness scores, and enhanced survival in CDP-cholineereceiving versus saline-receiving pups with NEC lesions. Conclusions: Our study reports, for the first time, beneficial effects of CDP-choline treatment on intestinal injury in a neonatal rat model of NEC. Our data suggest that CDP-choline may be used as an effective therapeutic agent to prevent NEC. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码:119 / 128
页数:10
相关论文
共 50 条
  • [41] Neonatal intestinal dysbiosis in necrotizing enterocolitis
    Naomi-Liza Denning
    Jose M. Prince
    Molecular Medicine, 2018, 24
  • [42] EFFECTS OF CDP-CHOLINE ON THE RECOVERY OF PATIENTS WITH HEAD-INJURY
    MALDONADO, VC
    PEREZ, JBC
    ESCARIO, JA
    JOURNAL OF THE NEUROLOGICAL SCIENCES, 1991, 103 : S15 - S18
  • [43] Melatonin ameliorates necrotizing enterocolitis in a neonatal rat model
    Guven, Ahmet
    Uysal, Bulent
    Gundogdu, Gokhan
    Oztas, Emin
    Ozturk, Haluk
    Korkmaz, Ahmet
    JOURNAL OF PEDIATRIC SURGERY, 2011, 46 (11) : 2101 - 2107
  • [44] Neonatal intestinal dysbiosis in necrotizing enterocolitis
    Denning, Naomi-Liza
    Prince, Jose M.
    MOLECULAR MEDICINE, 2018, 24
  • [45] Human β-defensin-3 promotes intestinal epithelial cell migration and reduces the development of necrotizing enterocolitis in a neonatal rat model
    Qingfeng Sheng
    Zhibao Lv
    Wei Cai
    Huanlei Song
    Linxi Qian
    Huaibo Mu
    Jingyi Shi
    Xueli Wang
    Pediatric Research, 2014, 76 : 269 - 279
  • [46] Human β-defensin-3 promotes intestinal epithelial cell migration and reduces the development of necrotizing enterocolitis in a neonatal rat model
    Sheng, Qingfeng
    Lv, Zhibao
    Cai, Wei
    Song, Huanlei
    Qian, Linxi
    Mu, Huaibo
    Shi, Jingyi
    Wang, Xueli
    PEDIATRIC RESEARCH, 2014, 76 (03) : 269 - 279
  • [47] ACTION OF CDP-CHOLINE BY INTRADUODENAL ROUTE ON RAT CARDIORESPIRATORY SYSTEM
    BRASO, MA
    SACRISTAN, A
    ORTIZ, JA
    ARZNEIMITTEL-FORSCHUNG/DRUG RESEARCH, 1983, 33-2 (7A): : 1043 - 1045
  • [48] NESFATIN-1 AMELIORATES BOWEL INJURY IN A NEONATAL RAT MODEL OF NECROTIZING ENTEROCOLITIS
    Cerit, Kivilcim Karadeniz
    Koyuncuoglu, Turkan
    Yagmur, Damla
    Anil, Damla
    Sirvanci, Serap
    Dagli, Tolga
    Yegen, Berrak C.
    GASTROENTEROLOGY, 2017, 152 (05) : S621 - S621
  • [49] Recombinant human soluble thrombomodulin reduces the severity and incidence of necrotizing enterocolitis in a newborn rat model
    Bo Li
    Ryuta Saka
    Yuichi Takama
    Takehisa Ueno
    Yuko Tazuke
    Hiroomi Okuyama
    Surgery Today, 2019, 49 : 971 - 976
  • [50] Recombinant human soluble thrombomodulin reduces the severity and incidence of necrotizing enterocolitis in a newborn rat model
    Li, Bo
    Saka, Ryuta
    Takama, Yuichi
    Ueno, Takehisa
    Tazuke, Yuko
    Okuyama, Hiroomi
    SURGERY TODAY, 2019, 49 (11) : 971 - 976