title: CDP-choline reduces severity of intestinal injury in a neonatal rat model of necrotizing enterocolitis.
abstract: 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-1β, interleukin-6, and tumor necrosis factor-α) 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-choline-receiving 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.
authors.affiliation: Division of Neonatology, Department of Pediatrics, Gulhane Military Medical Academy, Ankara, Turkey. drmerih@yahoo.com
authors.forename: Merih
authors.initials: M
authors.lastname: Cetinkaya
authors.forename: Mehmet
authors.initials: M
authors.lastname: Cansev
authors.forename: Ferhat
authors.initials: F
authors.lastname: Cekmez
authors.forename: Cuneyt
authors.initials: C
authors.lastname: Tayman
authors.forename: Fuat Emre
authors.initials: FE
authors.lastname: Canpolat
authors.forename: Ilker M
authors.initials: IM
authors.lastname: Kafa
authors.forename: Sema
authors.initials: S
authors.lastname: Uysal
authors.forename: Turan
authors.initials: T
authors.lastname: Tunc
authors.forename: S Umit
authors.initials: SU
authors.lastname: Sarici
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D020345:Enterocolitis, Necrotizing / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D007422:Intestines / Q000201:enzymology / Q000473:pathology; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats
chemical_list: D016207:Cytokines; D018697:Nootropic Agents; D003566:Cytidine Diphosphate Choline