title: TNF-α Blockade Efficiently Reduced Severe Intestinal Damage in Necrotizing Enterocolitis.
abstract: OBJECTIVE
  To ascertain the beneficial effects of infliximab an inhibitor of tumor necrosis factor alpha (TNF-α) on the development of NEC in an experimental NEC rat model.
  
  
  METHODS
  Thirty newborn Sprague-Dawley rats were randomly divided into three groups as NEC, NEC+ infliximab, and control. NEC was induced by enteral formula feeding, exposure to hypoxia-hyperoxia and cold stress. Pups in the NEC+ infliximab group were administered infliximab at a dose of 10 mg/kg daily by intraperitoneal route from the first day until the end of the study. All pups were sacrificed on the 5th day. Proximal colon and ileum were excised for histopathologic, immunohistochemical (TUNEL and caspase-3), and biochemical evaluation, including, total antioxidant status (TAS), total oxidant status (TOS), malonaldehyde (MDA), and myeloperoxdase (MPO) and TNF-α activities.
  
  
  RESULTS
  We observed better clinical sickness scores, weight gain, and survival rate in the NEC+ infliximab group compared to the NEC group (p < .05). Histopathological and apoptosis examination (TUNEL and immunohistochemical evaluation for caspase-3) revealed lower damage in the NEC+ infliximab group compared to the damage in the NEC group (p < .01). Tissue MDA, MPO, TNF-α levels, and TOS were significantly decreased in the NEC+infliximab group, whereas TAS was significantly increased in the NEC + infliximab group (p < .01).
  
  
  CONCLUSIONS
  TNF-α blockade with infliximab efficiently reduced the intestinal injury and preserve the intestinal tissues from severe intestinal damage by its complex mechanisms on NEC. Therefore, it may be an alternative option for the treatment of NEC.
authors.affiliation: a Department of Neonatology , Denizli Public Health Hospital , Denizli , Turkey.
authors.forename: Cuneyt
authors.initials: C
authors.lastname: Tayman
authors.affiliation: b Department of Pediatrics , Dr. Sami Ulus Children and Research Hospital Hospital , Ankara , Turkey.
authors.forename: Salih
authors.initials: S
authors.lastname: Aydemir
authors.affiliation: c Department of Pediatrics , Zekai Tahir Burak Maternity Education and Research Hospital , Ankara , Turkey.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yakut
authors.affiliation: d Department of Biochemistry , Golbası Public Health Hospital , Ankara , Turkey.
authors.forename: Utku
authors.initials: U
authors.lastname: Serkant
authors.affiliation: e Department of Pediatrics , Ankara Hematology Oncology Children Education and Research Hospital , Ankara , Turkey.
authors.forename: Atilla
authors.initials: A
authors.lastname: Ciftci
authors.affiliation: f Department of Urology , Afyon Public Health Hospital , Afyon , Turkey.
authors.forename: Erken
authors.initials: E
authors.lastname: Arslan
authors.affiliation: g Department of Pediatric Surgery , Etimesgut Public Health Hospital , Ankara , Turkey.
authors.forename: Orhan
authors.initials: O
authors.lastname: Koç
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020287:In Situ Nick-End Labeling; D000069285:Infliximab / Q000008:administration & dosage / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005765:Gastrointestinal Agents; D016877:Oxidants; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab
keywords: TNF-α; infliximab; necrotizing enterocolitis; newborn; protection; rat; treatment