Cuneyt Tayman1, Salih Aydemir2, Ibrahim Yakut3, Utku Serkant4, Atilla Ciftci5, Erken Arslan6, Orhan Koç7. 1. a Department of Neonatology , Denizli Public Health Hospital , Denizli , Turkey. 2. b Department of Pediatrics , Dr. Sami Ulus Children and Research Hospital Hospital , Ankara , Turkey. 3. c Department of Pediatrics , Zekai Tahir Burak Maternity Education and Research Hospital , Ankara , Turkey. 4. d Department of Biochemistry , Golbası Public Health Hospital , Ankara , Turkey. 5. e Department of Pediatrics , Ankara Hematology Oncology Children Education and Research Hospital , Ankara , Turkey. 6. f Department of Urology , Afyon Public Health Hospital , Afyon , Turkey. 7. g Department of Pediatric Surgery , Etimesgut Public Health Hospital , Ankara , Turkey.
Abstract
OBJECTIVES: 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. MATERIAL AND 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). CONCLUSION: 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.
OBJECTIVES: 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. MATERIAL AND 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). CONCLUSION: 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: Victoria G Weis; Anna C Deal; Gehad Mekkey; Cara Clouse; Michaela Gaffley; Emily Whitaker; Cole B Peeler; Jared A Weis; Marshall Z Schwartz; Anthony Atala Journal: Am J Physiol Gastrointest Liver Physiol Date: 2021-02-10 Impact factor: 4.052