TNF-α Blockade Efficiently Reduced Severe Intestinal Damage in Necrotizing Enterocolitis

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.

Keywords::

• necrotizing enterocolitis
• infliximab
• TNF-α
• protection
• treatment
• newborn
• rat