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    All-Trans-Retinoic Acid Attenuates Intestinal Injury in a Neonatal Rat Model of Necrotizing Enterocolitis
    (Karger, 2013) Ozdemir, Ramazan; Yurttutan, Sadik; Sari, Fatma Nur; Oncel, Mehmet Yekta; Erdeve, Omer; Unverdi, Hatice Germen; Uysal, Bulent
    Background: Ischemia/reperfusion-induced intestinal injury is mediated by reactive oxygen species and inflammatory mediators. Objectives: This study was designed to evaluate whether all-trans-retinoic acid (ATRA) administration can attenuate intestinal injury and to analyze the antioxidant and anti-inflammatory effects of ATRA in a neonatal rat model of necrotizing enterocolitis (NEC). Methods: Twenty-nine Wistar albino rat pups were randomly divided into 3 groups: group 1 = control, group 2 = NEC and saline, and group 3 = NEC and ATRA treatment. NEC was induced by hyperosmolar enteral formula feeding and exposure to hypoxia after cold stress at +4 degrees C and oxygen. Pups in group 3 were injected intraperitoneally with ATRA (0.5 mg/kg body weight) once a day prior to each NEC procedure, beginning on postnatal day 1 and daily through postnatal day 4. The pups were killed on the 4th day and their intestinal tissues were harvested for biochemical and histopathological analysis. Results: Mucosal injury scores and intestinal malondialdehyde levels in group 2 were found to be significantly higher than other groups (p < 0.05). Intestinal superoxide dismutase and glutathione peroxidase activities in group 3 were significantly higher than group 2 (p = 0.04 and p = 0.04, respectively). Intestinal tissue tumor necrosis factor-alpha levels were significantly reduced with ATRA treatment in group 3 compared to group 2 (p < 0.001). Conclusions: It is likely that oxidative stress and inflammatory mediators contributed to the pathogenesis of NEC and that ATRA had a protective effect on intestinal injury through its anti-inflammatory and antioxidant properties. Copyright (c) 2013 S. Karger AG, Basel
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    Beneficial effects of Etanercept on experimental necrotizing enterocolitis
    (Springer, 2014) Yurttutan, Sadik; Ozdemir, Ramazan; Canpolat, Fuat Emre; Oncel, Mehmet Yekta; Unverdi, Hatice Germen; Uysal, Bulent; Erdeve, Omer
    Tissue damage in necrotizing enterocolitis (NEC) of infants occurs as a result of an uncontrolled inflammatory response. The aim of this study was to investigate any potential anti-inflammatory effects that Etanercept may have on the inflammatory response in an experimental NEC model in newborn rats. Newborn pups were randomized into three groups immediately after birth (Control, NEC + Placebo and NEC + Etanercept). Pups in the NEC + Placebo and NEC + Etanercept groups were subjected to an NEC-inducing protocol (hypercarbia, hypothermia and hyperoxia) twice a day for 3 days. Pups in the NEC + Etanercept group were given an intraperitoneal injection of Etanercept. Rats were harvested for biochemical and histopathological examinations. The histopathological injury score of rats in the NEC + Placebo group was significantly higher compared to the NEC + Etanercept and Control groups (p < 0.05 for both comparisons). Tissue levels of tumor necrosis factor-alpha, interleukin-1 beta, and malondialdehyde were higher in the placebo group compared to the Etanercept group. Our results suggest that Etanercept attenuates intestinal tissue damage in NEC by reducing inflammation and blocking the production of free-oxygen radicals, while also reducing tissue levels of tumor necrosis factor-alpha and interleukin-1 beta.