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    Does leflunomide attenuate the sepsis-induced acute lung injury?
    (Springer, 2008) Ozturk, Erdogan; Demirbilek, Semra; Begec, Zekine; Surucu, Murat; Fadillioglu, Ersin; Kirimhoglu, Hale; Ersoy, M. Ozcan
    The organ that is affected first and most severely in intraabdominal sepsis is the lung. Oxygen radicals and active neutrophils in the lung are important sources for severe pulmonary inflammation leading to acute lung injury (ALI)/acute respiratory distress syndrome. The aim of this study was to investigate the effects of leflunomide, an immunomodulatory agent, on oxidant/antioxidant status with nitric oxide (NO) level and myeloperoxidase (MPO) activity in rats with sepsis-induced ALI. Fifty male Wistar albino rats were divided into five groups: control, sham, sepsis, leflunomide (10 mg/kg, intragastrically for two doses with an 8 h interval prior to the experiment) and sepsis + leflunomide. After the animals were anesthetized with ketamine and xylazine, the abdominal cavity was opened and ligated just below the ileocaecal valve with 3-0 silk. The antimesentric surface of the cecum was perforated and the cecum was gently compressed until fecal matter was extruded to induce sepsis. None of the rats received antibiotics during the experimental procedures. The experiment was ended 24 h after cecal ligation puncture (CLP) with the cervical dislocation under anesthesia. The lung tissues were removed for analysis of biochemical parameters and light microscopic investigation. The lung superoxide dismutase (SOD), catalase and glutathione peroxidase activities were decreased in the sepsis group as compared to the group control, sham, leflunomide and sepsis + leflunomide (P < 0.05), and SOD activity were significantly higher in group sepsis + leflunomide than sham, control, leflunomide and sepsis group (P < 0.05). The lung MPO, malondialdehyde (MDA), protein carbonyl and NO levels were higher in the sepsis group when compared to group control, sham, leflunomide and sepsis + leflunomide (P < 0.05), and MPO, MDA and NO levels were higher in the sepsis + leflunomide group than in the sham, control and leflunomide group (P < 0.05). The light microscopic evaluation showed that pulmonary architecture was preserved, and infiltration of neutrophil and edema decreased in sepsis + leflunomide group. The grade of alveolar damage was significantly decreased in sepsis + leflunomide group in comparison with sepsis group (P < 0.05). Our findings suggested that leflunomide attenuated the lung injury after CLP-induced sepsis by inhibition of neutrophils accumulation and increasing endogenous antioxidant capacity.
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    Protective effect of leflunomide against oxidative intestinal injury in a rodent model of sepsis
    (Academic Press Inc Elsevier Science, 2014) Ozturk, Erdogan; Surucu, Murat; Karaman, Abdurrahman; Samdanci, Emine; Fadillioglu, Ersin
    Background: Sepsis is defined as an uncontrolled inflammatory response in a host. The process may lead to severe sepsis, multisystem organ failure and even death. Leflunomide has important immunomodulatory and anti-inflammatory effects, which may mitigate host response to bacterial translocation. The goal of our study was to measure the effects leflunomide administration had on a variety of biochemical markers upregulated in systemic inflammatory response syndrome, sepsis, and multiple organ failure syndrome. Materials and methods: Wistar albino type rats were randomly divided into five groups: control, sham, leflunomide, sepsis, and sepsis + leflunomide. Sepsis was achieved by means of the cecal ligation and puncture method. Leflunomide 2 x 10 mg/kg/d was administered before the experiment. At the end of 24 h, the tissue levels of superoxide dismutase, catalase activity, malondialdehyde, nitric oxide, and protein carbonyl were measured. Results: The level of the bowel superoxide dismutase and catalase levels of the sepsis group is significantly lower than those of the control, sham, and leflunomide groups (P < 0.05). Malondialdehyde, nitric oxide, and protein carbonyl levels are significantly higher in sepsis compared with other groups (P < 0.05). Conclusions: Leflunomide's prevention of protein and lipid peroxidation was observed in septic bowel tissue. Use of leflunomide could have protective effects against both the onset and the progressive stages of sepsis. Crown Copyright (c) 2014 Published by Elsevier Inc. All rights reserved.