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Leukotriene receptor blocker montelukast protects against burn-induced oxidative injury of the skin and remote organs
Authors:Sener Göksel  Kabasakal Levent  Cetinel Sule  Contuk Gazi  Gedik Nursal  Yeğen Berrak C
Institution:1. School of Pharmacy, Department of Pharmacology, Marmara University, 34668 Haydarpaşa, Istanbul, Turkey;2. School of Medicine, Departments of Histology and Embryology, Marmara University, 34668 Haydarpaşa, Istanbul, Turkey;3. School of Medicine, Department of Physiology, Marmara University, 34668 Haydarpaşa, Istanbul, Turkey;4. Kasımpasa Military Hospital, Division of Biochemistry, Istanbul, Turkey;1. Department of Surgery, University of California, Irvine, Irvine, CA;2. Department of Statistics, University of California, Irvine, Irvine, CA;1. Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, via Regina Elena 299, 00161 Roma, Italy;2. Department of Pharmacy and Biotechnology, University of Bologna, via Irnerio 48, 40126 Bologna, Italy;1. Division of Urology, Department of Surgery, Duke University Medical Center, Durham, NC, USA;2. Division of Animal Laboratory Resources, Duke University Medical Center, Durham, NC, USA;3. Department of Pathology, Duke University Medical Center, Durham, NC, USA;4. Department of Urology, Children''s National Medical Center, Washington, DC, USA;1. Student Research Committee, Shoushtar University of Medical Sciences, Shoushtar, Iran;2. Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;3. Department of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;4. Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;5. Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;1. Rare Sugar Research Center, Kagawa University, Miki-cho, Kagawa 761-0795, Japan;2. Faculty of Agriculture, Kagawa University, Miki-cho, Kagawa 761-0795, Japan
Abstract:Thermal injury elicits several systemic consequences, among them the systemic inflammatory response where the generation of reactive oxygen radicals and lipid peroxidation play important roles. In the present study, we investigated whether the leukotriene receptor blocker montelukast is protective against burn-induced remote organ injury. Under brief ether anaesthesia, shaved dorsum of the rats was exposed to 90 degrees C (burn group) or 25 degrees C (control group) water bath for 10 s. Montelukast (10 mg/kg) or saline was administered intraperitoneally immediately after and at the 12th hour of the burn injury. Rats were decapitated 24 h after burn injury and the tissue samples from lung, liver, kidney and skin were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Tissues were also examined microscopically. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and creatinine, urea (BUN) concentrations were determined to assess liver and kidney function, respectively. Tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) were also assayed in serum samples. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, which was accompanied with significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, serum ALT, AST and BUN levels, as well as LDH and TNF-alpha, were elevated in the burn group as compared to control group. On the other hand, montelukast treatment reversed all these biochemical indices, as well as histopathological alterations, which were induced by thermal trauma. Findings of the present study suggest that montelukast possesses an anti-inflammatory effect on burn-induced damage in remote organs and protects against oxidative organ damage by a neutrophil-dependent mechanism.
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