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    標題: Melatonin reduces acute lung inflammation, edema, and hemorrhage in heatstroke rats
    作者: Wu, Wen-shiann
    Chou, Ming-ting
    Chao, Chien-ming
    Chang, Chen-kuei
    Lin, Mao-tsun
    Chang, Ching-ping
    貢獻者: 通識教育中心
    關鍵字: Free Radicals
    Heat Stroke
    Melatonin
    Acute Lung Injury
    Wistar Rats
    Tumor Necrosis Factor Alpha
    Interleukins
    Nitric Oxide
    日期: 2012-06
    上傳時間: 2014-03-21 16:16:01 (UTC+8)
    出版者: Acta Pharmacologica Sinica
    摘要: Aim: To assess the therapeutic effect of melatonin on heat-induced acute lung inflammation and injury in rats.Methods: Heatstroke was induced by exposing anesthetized rats to heat stress (36 degrees C, 100 min). Rats were treated with vehicle or melatonin (0.2, 1, 5 mg/kg) by intravenous administration 100 min after the initiatioin of heatstroke and were allowed to recover at room temperature (26 degrees C). The acute lung injury was quantified by morphological examination and by determination of the volume of pleural exudates, the number of polymorphonuclear (PMN) cells, and the myeloperoxidase (MPO) activity. The concentrations of tumor necrosis factor, interleukin (IL)-1 beta, IL-6, and IL-10 in bronchoalveolar fluid (BALF) were measured by ELISA. Nitric oxide (NO) level was determined by Griess method. The levels of glutamate and lactate-to-pyruvate ratio were analyzed by CMA600 microdialysis analyzer. The concentrations of hydroxyl radicals were measured by a procedure based on the hydroxylation of sodium salicylates leading to the production of 2,3-dihydroxybenzoic acid (DHBA).Results: Melatonin (1 and 5 mg/kg) significantly (i) prolonged the survival time of heartstroke rats (117 and 186 min vs 59 min); (ii) attenuated heatstroke-induced hyperthermia and hypotension; (iii) attenuated acute lung injury, including edema, neutrophil infiltration, and hemorrhage scores; (iv) down-regulated exudate volume, BALE PMN cell number, and MPO activity; (v) decreased the BALE levels of lung inflammation response cytokines like TNF-alpha, interleukin (IL)-1 beta, and IL-6 but further increased the level of an anti-inflammatory cytokine IL-10; (vi) reduced BALE levels of glutamate, lactate-to-pyruvate ratio, NO, 2,3-DHBA, and lactate dehydrogenase.Conclusion: Melatonin may improve the outcome of heatstroke in rats by attenuating acute lung inflammation and injury.
    關聯: Acta Pharmacologica Sinica v.33 n.6 pp.775-782
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