title: Melatonin reduces acute lung inflammation, edema, and hemorrhage in heatstroke rats.
abstract: OBJECTIVE
  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 °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 °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)-1β, 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, BALF PMN cell number, and MPO activity; (v) decreased the BALF levels of lung inflammation response cytokines like TNF-alpha, interleukin (IL)-1β, and IL-6 but further increased the level of an anti-inflammatory cytokine IL-10; (vi) reduced BALF levels of glutamate, lactate-to-pyruvate ratio, NO, 2,3-DHBA, and lactate dehydrogenase.
  
  
  CONCLUSIONS
  Melatonin may improve the outcome of heatstroke in rats by attenuating acute lung inflammation and injury.
authors.affiliation: Department of Cardiology, Chi Mei Medical Center, Chia Nan University of Pharmacy & Science, Tainan, Taiwan, China.
authors.forename: Wen-shiann
authors.initials: WS
authors.lastname: Wu
authors.forename: Ming-ting
authors.initials: MT
authors.lastname: Chou
authors.forename: Chien-ming
authors.initials: CM
authors.lastname: Chao
authors.forename: Chen-kuei
authors.initials: CK
authors.lastname: Chang
authors.forename: Mao-tsun
authors.initials: MT
authors.lastname: Lin
authors.forename: Ching-ping
authors.initials: CP
authors.lastname: Chang
mesh_terms: D055371:Acute Lung Injury / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D005334:Fever / Q000150:complications / Q000188:drug therapy; D018883:Heat Stroke / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006470:Hemorrhage / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D007022:Hypotension / Q000150:complications / Q000188:drug therapy; D016753:Interleukin-10 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000276:immunology; D011654:Pulmonary Edema / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000975:Antioxidants; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D008550:Melatonin