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Therapeutic effects of melatonin on heatstroke-induced multiple organ dysfunction syndrome in rats.

Abstract
Melatonin reportedly exerts beneficial effects to attenuate multiple organ dysfunction syndrome (MODS) in septic shock. Heatstroke resembles septic shock in many aspects. Thus, this study was performed on the anesthetized rats by using heat exposure to induce heatstroke-associated MODS. We evaluated the effect of melatonin, a versatile molecule synthesized in the pineal gland and in many organs, in heatstroke rats and showed that melatonin (0.2-5.0 mg/kg of body weight, i.v., immediately after the start of heat stress) significantly (i) attenuated hyperthermia, hypotension and hypothalamic ischemia and hypoxia, (ii) reduced plasma index of the toxic oxidizing radicals like nitric oxide metabolites and hydroxyl radicals, (iii) diminished plasma index of hepatic and renal dysfunction like creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase, (iv) attenuated plasma systemic inflammation response molecules like soluble intercellular and lesion molecule-1, E-selectin, tumor necrosis factor-alpha, interleukin (IL)-1β, and IL-6, (v) promoted plasma levels of an anti-inflammatory cytokine IL-10, (vi) reduced an index of infiltration of polymorphonuclear neutrophils in the lung like myeloperoxidase activity, and (vii) promoted the survival time to fourfold compared with the heatstroke alone group. Thus, melatonin could be a novel agent for the treatment of heatstroke animals or patients in the early stage.
AuthorsXiao-Jing Lin, Gui-Ping Mei, Jian Liu, Yi-Lei Li, Dan Zuo, Shao-Jun Liu, Ting-Bao Zhao, Mao-Tsun Lin
JournalJournal of pineal research (J Pineal Res) Vol. 50 Issue 4 Pg. 436-44 (May 2011) ISSN: 1600-079X [Electronic] England
PMID21392091 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2011 John Wiley & Sons A/S.
Chemical References
  • Antioxidants
  • Interleukin-1beta
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Interleukin-10
  • Melatonin
Topics
  • Animals
  • Antioxidants (therapeutic use)
  • Heat Stroke (physiopathology)
  • Intercellular Adhesion Molecule-1 (blood)
  • Interleukin-10 (blood)
  • Interleukin-1beta (blood)
  • Interleukin-6 (blood)
  • Male
  • Melatonin (therapeutic use)
  • Multiple Organ Failure (drug therapy, etiology)
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha (blood)

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