Mahdi Alamili1, Klaus Bendtzen2, Jens Lykkesfeldt3, Jacob Rosenberg4, Ismail Gögenur4. 1. Department of Surgical Gastroenterology, University of Copenhagen, Herlev Hospital, Denmark. Electronic address: mahdi_alamili@hotmail.com. 2. Institute for Inflammation Research, Department of Rheumatology, Copenhagen University Hospital, Rigshospitalet, Denmark. 3. Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. 4. Department of Surgical Gastroenterology, University of Copenhagen, Herlev Hospital, Denmark.
Abstract
PURPOSE:Melatonin used as an exogenous drug has been documented to have potent antioxidant and anti-inflammatory effects in animal model. We aimed to examine the effect of melatonin in an experimental human sepsis model. MATERIALS AND METHODS:Twelve healthy males were enrolled in a randomized, placebo-controlled, double-blinded cross-over trial. They received lipopolysaccharide endotoxin 0.3 ng/kg of body weight intravenously at 12:00. Before endotoxemia, an 8-hour infusion of melatonin (100 mg) or placebo (saline) was initiated. Blood samples were drawn before and at 2, 4, 6, and 8 hours after lipopolysaccharide administration. Proinflammatory (tumor necrosis factor α [TNF-α], interleukin [IL] 1β, IL-6, and YKL-40), anti-inflammatory markers (IL-1Ra, IL-10, soluble tumor necrosis factor receptor I, and soluble tumor necrosis factor receptor II), a marker for oxidative damage (malondialdehyde), and antioxidants (ascorbic acid and dehydroascorbic acid) were analyzed in plasma. RESULTS:Melatonin significantly reduced proinflammatory markers IL-1β (P < .01) and YKL-40 (P < .05) but not TNF-α and IL-6. None of the anti-inflammatory markers (IL-1Ra, IL-10, soluble tumor necrosis factor receptor I, and soluble tumor necrosis factor receptor II) were lowered by melatonin. Melatonin reduced the levels of ascorbic acid (P < .05) but not dehydroascorbic acid or malondialdehyde. CONCLUSIONS:Melatonin administration before endotoxemia resulted in reduction of certain markers of inflammation and oxidative stress. Further studies are needed to clarify the role of melatonin in clinical setting.
RCT Entities:
PURPOSE:Melatonin used as an exogenous drug has been documented to have potent antioxidant and anti-inflammatory effects in animal model. We aimed to examine the effect of melatonin in an experimental humansepsis model. MATERIALS AND METHODS: Twelve healthy males were enrolled in a randomized, placebo-controlled, double-blinded cross-over trial. They received lipopolysaccharide endotoxin 0.3 ng/kg of body weight intravenously at 12:00. Before endotoxemia, an 8-hour infusion of melatonin (100 mg) or placebo (saline) was initiated. Blood samples were drawn before and at 2, 4, 6, and 8 hours after lipopolysaccharide administration. Proinflammatory (tumor necrosis factor α [TNF-α], interleukin [IL] 1β, IL-6, and YKL-40), anti-inflammatory markers (IL-1Ra, IL-10, soluble tumor necrosis factor receptor I, and soluble tumor necrosis factor receptor II), a marker for oxidative damage (malondialdehyde), and antioxidants (ascorbic acid and dehydroascorbic acid) were analyzed in plasma. RESULTS:Melatonin significantly reduced proinflammatory markers IL-1β (P < .01) and YKL-40 (P < .05) but not TNF-α and IL-6. None of the anti-inflammatory markers (IL-1Ra, IL-10, soluble tumor necrosis factor receptor I, and soluble tumor necrosis factor receptor II) were lowered by melatonin. Melatonin reduced the levels of ascorbic acid (P < .05) but not dehydroascorbic acid or malondialdehyde. CONCLUSIONS:Melatonin administration before endotoxemia resulted in reduction of certain markers of inflammation and oxidative stress. Further studies are needed to clarify the role of melatonin in clinical setting.
Authors: Diana Maria Chitimus; Mihaela Roxana Popescu; Suzana Elena Voiculescu; Anca Maria Panaitescu; Bogdan Pavel; Leon Zagrean; Ana-Maria Zagrean Journal: Biomolecules Date: 2020-08-20
Authors: Helen F Galley; Damon A Lowes; Lee Allen; Gary Cameron; Lorna S Aucott; Nigel R Webster Journal: J Pineal Res Date: 2014-04-05 Impact factor: 13.007