Melatonin suppresses markers of inflammation and oxidative damage in a human daytime endotoxemia model

TY - JOUR

T1 - Melatonin suppresses markers of inflammation and oxidative damage in a human daytime endotoxemia model

AU - Alamili, Mahdi

AU - Bendtzen, Klaus

AU - Lykkesfeldt, Jens

AU - Rosenberg, Jacob

AU - Gögenür, Ismayil

N1 - © 2013.

PY - 2014/2

Y1 - 2014/2

N2 - 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] 1. β, 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.

AB - 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] 1. β, 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.

KW - Faculty of Health and Medical Sciences

KW - Melatonin

KW - Endotoxemia

KW - Human

KW - Sepsis

KW - Inflammation

KW - Oxidative stress

KW - Oxidative damage

U2 - 10.1016/j.jcrc.2013.09.006

DO - 10.1016/j.jcrc.2013.09.006

M3 - Journal article

C2 - 24140166

SN - 0883-9441

VL - 29

SP - 184.e9-184.e13

JO - Journal of Critical Care

JF - Journal of Critical Care

IS - 1

ER -