Melatonin as a potential therapy for sepsis: a phase I dose escalation study and an ex vivo whole blood model under conditions of sepsis.
Bottom Line: No adverse effects after oral melatonin, other than mild transient drowsiness with no effects on sleeping patterns, were seen, and no symptoms were reported.For the ex vivo study, blood from 20 volunteers was treated with lipopolysaccharide and peptidoglycan plus a range of concentrations of melatonin/6-hydroxymelatonin.Both melatonin and 6-hydroxymelatonin had beneficial effects on sepsis-induced mitochondrial dysfunction, oxidative stress, and cytokine responses at concentrations similar to those achieved in vivo.
Affiliation: Division of Applied Health, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK; Intensive Care Unit, Aberdeen Royal Infirmary, Aberdeen, UK.Show MeSH
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Mentions: In the ex vivo study, IL-6 and IL-10 were both significantly increased in plasma from blood exposed to LPS/PepG (both P < 0.0001, Fig.4) compared with solvent control. Exposure of blood to LPS/PepG plus melatonin or 6-hydroxymelatonin caused a significant dose-dependent decrease in IL-6 (Fig.4A), but IL-10 was unaffected by either drug (Fig.4B). Likewise, LPO was significantly higher in blood exposed to LPS/PepG, and both melatonin and 6-hydroxymelatonin caused a significant dose-dependent decrease (Fig.4C). The respiratory burst also increased upon exposure to LPS/PepG, and this was significantly decreased when blood was co-treated with LPS/PepG plus melatonin or 6-hydroxymelatonin (Fig.5).
Affiliation: Division of Applied Health, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK; Intensive Care Unit, Aberdeen Royal Infirmary, Aberdeen, UK.