Administration of Exogenous Melatonin After the Onset of Systemic Inflammation Is Hardly Beneficial

Abstract

Melatonin improves survival and functional impairment including hemolysis, thrombocytopenia, and hypotension when administered in a prophylactic manner or early after initiation of sepsis or endotoxemia. In the present study, melatonin was given not before first symptoms of systemic inflammation became manifest. Lipopolysaccharide was infused at a rate of 0.5 mg/kg × h to induce systemic inflammation in male Wistar rats. Melatonin (single dose 3 mg/kg × 15 min) was intravenously administered 180 and 270 min after starting of the lipopolysaccharide infusion. Systemic and vital parameters (e.g., systemic blood pressure and breathing rate) as well as blood and plasma parameters (acid-base parameters; electrolytes; parameters of tissue injury such as glucose concentration, lactate concentration, hemolysis, and aminotransferase activities; parameters of thromboelastometry; and platelet count) were determined in regular intervals. Infusion of lipopolysaccharide led to characteristic symptoms of severe systemic inflammation including hypotension, metabolic acidosis and hypoglycemia, electrolyte and hemostatic disturbances, thrombocytopenia, and hemolysis. Melatonin neither decreased mortality nor reduced lipopolysaccharide-dependent changes to vital, blood, and plasma parameters. Even though melatonin may have a beneficial effect in early stages of systemic inflammation, it can hardly be an option in therapy of manifest sepsis or endotoxemia in an intensive care unit.

Prophylactic supplement with melatonin successfully suppresses the pathogenesis of periodontitis through normalizing RANKL/OPG ratio and depressing the TLR4/MyD88 signaling pathway

“…In accordance with our findings, prophylactic treatment with melatonin has been reported to depress the TLR4/MyD88 pathway and protect neurons from focal cerebral ischemia or chloranil‐induced inflammation injury . Furthermore, pharmacological evidence also indicated that melatonin is highly efficient in minimizing tissue damage and preventing systemic inflammation only when administered in a prophylactic manner or soon after the injury . As the efficacy of prophylactic melatonin treatment is more evident than that of treatment after the induction of PD, the present study not only highlights the functional roles of melatonin in the treatment of PD, but also provides a critical insight for clinical use of melatonin as a preventive strategy to effectively repress PD‐induced destructive injury.…”

Protective Effect of Melatonin Against Polymicrobial Sepsis Is Mediated by the Anti-bacterial Effect of Neutrophils

“…Melatonin has been shown to have beneficial effects in the treatment of sepsis and inflammation (22, 23, 30, 43, 44). Treatment with melatonin contributed to the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) pathway, which are essential components of inflammasomes (45).…”

Moderate glucose supply reduces hemolysis during systemic inflammation

“… 9 – 12 The experimental model of continuous LPS infusion used in the present study reflects most pathophysiological changes known from clinical severe sepsis. 30 , 33 , 34 So, continuous infusion of LPS in our model led to an early hyperglycemic pre-shock state followed by a later hypoglycemic shock state. It induced severe functional impairment and tissue injury.…”