Melatonin does not affect disseminated intravascular coagulation but diminishes decreases in platelet count during subacute endotoxaemia in rats

Lansink, Maren Oude; Görlinger, Klaus; Hartmann, Matthias; Groot, Herbert de; Effenberger-Neidnicht, Katharina

doi:10.1016/j.thromres.2015.10.025

Cited by 12 publications

(9 citation statements)

References 43 publications

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“…To the best of our knowledge, we are the first to show that melatonin restores WBC in acute low-dose LPS toxicity. Although the beneficial effects of melatonin have been reported in at least five studies (Sewerynek et al 1996;Fjaerli et al 1999;Yerer et al 2004;Alamili et al 2013;Lansink et al 2016), the LPS doses administered in these studies were much higher, thus mimicking sepsis state. In our study low-dose LPS was administered to develop low grade inflammation and oxidative stress that are typically associated with obesity and diabetes mellitus.…”

Section: Discussionmentioning

confidence: 97%

Melatonin diminishes oxidative stress in plasma, retains erythrocyte resistance and restores white blood cell count after low-dose lipopolysaccharide exposure in mice

Kurhaluk

Зайцева²,

Sliuta³

et al. 2018

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The aim of the study was to elucidate the effects of melatonin administration (10 mg/kg, 10 days) in a model of inflammation and oxidative stress induced by low-dose bacterial lipopolysaccharide (LPS, once 150 μg). Assays were carried out in quadruplicate in the control, melatonin (10 mg/ kg, 10 days), acute LPS administration (once 150 μg) and LPS plus melatonin groups. Blood morphological examination was performed. Erythrocyte resistance to haemolytic agents, ceruloplasmin, diene conjugates, malondialdehyde, oxidatively modified protein concentrations, total antioxidant capacity and antioxidant enzyme activity in plasma were measured. LPS administration in mice resulted in white blood cell (WBC) depletion, erythrocyte cell membrane impairment and oxidative stress in plasma characterised by lipid and protein oxidative processes, decreased antioxidative defence and augmented ceruloplasmin concentrations. Melatonin treatment provided to LPS-exposed animals restored WBC counts, ameliorated erythrocyte membrane damage and decreased overall oxidative stress in plasma. Melatonin provides multilevel protection in animals exposed to low-dose LPS.

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Section: Discussionmentioning

confidence: 97%

Melatonin diminishes oxidative stress in plasma, retains erythrocyte resistance and restores white blood cell count after low-dose lipopolysaccharide exposure in mice

Kurhaluk

Зайцева²,

Sliuta³

et al. 2018

gpb

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“…Rats were anesthetized with isoflurane and received ketamine and lidocaine for analgesia as already described. 30 Afterwards, catheters were inserted in femoral artery and vein and perfused with Ringer’s solution to maintain the functionality of the catheters. At the end of the experiment, animals were sacrificed by cardiac incision under deep isoflurane anesthesia.…”

Section: Methodsmentioning

confidence: 99%

“…Systemic blood pressure, heart rates, and breathing rates were determined in 10 min intervals as already described. 30 Core temperature was kept constant above 37°C with an underlying heated operating table and by covering the rats with aluminum foil.…”

Section: Methodsmentioning

confidence: 99%

“…For each blood sampling, rats were substituted with 0.3 mL of Ringer’s solution. 30 At the end of the experiments (T = 300 min), final blood samples were taken in one-tenth volume of citrate (3.13%). Citrate blood plasma was used for thromboelastometry (ROTEM; TEM International, München, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…The kinetics of clot formation was analyzed by thromboelastometry using INTEM or EXTEM test and described in numerical parameters. 30 …”

Section: Methodsmentioning

confidence: 99%

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Moderate glucose supply reduces hemolysis during systemic inflammation

Jägers

Brauckmann

Kirsch

et al. 2018

JIR

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BackgroundSystemic inflammation alters energy metabolism. A sufficient glucose level, however, is most important for erythrocytes, since erythrocytes rely on glucose as sole source of energy. Damage to erythrocytes leads to hemolysis. Both disorders of glucose metabolism and hemolysis are associated with an increased risk of death. The objective of the study was to investigate the impact of intravenous glucose on hemolysis during systemic inflammation.Materials and methodsSystemic inflammation was accomplished in male Wistar rats by continuous lipopolysaccharide (LPS) infusion (1 mg LPS/kg and h, 300 min). Sham control group rats received Ringer’s solution. Glucose was supplied moderately (70 mg glucose/kg and h) or excessively (210 mg glucose/kg and h) during systemic inflammation. Vital parameters (eg, systemic blood pressure) as well as blood and plasma parameters (eg, concentrations of glucose, lactate and cell-free hemoglobin, and activity of lactate dehydrogenase) were measured hourly. Clot formation was analyzed by thromboelastometry.ResultsContinuous infusion of LPS led to a so-called post-aggression syndrome with disturbed electrolyte homeostasis (hypocalcemia, hyperkalemia, and hypernatremia), changes in hemodynamics (tachycardia and hypertension), and a catabolic metabolism (early hyperglycemia, late hypoglycemia, and lactate formation). It induced severe tissue injury (significant increases in plasma concentrations of transaminases and lactate dehydrogenase), alterations in blood coagulation (disturbed clot formation), and massive hemolysis. Both moderate and excessive glucose supply reduced LPS-induced increase in systemic blood pressure. Excessive but not moderate glucose supply increased blood glucose level and enhanced tissue injury. Glucose supply did not reduce LPS-induced alterations in coagulation, but significantly reduced hemolysis induced by LPS.ConclusionIntravenous glucose infusion can diminish LPS-related changes in hemodynamics, glucose metabolism, and, more interestingly, LPS-induced hemolysis. Since cell-free hemoglobin is known to be a predictor for patient’s survival, a reduction of hemolysis by 35% only by the addition of a small amount of glucose is another step to minimize mortality during systemic inflammation.

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

Brencher

Lansink

Effenberger-Neidnicht

2017

Inflammation

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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.

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Melatonin does not affect disseminated intravascular coagulation but diminishes decreases in platelet count during subacute endotoxaemia in rats

Cited by 12 publications

References 43 publications

Melatonin diminishes oxidative stress in plasma, retains erythrocyte resistance and restores white blood cell count after low-dose lipopolysaccharide exposure in mice

Melatonin diminishes oxidative stress in plasma, retains erythrocyte resistance and restores white blood cell count after low-dose lipopolysaccharide exposure in mice

Moderate glucose supply reduces hemolysis during systemic inflammation

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

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