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

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.

Effects of melatonin on low-dose lipopolysaccharide-induced oxidative stress in mouse liver, muscle, and kidney.

Lipopolysaccharide (LPS) administration in an in vivo experimental mice model causes oxidative damage in the liver, muscle, and kidney. We aimed to determine specific mechanisms underlying melatonin's antioxidant protective role. Assays were carried out in quadruplicate in the control, melatonin (10 mg/kg, 10 days), acute LPS administration (once 150 µg), and LPS + melatonin groups. LPS stimulated lipid peroxidation processes (dienes and malondialdehyde) and antioxidant enzyme concentrations (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) were assessed in all investigated tissues. Protein oxidation processes (measured as aldehyde and kenotic carbonyl protein derivatives) were enhanced by LPS in the kidney and liver but not in muscle. Melatonin reversed LPS-induced changes, with the exception of muscle protein oxidation. LPS-induced oxidative stress resulted in augmented early-stage diene conjugated and end-stage malondialdehyde lipid peroxidation processes and affected antioxidant activity in liver, kidney, and muscle tissues. LPS activated protein oxidation processes in the kidney and liver. Melatonin ameliorated oxidative damage in the liver, kidney, and partially in the muscle. Melatonin modulates oxidative stress-induced states. Potential synergism between melatonin and systemic inflammation in terms of oxidative modification of muscle proteins needs to be clarified in further studies.

Melatonin and Metformin Diminish Oxidative Stress in Heart Tissue in a Rat Model of High Fat Diet and Mammary Carcinogenesis.

The aim of this study was to determine the effects of long-term administration of the oral antidiabetic metformin or the pineal hormone melatonin, and a combination thereof, in preventing oxidative stress in the heart tissue of female Sprague-Dawley rats with mammary tumors induced by N-methyl-N-nitrosourea (NMU) (50 mg/kg) given on the 42nd postnatal day. Metformin and melatonin were administered 12 days before and 16 weeks after the carcinogen. During the experiment, all animals were fed a high fat diet (10% total fat, 2.5% from lard, and 7.5% from palm oil). The findings are that mammary carcinogenesis generated oxidative stress. Reactive oxygen species (ROS) content, estimated from thiobarbituric acid reactive substances (TBARS), oxidatively modified protein content (aldehyde and ketone derivatives), and the activity of the antioxidant enzymes superoxide dismutase, glutathione reductase, and glutathione peroxidase were all augmented. Metformin caused a decrease in oxidative stress in the heart, accompanied by a decrease in diene conjugates, the elimination of ROS (stable total antioxidant status), and the activation of catalase and glutathione reductase. Melatonin caused an increase in total antioxidant status and a substantial reduction in ROS as estimated from aldehyde and ketone derivatives, lipid peroxidation at the initial (diene conjugates) and terminal stages (TBARS), and increased catalase and glutathione peroxidase activities. Metformin and melatonin combined reversed the effects of NMU on oxidative stress. In conclusion, melatonin reduces the level of oxidative stress in the heart tissue, caused by NMU carcinogenesis and a high fat diet, significantly stronger than metformin.

Melatonin Restores White Blood Cell Count, Diminishes Glycated Haemoglobin Level and Prevents Liver, Kidney and Muscle Oxidative Stress in Mice Exposed to Acute Ethanol Intoxication.

AIMS: The aim of the study was to examine the effects of melatonin impact on changes in haematological profile, biomarkers of oxidative stress (dienes conjugates, malondialdehyde (MDA), oxidatively modified protein levels, total antioxidant capacity and antioxidant enzyme activity) in liver, muscle, kidney and erythrocytes, and glycated haemoglobin (HBA1c) in mice during acute ethanol stress. METHODS: Assays were carried out in quadruplicate: control, melatonin (10 mg/kg, 10 days), acute ethanol stress (0.75 g/kg/day, 10 days) and acute ethanol stress plus melatonin groups. RESULTS: Acute ethanol stress caused a significant increase in the total number of white blood cells (WBC), especially neutrophils in the blood, and HBA1c levels vs. control mice. The correlation between lipid peroxidation and the glycated haemoglobin level was shown (r = 0.93, P = 0.007). Ethanol reduced the antioxidant capacity by increasing reactive oxygen species (ROS) production and the level of oxidatively modified protein content, diene conjugates and MDA. Melatonin administration in animals during acute ethanol stress reduced antioxidant stress biomarkers, WBC, HBA1c levels and ROS production. CONCLUSIONS: Melatonin had protective effects on liver, kidney and muscle tissues by preventing the intensive lipid peroxidation processes in initial (diene conjugation production) and late stages (MDA level), and significantly reduced the level of aldehyde and ketone protein derivatives. Furthermore, melatonin restored elevated WBC count and HBA1c level and diminished ROS production. SHORT SUMMARY: Ethanol reduces antioxidant capacity and leads to exaggerated reactive oxygen species production and consequent increases in oxidatively modified proteins. Melatonin exerts protective effects by preventing the intensive lipid peroxidation processes. Melatonin significantly reduces the level of aldehyde and ketone protein derivatives, restores glycated haemoglobin level and white blood cell count.