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1.
Int J Mol Sci ; 25(1)2023 Dec 29.
Article in English | MEDLINE | ID: mdl-38203627

ABSTRACT

Melatonin (MLT), earlier described as an effective anti-inflammatory agent, could be a beneficial adjunctive drug for sepsis treatment. This study aimed to determine the effects of MLT application in lipopolysaccharide (LPS)-induced sepsis in Wistar rats by determining the levels of liver tissue pro-inflammatory cytokines (TNF-α, IL-6) and NF-κB as well as hematological parameters indicating the state of sepsis. Additionally, an immunohistological analysis of CD14 molecule expression was conducted. Our research demonstrated that treatment with MLT prevented an LPS-induced increase in pro-inflammatory cytokines TNF-α and IL-6 and NF-κB levels, and in the neutrophil to lymphocyte ratio (NLR). On the other hand, MLT prevented a decrease in the blood lymphocyte number induced by LPS administration. Also, treatment with MLT decreased the liver tissue expression of the CD14 molecule observed after sepsis induction. In summary, in rats with LPS-induced sepsis, MLT was shown to be a significant anti-inflammatory agent with the potential to change the liver's immunological marker expression, thus ameliorating liver function.


Subject(s)
Melatonin , Sepsis , Rats , Animals , Rats, Wistar , Melatonin/pharmacology , Melatonin/therapeutic use , Interleukin-6 , Lipopolysaccharides/toxicity , NF-kappa B , Tumor Necrosis Factor-alpha/genetics , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Liver , Sepsis/complications , Sepsis/drug therapy , Cytokines , Lipopolysaccharide Receptors , Models, Animal
2.
Can J Physiol Pharmacol ; 99(4): 360-367, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32758112

ABSTRACT

The present study was designed to evaluate the cardioprotective effects of melatonin (a single dose of 50 mg·kg-1), a naturally occurring polypharmacological molecule, in Wistar rats acutely exposed to carbon tetrachloride (CCl4). This was done for the first time by tracking different biochemical parameters that reflect rat heart antioxidative and oxidative capacities, nitric oxide and arginine metabolism, and the glutathione cycle. Additionally, the extrinsic apoptosis pathway related parameters were studied. Acute exposure to CCl4 led to an increase in the studied tissue oxidant parameters (hydrogen peroxide, malondialdehyde, and carbonylated protein content), as well as the activity alteration of antioxidant (catalase, superoxide dismutase, and peroxidase) and glutathione-metabolizing (glutathione peroxidase, S-transferase, and reductase) enzymes. Furthermore, CCl4 caused a disturbance in the tissue myeloperoxidase, nitric oxide, citrulline, arginase, and inducible nitric oxide synthase content and activities and in two apoptosis-related parameters, caspase-3 and FAS ligand. Melatonin as a post-treatment prevented the changes induced by CCl4 to a differing extent, and in some cases, it was so potent that it completely abolished any tissue disturbances. This study is a promising starting point for further research directed to the development of melatonin treatment in cardiac tissue associated diseases.


Subject(s)
Arginine/metabolism , Carbon Tetrachloride/adverse effects , Glutathione/metabolism , Melatonin/pharmacology , Myocardium/metabolism , Nitric Oxide/metabolism , Oxidative Stress/drug effects , Animals , Antioxidants/metabolism , Catalase/metabolism , Glutathione Peroxidase/metabolism , Lipid Peroxidation/drug effects , Male , Malondialdehyde/metabolism , Myocardium/pathology , Rats , Rats, Wistar
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