Melatonin as a Promising Anti-Inflammatory Agent in an In Vivo Animal Model of Sepsis-Induced Rat Liver Damage

Author:

Benedeto-Stojanov Daniela1,Ničković Vanja P.2,Petrović Gordana1,Rancić Andrija3ORCID,Grgov Ivan4,Nikolić Gordana R.5,Marčetić Zoran P.5ORCID,Popović Milica R.6,Lazarević Milan7ORCID,Mitić Katarina V.8,Sokolović Dušan9ORCID

Affiliation:

1. Faculty of Medicine, University of Niš, 18000 Niš, Serbia

2. COVID Hospital Kruševac, University Clinical Centre of Niš, 37000 Kruševac, Serbia

3. Clinic of Gastroenterohepatology, University Clinical Centre of Niš, 18000 Niš, Serbia

4. General Hospital Leskovac, Department of General Surgery with Traumatology, 16000 Leskovac, Serbia

5. Faculty of Medicine, University of Priština, 38220 Kosovska Mitrovica, Serbia

6. Pediatrics Clinic, Clinical Centre Priština, 38205 Gracanica, Serbia

7. Clinic for Cardiovascular and Transplant Surgery, Faculty of Medicine, University Clinical Centre of Niš, 18000 Niš, Serbia

8. Institute of Physiology and Biochemistry “Ivan Djaja”, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia

9. Institute for Biochemistry, Faculty of Medicine, University of Niš, 18000 Niš, Serbia

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.

Funder

Ministry of Education, Science, and Technological Development of the Republic of Serbia

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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