Protective Effects of Ramelteon on Acute Lung Injury in Endotoxin-Induced Sepsis in Rats

INTRODUCTION: Sepsis is a life-threatening excessive systemic inflammatory reaction syndrome to infection that usually occurs in patients with bacteremia. The respiratory system is one of the structures most affected by acute organ damage. Melatonin plays an important role in regulating various phys...

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Main Authors: Tuğba Nurcan Yüksel, Duygu Kose, Muhammet Ali Gürbüz, Zekai Halici, Fadime Canbolat, Esra Bozgeyik
Format: Article
Language:English
Published: Van Yuzuncu Yil University, School of Medicine 2023-04-01
Series:Van Tıp Dergisi
Subjects:
Online Access:https://jag.journalagent.com/z4/download_fulltext.asp?pdir=vtd&un=VTD-62582
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author Tuğba Nurcan Yüksel
Duygu Kose
Muhammet Ali Gürbüz
Zekai Halici
Fadime Canbolat
Esra Bozgeyik
author_facet Tuğba Nurcan Yüksel
Duygu Kose
Muhammet Ali Gürbüz
Zekai Halici
Fadime Canbolat
Esra Bozgeyik
author_sort Tuğba Nurcan Yüksel
collection DOAJ
description INTRODUCTION: Sepsis is a life-threatening excessive systemic inflammatory reaction syndrome to infection that usually occurs in patients with bacteremia. The respiratory system is one of the structures most affected by acute organ damage. Melatonin plays an important role in regulating various physiological functions of the body, including antioxidant and anti-inflammatory. Ramelteon (RAME) is the first melatonin receptor agonist confirmed for clinical use. The goal of this study is to determine the effects of RAME on endotoxin-induced septic lung injury in rats. METHODS: Thirty-two female rats were separated randomly into four groups (n=8). Group healthy received intraperitoneal normal saline, group sepsis received intraperitoneally 10 mg/kg lipopolysaccharide (LPS), group sepsis+RAME2 received 10 mg/kg LPS plus 2mg/kg RAME, and group sepsis+RAME4 received 10 mg/kg LPS plus 4mg/kg RAME. RAME was administered by oral gavage 1 hour before LPS administration. The lung tissues were collected 12 hours after LPS administration and investigated molecularly (qRT-PCR analyses of Tumor Necrosis Factor-α, nuclear factor kappa-β, and interleukin 1-beta mRNA expression) and histopathologically (staining with Harris Hematoxylin and Eosin Y). RESULTS: TNF-α, NF-κβ, and IL-1β levels significantly decreased dose-dependent in the septic rats following RAME administration. RAME administration ameliorated histopathological injury in lung tissues due to sepsis. DISCUSSION AND CONCLUSION: RAME ameliorated the inflammatory response in endotoxin-induced sepsis. These findings suggest that RAME can be a promising agent by contributing to alternative preventive treatment methods for sepsis with its anti-inflammatory effect.
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spelling doaj.art-f13bdc80adcf467a9ab15cb31dabf26a2023-12-02T10:14:39ZengVan Yuzuncu Yil University, School of MedicineVan Tıp Dergisi2587-03512023-04-0130217818310.5505/vtd.2023.62582VTD-62582Protective Effects of Ramelteon on Acute Lung Injury in Endotoxin-Induced Sepsis in RatsTuğba Nurcan Yüksel0Duygu Kose1Muhammet Ali Gürbüz2Zekai Halici3Fadime Canbolat4Esra Bozgeyik5Department of Pharmacology, Faculty of Medicine, Tekirdag Namık Kemal University, Tekirdag, TurkeyDepartment of Pharmacology, Faculty of Medicine, Sutcu Imam University, Kahramanmaraş, TurkeyDepartment of Histology and Embryology, Medical Faculty, Ataturk University, Erzurum, TurkeyDepartment of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, TurkeyDepartment of Pharmacy Services, Vocational School of Health Services, Çanakkale Onsekiz Mart University, Çanakkale, TurkeyDepartment of Medical Services and Techniques, Vocational School of Health Services, Adıyaman University, Adıyaman, TurkeyINTRODUCTION: Sepsis is a life-threatening excessive systemic inflammatory reaction syndrome to infection that usually occurs in patients with bacteremia. The respiratory system is one of the structures most affected by acute organ damage. Melatonin plays an important role in regulating various physiological functions of the body, including antioxidant and anti-inflammatory. Ramelteon (RAME) is the first melatonin receptor agonist confirmed for clinical use. The goal of this study is to determine the effects of RAME on endotoxin-induced septic lung injury in rats. METHODS: Thirty-two female rats were separated randomly into four groups (n=8). Group healthy received intraperitoneal normal saline, group sepsis received intraperitoneally 10 mg/kg lipopolysaccharide (LPS), group sepsis+RAME2 received 10 mg/kg LPS plus 2mg/kg RAME, and group sepsis+RAME4 received 10 mg/kg LPS plus 4mg/kg RAME. RAME was administered by oral gavage 1 hour before LPS administration. The lung tissues were collected 12 hours after LPS administration and investigated molecularly (qRT-PCR analyses of Tumor Necrosis Factor-α, nuclear factor kappa-β, and interleukin 1-beta mRNA expression) and histopathologically (staining with Harris Hematoxylin and Eosin Y). RESULTS: TNF-α, NF-κβ, and IL-1β levels significantly decreased dose-dependent in the septic rats following RAME administration. RAME administration ameliorated histopathological injury in lung tissues due to sepsis. DISCUSSION AND CONCLUSION: RAME ameliorated the inflammatory response in endotoxin-induced sepsis. These findings suggest that RAME can be a promising agent by contributing to alternative preventive treatment methods for sepsis with its anti-inflammatory effect.https://jag.journalagent.com/z4/download_fulltext.asp?pdir=vtd&un=VTD-62582antiinflammatorylipopolysaccharidemelatoninramelteonsepsis
spellingShingle Tuğba Nurcan Yüksel
Duygu Kose
Muhammet Ali Gürbüz
Zekai Halici
Fadime Canbolat
Esra Bozgeyik
Protective Effects of Ramelteon on Acute Lung Injury in Endotoxin-Induced Sepsis in Rats
Van Tıp Dergisi
antiinflammatory
lipopolysaccharide
melatonin
ramelteon
sepsis
title Protective Effects of Ramelteon on Acute Lung Injury in Endotoxin-Induced Sepsis in Rats
title_full Protective Effects of Ramelteon on Acute Lung Injury in Endotoxin-Induced Sepsis in Rats
title_fullStr Protective Effects of Ramelteon on Acute Lung Injury in Endotoxin-Induced Sepsis in Rats
title_full_unstemmed Protective Effects of Ramelteon on Acute Lung Injury in Endotoxin-Induced Sepsis in Rats
title_short Protective Effects of Ramelteon on Acute Lung Injury in Endotoxin-Induced Sepsis in Rats
title_sort protective effects of ramelteon on acute lung injury in endotoxin induced sepsis in rats
topic antiinflammatory
lipopolysaccharide
melatonin
ramelteon
sepsis
url https://jag.journalagent.com/z4/download_fulltext.asp?pdir=vtd&un=VTD-62582
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