The β1 Adrenergic Blocker Nebivolol Ameliorates Development of Endotoxic Acute Lung Injury

Acute lung injury (ALI) is a disease, with no effective treatment, which might result in death. Formations of excessive inflammation and oxidative stress are responsible for the pathophysiology of ALI. Nebivolol (NBL), a third-generation selective β1 adrenoceptor antagonist, has protective pharmacol...

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Main Authors: Esra Nurlu Temel, Mehtap Savran, Yalcın Erzurumlu, Nursel Hasseyid, Halil Ibrahim Buyukbayram, Gozde Okuyucu, Mehmet Abdulkadir Sevuk, Ozlem Ozmen, Ayse Coskun Beyan
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Journal of Clinical Medicine
Subjects:
Online Access:https://www.mdpi.com/2077-0383/12/5/1721
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author Esra Nurlu Temel
Mehtap Savran
Yalcın Erzurumlu
Nursel Hasseyid
Halil Ibrahim Buyukbayram
Gozde Okuyucu
Mehmet Abdulkadir Sevuk
Ozlem Ozmen
Ayse Coskun Beyan
author_facet Esra Nurlu Temel
Mehtap Savran
Yalcın Erzurumlu
Nursel Hasseyid
Halil Ibrahim Buyukbayram
Gozde Okuyucu
Mehmet Abdulkadir Sevuk
Ozlem Ozmen
Ayse Coskun Beyan
author_sort Esra Nurlu Temel
collection DOAJ
description Acute lung injury (ALI) is a disease, with no effective treatment, which might result in death. Formations of excessive inflammation and oxidative stress are responsible for the pathophysiology of ALI. Nebivolol (NBL), a third-generation selective β1 adrenoceptor antagonist, has protective pharmacological properties, such as anti-inflammatory, anti-apoptotic, and antioxidant functions. Consequently, we sought to assess the efficacy of NBL on a lipopolysaccharide (LPS)-induced ALI model via intercellular adhesion molecule-1 (ICAM-1) expression and the tissue inhibitor of metalloproteinases-1 (TIMP-1)/matrix metalloproteinases-2 (MMP-2) signaling. Thirty-two rats were split into four categories: control, LPS (5 mg/kg, intraperitoneally [IP], single dose), LPS (5 mg/kg, IP, one dosage 30 min after last NBL treatment), + NBL (10 mg/kg oral gavage for three days), and NBL (10 mg/kg oral gavage for three days). Six hours after the administration of LPS, the lung tissues of the rats were removed for histopathological, biochemical, gene expression, and immunohistochemical analyses. Oxidative stress markers such as total oxidant status and oxidative stress index levels, leukocyte transendothelial migration markers such as MMP-2, TIMP-1, and ICAM-1 expressions in the case of inflammation, and caspase-3 as an apoptotic marker, significantly increased in the LPS group. NBL therapy reversed all these changes. The results of this study suggest that NBL has utility as a potential therapeutic agent to dampen inflammation in other lung and tissue injury models
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spelling doaj.art-51f1fae338ed464ebbbb74b173e924d72023-11-17T07:57:27ZengMDPI AGJournal of Clinical Medicine2077-03832023-02-01125172110.3390/jcm12051721The β1 Adrenergic Blocker Nebivolol Ameliorates Development of Endotoxic Acute Lung InjuryEsra Nurlu Temel0Mehtap Savran1Yalcın Erzurumlu2Nursel Hasseyid3Halil Ibrahim Buyukbayram4Gozde Okuyucu5Mehmet Abdulkadir Sevuk6Ozlem Ozmen7Ayse Coskun Beyan8Department of Infectious Diseases, Faculty of Medicine, Suleyman Demirel University, 32260 Isparta, TurkeyDepartment of Pharmacology, Faculty of Medicine, Suleyman Demirel University, 32260 Isparta, TurkeyDepartment of Biochemistry, Faculty of Pharmacy, Suleyman Demirel University, 32260 Isparta, TurkeyDepartment of Pharmacology, Faculty of Medicine, Suleyman Demirel University, 32260 Isparta, TurkeyDepartment of Medical Biochemistry, Faculty of Medicine, Suleyman Demirel University, 32260 Isparta, TurkeyDepartment of Pathology, Faculty of Veterinary Medicine, Burdur Mehmet Akif Ersoy University, 15030 Burdur, TurkeyDepartment of Pharmacology, Faculty of Medicine, Suleyman Demirel University, 32260 Isparta, TurkeyDepartment of Pathology, Faculty of Veterinary Medicine, Burdur Mehmet Akif Ersoy University, 15030 Burdur, TurkeyDepartment of Occupational Medicine, Faculty of Medicine, Dokuz Eylul University, 35220 İzmir, TurkeyAcute lung injury (ALI) is a disease, with no effective treatment, which might result in death. Formations of excessive inflammation and oxidative stress are responsible for the pathophysiology of ALI. Nebivolol (NBL), a third-generation selective β1 adrenoceptor antagonist, has protective pharmacological properties, such as anti-inflammatory, anti-apoptotic, and antioxidant functions. Consequently, we sought to assess the efficacy of NBL on a lipopolysaccharide (LPS)-induced ALI model via intercellular adhesion molecule-1 (ICAM-1) expression and the tissue inhibitor of metalloproteinases-1 (TIMP-1)/matrix metalloproteinases-2 (MMP-2) signaling. Thirty-two rats were split into four categories: control, LPS (5 mg/kg, intraperitoneally [IP], single dose), LPS (5 mg/kg, IP, one dosage 30 min after last NBL treatment), + NBL (10 mg/kg oral gavage for three days), and NBL (10 mg/kg oral gavage for three days). Six hours after the administration of LPS, the lung tissues of the rats were removed for histopathological, biochemical, gene expression, and immunohistochemical analyses. Oxidative stress markers such as total oxidant status and oxidative stress index levels, leukocyte transendothelial migration markers such as MMP-2, TIMP-1, and ICAM-1 expressions in the case of inflammation, and caspase-3 as an apoptotic marker, significantly increased in the LPS group. NBL therapy reversed all these changes. The results of this study suggest that NBL has utility as a potential therapeutic agent to dampen inflammation in other lung and tissue injury modelshttps://www.mdpi.com/2077-0383/12/5/1721apoptosisinflammationlipopolysaccharidesnebivololoxidative stressrespiratory system
spellingShingle Esra Nurlu Temel
Mehtap Savran
Yalcın Erzurumlu
Nursel Hasseyid
Halil Ibrahim Buyukbayram
Gozde Okuyucu
Mehmet Abdulkadir Sevuk
Ozlem Ozmen
Ayse Coskun Beyan
The β1 Adrenergic Blocker Nebivolol Ameliorates Development of Endotoxic Acute Lung Injury
Journal of Clinical Medicine
apoptosis
inflammation
lipopolysaccharides
nebivolol
oxidative stress
respiratory system
title The β1 Adrenergic Blocker Nebivolol Ameliorates Development of Endotoxic Acute Lung Injury
title_full The β1 Adrenergic Blocker Nebivolol Ameliorates Development of Endotoxic Acute Lung Injury
title_fullStr The β1 Adrenergic Blocker Nebivolol Ameliorates Development of Endotoxic Acute Lung Injury
title_full_unstemmed The β1 Adrenergic Blocker Nebivolol Ameliorates Development of Endotoxic Acute Lung Injury
title_short The β1 Adrenergic Blocker Nebivolol Ameliorates Development of Endotoxic Acute Lung Injury
title_sort β1 adrenergic blocker nebivolol ameliorates development of endotoxic acute lung injury
topic apoptosis
inflammation
lipopolysaccharides
nebivolol
oxidative stress
respiratory system
url https://www.mdpi.com/2077-0383/12/5/1721
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