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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MDPI AG
2023-02-01
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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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series | Journal of Clinical Medicine |
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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