Investigating the protective effects of fluvoxamine against sepsis-related acute lung injury through antiapoptotic, anti-inflammatory, and anti-oxidant features in rats

Objective(s): Acute lung injury (ALI) is characterized by severe hypoxia and alveolar damage, often caused by oxidative stress, endoplasmic reticulum stress (ERS), and apoptosis. Fluvoxamine (FLV), an antidepressant, has tissue-protective properties through various intracellular mechanisms. This stu...

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Main Authors: Halil Asci, Suleyman Emre Akin, Hasan Ekrem Camas, Ahmet Bindal, Okan Kurtbolat, Şerife Tasan, Abdurrahman Gulal, Rumeysa Taner, Turgut Kurt, Ozlem Ozmen
Format: Article
Language:English
Published: Mashhad University of Medical Sciences 2025-03-01
Series:Iranian Journal of Basic Medical Sciences
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Online Access:https://ijbms.mums.ac.ir/article_25368_f8d5d1d20907e7f3a91fe1f4c610e020.pdf
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author Halil Asci
Suleyman Emre Akin
Hasan Ekrem Camas
Ahmet Bindal
Okan Kurtbolat
Şerife Tasan
Abdurrahman Gulal
Rumeysa Taner
Turgut Kurt
Ozlem Ozmen
author_facet Halil Asci
Suleyman Emre Akin
Hasan Ekrem Camas
Ahmet Bindal
Okan Kurtbolat
Şerife Tasan
Abdurrahman Gulal
Rumeysa Taner
Turgut Kurt
Ozlem Ozmen
author_sort Halil Asci
collection DOAJ
description Objective(s): Acute lung injury (ALI) is characterized by severe hypoxia and alveolar damage, often caused by oxidative stress, endoplasmic reticulum stress (ERS), and apoptosis. Fluvoxamine (FLV), an antidepressant, has tissue-protective properties through various intracellular mechanisms. This study investigates the anti-inflammatory effects of  FLV used as an antidepressant in a lipopolysaccharide (LPS)-induced ALI model.Materials and Methods: Thirty-two female Wistar Albino rats aged 14–16 weeks and weighing 300–350 g, with 8 animals in each group, were divided into four groups: control, LPS, LPS+FLV, and FLV. After LPS administration, rats were euthanized, and histopathological analysis, immunohistochemistry for tumor necrosis factor-α (TNF-α) and caspase-3 (Cas-3), ELISA for oxidative stress markers, and PCR for CHOP, Cas-12, and Cas-9 gene expressions were conducted.Results: In the LPS group, lung tissue damage, increased inflammatory cell infiltration, increased Cas-3 and TNF-α expressions, increased oxidative stress markers, and increased CHOP, Cas-9, and Cas-12 mRNA expressions were observed compared to the control group. FLV treatment in the LPS+FLV group significantly reversed these effects in the LPS group.Conclusion: FLV exhibits protective effects against ALI by mitigating inflammation, ERS, and apoptosis via the CHOP/Cas-9/Cas-12 pathway. Further studies are needed to explore additional pathways and potential clinical applications of FLV.
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spelling doaj-art-7e748d971bb548c88fbf359d2551f78e2025-08-20T03:35:48ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742025-03-0128332333110.22038/ijbms.2024.80608.1744425368Investigating the protective effects of fluvoxamine against sepsis-related acute lung injury through antiapoptotic, anti-inflammatory, and anti-oxidant features in ratsHalil Asci0Suleyman Emre Akin1Hasan Ekrem Camas2Ahmet Bindal3Okan Kurtbolat4Şerife Tasan5Abdurrahman Gulal6Rumeysa Taner7Turgut Kurt8Ozlem Ozmen9Department of Pharmacology, Faculty of Medicine, Suleyman Demirel University, Isparta, TurkeyDepartment of Thoracic Surgery, Faculty of Medicine, Suleyman Demirel University, Isparta, TurkeyDepartment of Thoracic Surgery, Faculty of Medicine, Suleyman Demirel University, Isparta, TurkeyDepartment of Anesthesiology and Reanimation, Suleyman Demirel University, Isparta, TurkeyDepartment of Pharmacology, Faculty of Medicine, Suleyman Demirel University, Isparta, TurkeyDepartment of Pathology, Faculty of Veterinary Medicine, Burdur Mehmet Akif Ersoy University, Burdur, TurkeyVeterinarian, Isparta, TurkeyDepartment of Bioengineering, Institute of Science and Technology, Suleyman Demirel University Isparta, TurkeyVeterinary Technician, Faculty of Medicine, Suleyman Demirel University Isparta, TurkeyDepartment of Pathology, Faculty of Veterinary Medicine, Burdur Mehmet Akif Ersoy University, Burdur, TurkeyObjective(s): Acute lung injury (ALI) is characterized by severe hypoxia and alveolar damage, often caused by oxidative stress, endoplasmic reticulum stress (ERS), and apoptosis. Fluvoxamine (FLV), an antidepressant, has tissue-protective properties through various intracellular mechanisms. This study investigates the anti-inflammatory effects of  FLV used as an antidepressant in a lipopolysaccharide (LPS)-induced ALI model.Materials and Methods: Thirty-two female Wistar Albino rats aged 14–16 weeks and weighing 300–350 g, with 8 animals in each group, were divided into four groups: control, LPS, LPS+FLV, and FLV. After LPS administration, rats were euthanized, and histopathological analysis, immunohistochemistry for tumor necrosis factor-α (TNF-α) and caspase-3 (Cas-3), ELISA for oxidative stress markers, and PCR for CHOP, Cas-12, and Cas-9 gene expressions were conducted.Results: In the LPS group, lung tissue damage, increased inflammatory cell infiltration, increased Cas-3 and TNF-α expressions, increased oxidative stress markers, and increased CHOP, Cas-9, and Cas-12 mRNA expressions were observed compared to the control group. FLV treatment in the LPS+FLV group significantly reversed these effects in the LPS group.Conclusion: FLV exhibits protective effects against ALI by mitigating inflammation, ERS, and apoptosis via the CHOP/Cas-9/Cas-12 pathway. Further studies are needed to explore additional pathways and potential clinical applications of FLV.https://ijbms.mums.ac.ir/article_25368_f8d5d1d20907e7f3a91fe1f4c610e020.pdfer stressinflammationlipopolysaccharideratrespiratory systemssri
spellingShingle Halil Asci
Suleyman Emre Akin
Hasan Ekrem Camas
Ahmet Bindal
Okan Kurtbolat
Şerife Tasan
Abdurrahman Gulal
Rumeysa Taner
Turgut Kurt
Ozlem Ozmen
Investigating the protective effects of fluvoxamine against sepsis-related acute lung injury through antiapoptotic, anti-inflammatory, and anti-oxidant features in rats
Iranian Journal of Basic Medical Sciences
er stress
inflammation
lipopolysaccharide
rat
respiratory system
ssri
title Investigating the protective effects of fluvoxamine against sepsis-related acute lung injury through antiapoptotic, anti-inflammatory, and anti-oxidant features in rats
title_full Investigating the protective effects of fluvoxamine against sepsis-related acute lung injury through antiapoptotic, anti-inflammatory, and anti-oxidant features in rats
title_fullStr Investigating the protective effects of fluvoxamine against sepsis-related acute lung injury through antiapoptotic, anti-inflammatory, and anti-oxidant features in rats
title_full_unstemmed Investigating the protective effects of fluvoxamine against sepsis-related acute lung injury through antiapoptotic, anti-inflammatory, and anti-oxidant features in rats
title_short Investigating the protective effects of fluvoxamine against sepsis-related acute lung injury through antiapoptotic, anti-inflammatory, and anti-oxidant features in rats
title_sort investigating the protective effects of fluvoxamine against sepsis related acute lung injury through antiapoptotic anti inflammatory and anti oxidant features in rats
topic er stress
inflammation
lipopolysaccharide
rat
respiratory system
ssri
url https://ijbms.mums.ac.ir/article_25368_f8d5d1d20907e7f3a91fe1f4c610e020.pdf
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