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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Summary: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.
ISSN:2008-3866
2008-3874