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. 2025;28(3):323-331.
doi: 10.22038/ijbms.2024.80608.17444.

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

Halil Asci  1   2 , Suleyman Emre Akin  3 , Hasan Ekrem Camas  3 , Ahmet Bindal  4 , Okan Kurtbolat  1 , Serife Tasan  5 , Abdurrahman Gulal  6 , Rumeysa Taner  2 , Turgut Kurt  7 , Ozlem Ozmen  5
Affiliations

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

Halil Asci et al. Iran J Basic Med Sci. 2025.

Abstract

Objectives: 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.

Keywords: ER stress; Inflammation Lipopolysaccharide; Rat; Respiratory system; SSRI.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Possible effects of fluvoxamine (FLV) on the lipopolysaccharide (LPS)-induced acute lung injury (ALI) model in rats
Figure 2
Figure 2
Statistical analysis of oxidative stress parameters of this study
Figure 3
Figure 3
Histopathological appearance of lungs among the groups of rats
Figure 4
Figure 4
Immuno expressions of Cas-3 (upper row) and TNF-α (below row) in lung tissues of rats
Figure 5
Figure 5
Expression levels of Cas-9, Cas-12, and CHOP in lung tissues of rats
Figure 6
Figure 6
Probable mechanism of Fluvoxamine’s healing effect on lipopolysaccharide (LPS)-induced lung injury of rats
See this image and copyright information in PMC

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