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

Asci, Halil; Akin, Suleyman Emre; Camas, Hasan Ekrem; Bindal, Ahmet; Kurtbolat, Okan; Tasan, Serife; Gulal, Abdurrahman; Taner, Rumeysa; Kurt, Turgut; Ozmen, Ozlem

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-a (TNF-a) 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-a 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.

RESPIRATORY organs; LABORATORY rats; OXIDATIVE stress; ENDOPLASMIC reticulum; GENE expression

Iranian Journal of Basic Medical Sciences, 2025, Vol 28, Issue 3, p323

2008-3866

Academic Journal

10.22038/ijbms.2024.80608.17444