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

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.