N-(3-((3-(trifluoromethyl)phenyl)selanyl)prop-2-yn-1-yl) benzamide ameliorates lipopolysaccharide-induced depression-like behavior in mice targeting inflammatory, apoptotic, and oxidative pathways.

The organoselenium compound CF3SePB has previously shown promise as an antidepressant due to its modulation of the serotonergic system. This study aimed to investigate the potential of CF3SePB to ameliorate depressive-like behaviors induced by lipopolysaccharide (LPS) in mice. Male Swiss mice were pretreated with CF3SePB (10 mg/kg, i. g.), vehicle (10 mL/kg, i. g.), or fluoxetine (20 mg/kg, i. p.), and 30 min later, they were treated with LPS (0.83 mg/kg, i. p.) or vehicle (10 mL/kg, i. p.). Twenty-four hours after LPS treatment, the forced swim test, tail suspension test, and splash test were conducted to assess depressive-like behaviors and open-field test was conducted to evaluate the locomotor activity. Mice were euthanized, and the hippocampal tissue was removed for biochemical parameters and gene expression analysis. Blood was also collected for corticosterone analysis. CF3SePB effectively reversed LPS-induced depressive-like behaviors without affecting locomotion. Furthermore, CF3SePB prevented the increase in the expression of the pro-inflammatory genes nuclear factor kappa B (NF-κB), NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome, and cyclooxygenase-2 (COX-2) and the apoptotic genes caspase-1, caspase-8, and BCL-2-Associated X Protein (BAX) induced by LPS in hippocampus, indicating its potential to target inflammation and neuronal death pathways. Furthermore, CF3SePB increased BCL-2 and BDNF, targets associated with neuronal survival. It also reduced reactive species (RS) and lipid peroxidation levels in hippocampus induced by LPS. Additionally, the treatment with the compound reduced the LPS-induced plasma corticosterone levels. These findings highlight the potential of CF3SePB as a novel therapeutic agent for depression, particularly in models involving inflammation-mediated mechanisms.