# 1‑(Phenylselanyl)-2‑(p‑tolyl)indolizine Mitigates Lipopolysaccharide (LPS)-Induced Depressive-Like Behavior by Modulating Oxidative Stress and Inflammatory Markers

## TL;DR

A compound called MeSeI reduces depressive-like behavior in mice by reducing inflammation and oxidative stress caused by LPS.

## Contribution

MeSeI is shown to mitigate LPS-induced depression-like behavior through modulation of oxidative stress and inflammatory markers.

## Key findings

- MeSeI reduced reactive species and nitrite levels in astrocytes exposed to LPS.
- MeSeI prevented LPS-induced increases in IL-6 and NF-κB expression in the prefrontal cortex.
- MeSeI lowered plasma corticosterone levels and lipid peroxidation in mice.

## Abstract

1-(phenylselanyl)-2-(p-tolyl)­indolizine
(MeSeI)
is a selenoindolizine that showed antidepressant-like properties in
mice via monoaminergic and glutamatergic systems. This study aimed
to investigate the MeSeI effect on lipopolysaccharide (LPS)-induced
depressive-like behavior in mice as well as its effect on oxidative
stress parameters in primary astrocyte cultures challenged with LPS.
Primary astrocyte cultures were exposed to LPS (1 μg/mL) for
3 h and treated with MeSeI (5, 10, 15, 25 μM) for 48 h. MeSeI
reversed the LPS-induced increase in reactive species (RS) and nitrite
levels, restored the activity of antioxidant enzymes, and increased
the sulfhydryl content in astrocytes. Male Swiss mice
received MeSeI (10 mg/kg, intragastrically) 30 min prior to LPS administration
(0.83 mg/kg, intraperitoneally). After 24 h, the animals were subjected
to behavioral tests and then euthanized to remove the prefrontal cortex
(PFC) and plasma. MeSeI prevented LPS-induced depression-like behavior,
the increase in NF-κB and IL-6 expression, and IL-6 protein
levels, as well as RS levels and lipid peroxidation in the PFC, and
reduced plasma corticosterone levels induced by LPS. These findings
suggest that MeSeI exerts neuroprotective effects by modulating the
neuroinflammatory pathway and normalizing oxidative stress parameters,
indicating its potential as a therapeutic candidate for depression
treatment.