Antidepressant-like effect of a new selenium-containing compound is accompanied by a reduction of neuroinflammation and oxidative stress in lipopolysaccharide-challenged mice

Abstract

Organoselenium compounds and indoles have gained attention due to their wide range of pharmacological properties. Depression is a recurrent and disabling psychiatric illness and current evidences support that oxidative stress and neuroinflammation are mechanisms underlying the pathophysiology of this psychiatric condition. Here, we evaluated the effect of 3-((4-chlorophenyl)selanyl)-1-methyl-1H-indole (CMI) in lipopolysaccharide (LPS)-induced depressive-like behaviour, neuroinflammation and oxidative stress in male mice. CMI pre-treatment (20 and 50 mg/kg, intragastrically) significantly attenuated LPS (0.83 mg/kg, intraperitoneally)-induced depressive-like behaviour in mice by reducing the immobility time in the tail suspension test (TST) and forced swimming test (FST). CMI pre-treatment ameliorated LPS-induced neuroinflammation by reducing the levels of interleukin (IL)-1β, IL-4 and IL-6 in the hippocampus and prefrontal cortex, as well as markers of oxidative damage. Additionally, we investigated the toxicological effects of CMI (200 mg/kg, i.g.) in the liver, kidney and brain through determination of the activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), δ-aminolevulinate dehydratase (δ-ALA-D) and creatinine levels. These biomarkers were not modified, indicating the possible absence of neuro-, hepato- and nephrotoxic effects. Our results suggest that CMI could be a therapeutic approach for the treatment of depression and other neuropsychiatric disorders associated with inflammation and oxidative stress.

Licofelone Attenuates LPS-induced Depressive-like Behavior in Mice: A Possible Role for Nitric Oxide

“…Based on the neuroinflammation hypothesis of depression, LPS-received mice are extensively used to evaluate the underlying mechanisms of depression (8,9). Licofelone ([2, 2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2, 3, dihydro-1H-pyrrolizine-5-yl]-acetic acid) is a substrate analogue of AA and consequently inhibits 5-LOX, COX-1 and COX-2, reducing production of eicosanoid (10).…”

Haloperidol Abrogates Matrix Metalloproteinase-9 Expression by Inhibition of NF-κB Activation in Stimulated Human Monocytic Cells

“…Many clinical and experimental studies have provided converging evidence of the central role of MMP-9 in the pathogenesis of inflammatory brain disorders [ 55 ]. The manipulation of LPS treatment could induce neuroinflammation and neurological symptoms similar to those of neurodegenerative diseases [ 56 ]. As expected that the marked enhancement of MMP-9 activity was noted in the brain region of intracerebral LPS-microinjected B6 mice when compared with saline-microinjected mice, these results were consistent with the findings of an earlier investigation [ 57 ].…”

Selenides and Diselenides: A Review of Their Anticancer and Chemopreventive Activity

“…Prevention of oxidative damage and radical scavenging potential were found for the indol-selenide derivative 51 [ 88 ] and the 6-arylselanylpurines 52a and 52b [ 89 ], respectively. Apart from preventing oxidative stress, compound 51 did not show hepatic, renal or cerebral toxicity.…”