Probucol Alleviates Lipopolysaccharide Induced Anxiety- and Depression-Like Behavior via Suppressing Neuroinflammation and Oxidative Stress

Anxiety manifests across numerous psychiatric conditions. Studies have shown the importance of inflammation and oxidative stress in anxiety disorders. Probucol is an antioxidant and lipid-lowering drug that is in clinical use. The objective of this research was to explore how probucol can protect against anxiety- and depression-like behaviors induced by lipopolysaccharide (LPS), and to elucidate the mechanisms involved. For this purpose, mice received 30 mg/kg of probucol (orally, 7 consecutive days) or vehicle (1% Dimethyl sulfoxide, DMSO) prior to administration of LPS (0.83 mg/kg, intraperitoneal). Anxiety-like behaviors were subsequently assessed using the open field test (OFT), elevated plus maze (EPM), and light dark test (LDT). Depression-like behaviors were evaluated through the tail suspension test (TST) and forced swimming test (FST). The activities of antioxidant enzymes and levels of malondialdehyde (MDA) were assayed. Histopathologic examination was performed and IBA-1 expression was detected immunohistochemically. In addition, the MTS assay was employed to assess cell viability and/or proliferation in BV-2 cells and a clonogenic survival assay was conducted. Tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), reactive oxygen species (ROS) and nitric oxide (NO) were determined using ELİSA. This study demonstrated that treatment with probucol reduced anxiety- and depression-like behaviours. It also revealed that probucol showed potential improvement by reducing inflammatory and oxidative damage as well as histopathological alterations. IBA-1 expression, which increased in response to neuroinflammation, decreased with the application of probucol. These results indicate that probucol has the potential to mitigate anxiety- and depression-like behavior in mice via suppressing inflammation and oxidative stress.