LQFM212, a piperazine derivative, exhibits potential antioxidant effect as well as ameliorates LPS-induced behavioral, inflammatory and oxidative changes

• Published in: Life sciences (1973) Vol. 312; p. 121199
• Main Authors: Moreira, Lorrane Kelle da Silva, Turones, Larissa Córdova, Campos, Hericles Mesquita, Nazareth, Aline Martins, Thomaz, Douglas Vieira, Gil, Eric de Souza, Ghedini, Paulo César, Rocha, Fábio Fagundes da, Menegatti, Ricardo, Fajemiroye, James Oluwagbamigbe, Costa, Elson Alves
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.01.2023
• Subjects: Animals; Antioxidants - metabolism; Antioxidants - pharmacology; Cytokines; Cytokines - metabolism; Depressive behavior; Lipopolysaccharides - pharmacology; Mice; Neuroinflammation; Neuroinflammatory Diseases; Oxidative Stress; Pleurisy; Oxidative stress; Neuroinflammation; Cytokines; Depressive behavior
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2022.121199

Oxidative stress, impaired antioxidant defense and neuroinflammation are often associated with the onset and progression of neuropsychiatric diseases. Conversely, several piperazine compounds presents beneficial neuropharmacological effects as well as antioxidant activity, and some derivatives combine both activities. LQFM212 (2,6-di-tert-butyl-4-((4-(2-hydroxyethyl)piperazin-1-yl)methyl)phenol) was synthesized to produce effects on CNS and to have an additional antioxidant effect. Previous preclinical tests have been shown anxiolytic- and antidepressant-like effects of LQFM212 in mice. Herein, the main objective was to verify the possible antioxidant potential and the effects of LQFM212 against behavioral changes, inflammatory and oxidative markers induced by lipopolysaccharide (LPS). Initially, antioxidant potential of LQFM212 was evaluated by electrochemical assays. Afterwards, the effects of oral treatment with LQFM212 were evaluated in mice using LPS-induced models of systemic or local inflammation. In LPS-induced neuroinflammation, LQFM212 treatment reverted changes caused by LPS, demonstrated by attenuated anxiogenic- and depressive-like behaviors, reduced pro-inflammatory cytokines (TNF-α and IL-1β) and increased anti-inflammatory cytokines (IL-4 and IL-10) on serum, and also improved oxidative stress-related changes (levels of nitrite, malondialdehyde, glutathione and carbonylated protein, and superoxide dismutase, catalase, myeloperoxidase and cholinesterase activities) on brain cortex and hippocampus. However, LQFM212 treatment did not attenuate the inflammatory changes in LPS-induced pleurisy model. LQFM212 presents antioxidant activity and ameliorates behavioral, inflammatory and oxidative changes after LPS-induced neuroinflammation model. These effects do not seem to be secondary to a peripheral anti-inflammatory action of LQFM212, since this compound failed to attenuate the inflammatory changes in LPS-induced pleurisy model.