Agomelatine prevented depression in the chronic restraint stress model through enhanced catalase activity and halted oxidative stress

• Published in: PloS one 2024-02, Vol.19 (2), p.e0289248-e0289248
• Main Authors: Xu, Jiaxi, Zhu, Cheng, Jin, Piaopiao, Sun, Wangdi, Yu, Enyan
• Format: Article
• Language: English
• Subjects: Antidepressants; B cells; Brain; Complications and side effects; Depression, Mental; Diagnosis; Enzyme-linked immunosorbent assay; Oxidative stress; Patient outcomes; Prevention; Superoxide
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0289248

Agomelatine (AGO) is an antidepressant with unique pharmacological effects; however, its underlying mechanisms remain unknown. In this study, we examined agomelatine's effects on catalase activity, oxidative stress, and inflammation. Chronic restraint stress (CRS) model mice were established over 4 weeks, and AGO 50 mg/kg was administered to different groups alongside a deferasirox (DFX) 10 mg/kg gavage treatment. Behavioral tests were performed to assess the effect of AGO on the remission of depression-like behaviors. Meanwhile, the expression of CAT, the oxidative stress signaling pathway and inflammatory protein markers were assessed using ELISA, qRT-PCR, Western blot, and immunohistochemistry. Four weeks of AGO treatment significantly improved depression-like behavior in mice through the activation of catalase in the hippocampus and serum of the model mice, increased superoxide dismutase expression, reduced malondialdehyde expression, and reduced oxidative stress damage. Deferasirox was found to offset this therapeutic effect partially. In addition, the inflammatory pathway (including nuclear factor-κB and nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha) was not significantly altered. AGO can exert antidepressant effects by altering oxidative stress by modulating catalase activity.