Long Chain Omega-3 Polyunsaturated Fatty Acid Supplementation Alleviates Doxorubicin-Induced Depressive-Like Behaviors and Neurotoxicity in Rats: Involvement of Oxidative Stress and Neuroinflammation

卷:8

Wu, Yan-Qin ; Dang, Rui-Li ; Tang, Mi-Mi ; Cai, Hua-Lin ; Li, Huan-De ; Liao, De-Hua ; He, Xin ; Cao, Ling-Juan ; Xue, Ying ; Jiang, Pei

Cent S Univ

关键词: depression;    neurotoxicity;    omega-3 PUFAs;    doxorubicin;    oxidative stress;    neuroinflammation;   

DOI  :  10.3390/nu8040243

学科分类：食品科学和技术

【 摘 要 】

Doxorubicin (DOX) is a chemotherapeutic agent widely used in human malignancies. Its long-term use can cause neurobiological side-effects associated with depression. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs), the essential fatty acids found in fish oil, possess neuroprotecitve and antidepressant activities. Thus, the aim of this study was to explore the potential protective effects of omega-3 PUFAs against DOX-induced behavioral changes and neurotoxicity. omega-3 PUFAs were given daily by gavage (1.5 g/kg) over three weeks starting seven days before DOX administration (2.5 mg/kg). Open-field test (OFT) and forced swimming test (FST) were conducted to assess exploratory activity and despair behavior, respectively. Our data showed that omega-3 PUFAs supplementation significantly mitigated the behavioral changes induced by DOX. omega-3 PUFAs pretreatment also alleviated the DOX-induced neural apoptosis. Meanwhile, omega-3 PUFAs treatment ameliorated DOX-induced oxidative stress in the prefrontal cortex and hippocampus. Additionally, gene expression of pro-inflammatory cytokines, including IL-1 beta, IL-6, and TNF-alpha, and the protein levels of NF-kappa B and iNOS were significantly increased in brain tissues of DOX-treated group, whereas omega-3 PUFAs supplementation significantly attenuated DOX-induced neuroinflammation. In conclusion, omega-3 PUFAs can effectively protect against DOX-induced depressive-like behaviors, and the mechanisms underlying the neuroprotective effect are potentially associated with its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.