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

1
Institute of Clinical Pharmacy & Pharmacology, Second Xiangya Hospital, Central South University, Changsha 410011, China
2
Department of Pharmacy, Jining First People’s Hospital, Jining Medical University, Jining 272000, China
3
Department of Pharmacy, Hunan Cancer Hospital, Central South University, Changsha 410011, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Nutrients 2016, 8(4), 243; https://doi.org/10.3390/nu8040243
Received: 3 March 2016 / Revised: 12 April 2016 / Accepted: 20 April 2016 / Published: 23 April 2016
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 (ω-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 ω-3 PUFAs against DOX-induced behavioral changes and neurotoxicity. ω-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 ω-3 PUFAs supplementation significantly mitigated the behavioral changes induced by DOX. ω-3 PUFAs pretreatment also alleviated the DOX-induced neural apoptosis. Meanwhile, ω-3 PUFAs treatment ameliorated DOX-induced oxidative stress in the prefrontal cortex and hippocampus. Additionally, gene expression of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, and the protein levels of NF-κB and iNOS were significantly increased in brain tissues of DOX-treated group, whereas ω-3 PUFAs supplementation significantly attenuated DOX-induced neuroinflammation. In conclusion, ω-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. View Full-Text
Keywords: depression; neurotoxicity; ω-3 PUFAs; doxorubicin; oxidative stress; neuroinflammation depression; neurotoxicity; ω-3 PUFAs; doxorubicin; oxidative stress; neuroinflammation
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Wu, Y.-Q.; Dang, R.-L.; Tang, M.-M.; Cai, H.-L.; Li, H.-D.; Liao, D.-H.; He, X.; Cao, L.-J.; Xue, Y.; Jiang, P. Long Chain Omega-3 Polyunsaturated Fatty Acid Supplementation Alleviates Doxorubicin-Induced Depressive-Like Behaviors and Neurotoxicity in Rats: Involvement of Oxidative Stress and Neuroinflammation. Nutrients 2016, 8, 243.

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