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Nutrients 2016, 8(4), 243; doi:10.3390/nu8040243

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
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 3 March 2016 / Revised: 12 April 2016 / Accepted: 20 April 2016 / Published: 23 April 2016
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Abstract

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
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

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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