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

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.

• Authors: Yan-Qin Wu, Rui-Li Dang, Mi-Mi Tang, Hua-Lin Cai, Huan-De Li, De-Hua Liao, Xin He, Ling-Juan Cao, Ying Xue, Pei Jiang
• Journal: Nutrients (Nutrients) Vol. 8 Issue 4 Pg. 243 (Apr 23 2016) ISSN: 2072-6643 [Electronic] Switzerland
• PMID: 27120616 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Fatty Acids, Omega-3
• Doxorubicin

Topics

• Animals
• Apoptosis (drug effects)
• Behavior, Animal (drug effects)
• Biomarkers
• Brain (drug effects)
• Central Nervous System Diseases (chemically induced, drug therapy)
• Depression (chemically induced, drug therapy)
• Dietary Supplements
• Doxorubicin (toxicity)
• Fatty Acids, Omega-3 (administration & dosage, therapeutic use)
• Gene Expression Regulation (drug effects)
• Inflammation (chemically induced, drug therapy)
• Male
• Oxidative Stress
• Rats
• Rats, Sprague-Dawley
• Swimming
• Weight Gain