Long Chain Omega-3 Polyunsaturated Fatty Acid Supplementation Alleviates Doxorubicin-Induced Depressive-Like Behaviors and Neurotoxicity in Rats: Involvement of Oxidative Stress and Neuroinflammation.
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.
Institute of Clinical Pharmacy &amp; Pharmacology, Second Xiangya Hospital, Central South University, Changsha 410011, China. wuyanqin1992@163.com.
Yan-Qin
YQ
Wu
Department of Pharmacy, Jining First People's Hospital, Jining Medical University, Jining 272000, China. ruilidang@gmail.com.
Rui-Li
RL
Dang
Institute of Clinical Pharmacy &amp; Pharmacology, Second Xiangya Hospital, Central South University, Changsha 410011, China. tangmimi1989@163.com.
Mi-Mi
MM
Tang
Institute of Clinical Pharmacy &amp; Pharmacology, Second Xiangya Hospital, Central South University, Changsha 410011, China. ghostspecialist@163.com.
Hua-Lin
HL
Cai
Institute of Clinical Pharmacy &amp; Pharmacology, Second Xiangya Hospital, Central South University, Changsha 410011, China. lihuande1953@126.com.
Huan-De
HD
Li
Department of Pharmacy, Hunan Cancer Hospital, Central South University, Changsha 410011, China. liaodehua1125@126.com.
De-Hua
DH
Liao
Institute of Clinical Pharmacy &amp; Pharmacology, Second Xiangya Hospital, Central South University, Changsha 410011, China. hexin526@126.com.
Xin
X
He
Institute of Clinical Pharmacy &amp; Pharmacology, Second Xiangya Hospital, Central South University, Changsha 410011, China. caolingjuan@126.com.
Ling-Juan
LJ
Cao
Institute of Clinical Pharmacy &amp; Pharmacology, Second Xiangya Hospital, Central South University, Changsha 410011, China. xueying091@126.com.
Ying
Y
Xue
Department of Pharmacy, Jining First People's Hospital, Jining Medical University, Jining 272000, China. jiangpeicsu@sina.com.
Pei
P
Jiang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers; D001921:Brain / Q000187:drug effects; D002493:Central Nervous System Diseases / Q000139:chemically induced* / Q000188:drug therapy; D003863:Depression / Q000139:chemically induced* / Q000188:drug therapy; D019587:Dietary Supplements; D004317:Doxorubicin / Q000633:toxicity*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming; D015430:Weight Gain
D015415:Biomarkers; D015525:Fatty Acids, Omega-3; D004317:Doxorubicin
depression; doxorubicin; neuroinflammation; neurotoxicity; oxidative stress; ω-3 PUFAs