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Open AccessArticle

The Effects of Doxorubicin-based Chemotherapy and Omega-3 Supplementation on Mouse Brain Lipids

1
Department of Human Sciences, Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA
2
Neuroscience, College of Medicine, Columbus, OH 43210, USA
3
Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV 26506, USA
4
College of Medicine, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
5
Foods for Health Discovery Theme, The Ohio State University, Columbus, OH 43210, USA
*
Author to whom correspondence should be addressed.
Metabolites 2019, 9(10), 208; https://doi.org/10.3390/metabo9100208
Received: 23 August 2019 / Revised: 24 September 2019 / Accepted: 26 September 2019 / Published: 29 September 2019
(This article belongs to the Special Issue Cancer Metabolomics 2019)
Chemotherapy-induced cognitive impairment affects ~30% of breast cancer survivors, but the effects on how chemotherapy impacts brain lipids, and how omega-3 polyunsaturated fatty acid supplementation may confer protection, is unknown. Ovariectomized mice were randomized to two rounds of injections of doxorubicin + cyclophosphamide or vehicle after consuming a diet supplemented with 2% or 0% EPA+DHA, and sacrificed 4, 7, and 14 days after the last injection (study 1, n = 120) or sacrificed 10 days after the last injection (study 2, n = 40). Study 1 whole brain samples were extracted and analyzed by UHPLC-MS/MS to quantify specialized pro-resolving mediators (SPMs). Lipidomics analyses were performed on hippocampal extracts from study 2 to determine changes in the brain lipidome. Study 1 results: only resolvin D1 was present in all samples, but no differences in concentration were observed (P > 0.05). Study 2 results: chemotherapy was positively correlated with omega-9 fatty acids, and EPA+DHA supplementation helped to maintain levels of plasmalogens. No statistically significant chemotherapy*diet effect was observed. Results demonstrate a limited role of SPMs in the brain post-chemotherapy, but a significant alteration of hippocampal lipids previously associated with other models of cognitive impairment (i.e., Alzheimer’s and Parkinson’s disease). View Full-Text
Keywords: specialized pro-resolving mediators; hippocampus; EPA; DHA; lipidomics; chromatography; mass spectrometry specialized pro-resolving mediators; hippocampus; EPA; DHA; lipidomics; chromatography; mass spectrometry
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Bennouna, D.; Solano, M.; Orchard, T.S.; DeVries, A.C.; Lustberg, M.; Kopec, R.E. The Effects of Doxorubicin-based Chemotherapy and Omega-3 Supplementation on Mouse Brain Lipids. Metabolites 2019, 9, 208.

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