Poster Topical Area: Dietary Bioactive Components
Location: Hall D
Poster Board Number: 346
Objective: Doxorubicin-based chemotherapy results in long-term cognitive deficits in about 30% of cancer survivors who receive the treatment. Increased neuroinflammation may be a contributing mechanism. Increasing omega-3 fatty acids (n-3 FAs) intake is a promising strategy to reduce inflammation in the brain. Thus, we hypothesized that a diet mixture of n-3 FAs (e.g., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) and low sucrose would significantly increase the concentration of n-3 FAs and decrease chemotherapy-induced inflammatory cytokines in the brain.
Method: Adult, female, ovariectomized BalbC mice were randomly assigned to 1 of 2 diets: either low sucrose diet with 2% kcal EPA + DHA (Low Suc, 2% EPA+DHA) or high sucrose without EPA + DHA (High Suc, no EPA + DHA). The mice received two saline or chemotherapy injections (75% human equivalent dose of doxorubicin and cyclophosphamide), administered one week and three weeks after starting diets. Mice were sacrificed 6 hours after the second injection; brains were collected and frozen at -80˚ C. One brain hemisphere was analyzed for gene expression of inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6)] using quantitative PCR (qPCR). The other hemisphere was analyzed for fatty acids using gas chromatography. Significant differences (p < 0.05) were determined using 2-way ANOVA.
Results: Brain EPA and DHA levels were significantly greater (p < 0.05 for both) in mice fed Low Suc, 2% EPA +DHA diet compared to High Suc, no EPA + DHA. There was a significant diet effect on IL-1β in cortex such that IL-1 β was lower in the Low Suc, 2% EPA+DHA group (p = 0.0013). There was a significant injection effect on hippocampal cytokines: in the chemotherapy group, IL-1β was lower (p = 0.0057) and IL-6 was higher (p = 0.252). No significant differences were seen in expression of TNF-α.
Conclusion: Our findings suggest that when brain EPA and DHA are increased, marker of inflammation IL-1β can be decreased after only 3 weeks of feeding a diet high in n-3 FAs and low in sucrose during doxorubicin-based chemotherapy treatment. Further studies of the anti-inflammatory and neuroprotective potential of administering n-3 FAs during chemotherapy is warranted.
Panchita Phuwamongkolwiwat - Chu
Post doctoral reseracher
The Ohio State University