Knowledge Bank

Doxorubicin, a widely used chemotherapeutic agent, generates free radicals which may increase lipid peroxidation and oxidative stress. Research suggests that sucrose increases oxidative stress; conversely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) limit oxidative stress and lipid peroxidation in the brain of mice treated with doxorubicin. It is unknown how the combination of sucrose and omega-3 fatty acids impacts lipid peroxidation in metabolically important tissues such as the liver in the presence of chemotherapy or mammary tumors. Livers from mouse models of breast cancer (Tumor model: n=32; 8/diet) and chemotherapy (Chemo model: n=40;10/diet) were analyzed for 4-hydroxynonenal (4-HNE), a lipid peroxidation marker, using an enzyme-linked immunoabsorbent assay. In both experiments, 8-9 week old female C57BL/6 mice were ovariectomized and randomized to diets one week later. Tumor model mice were fed low sucrose diets, with either 0% or 2% kcal from EPA+DHA. Two weeks later, mice were injected with metastatic mammary tumor cells or control; after 21 days, tissues were collected. Chemo model mice were fed low sucrose, 0% or 2% kcal EPA+DHA diets, or high sucrose, 0% or 2% kcal EPA+DHA diets. Mice were injected with doxorubicin based chemotherapy or saline two and four weeks later; tissues were collected 11 days after second injection. Mean liver 4-HNE in tumor mice (0.0649ug HNE-BSA/ugProtein; SEM 0.0066) vs. control (0.0613ug HNEBSA/ugProtein; SEM 0.0066) was not significantly different (p=0.71) and did not differ by diet (p=0.54). Similarly, mean liver 4-HNE in chemo mice (0.0817ug HNE-BSA/ugProtein; SEM 0.0114) vs. control (0.0877ug HNE-BSA/ugProtein; SEM 0.0117) was not significantly different (p=0.72) and did not differ by diet (p=0.42). In conclusion, we found no differences in liver lipid peroxidation in chemotherapy-treated or tumor mice vs. controls when fed varying levels of sucrose and EPA+DHA.