Search

Abstract Introduction Doxorubicin is a chemotherapeutic drug used to treat various cancers. Exercise training (ET) can attenuate some cardiotoxic effects of doxorubicin (DOX) in tumor-free animals. However, the ET effects on cardiac function and glucose metabolism in DOX-treated breast cancer models remain unclear. Objectives This study investigated ET-induced structural, functional, vascular, oxidative stress, and plausible glucose uptake alterations of the left ventricle (LV) in a murine breast cancer model during DOX treatment. Methods Female FVB/N-mice were divided to tumor-free groups with or without voluntary wheel-running ET and those inoculated subcutaneously with mammary tumor-derived I3TC-cells with or without exercise or DOX treatment (5 mg/kg/week). Mice underwent 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography and echocardiography after two and four DOX-doses. The cardiac histology, oxidative stress, maximal metabolic enzyme activities, and mitochondrial respiration were analyzed. Results DOX increased LV glucose uptake (LVGU) and mitochondrial uncoupling and decreased running activity, LV-weight, and ejection fraction (EF). In DOX-treated group ET blunted the increase in LVGU, increased LV-weight and EF, and lowered LV lactate dehydrogenase activity. DOX-treated exercised mice did not differ from tumor-bearing group without DOX in LVGU or from the tumor-free ET-group in LV-weight or EF whereas unexercised DOX-treated group did. ET also increased LV citrate synthase activity in tumor-bearing animals. There was an inverse association between LVGU and EF and LV-weight. Conclusion In a murine breast cancer model, voluntary ET moderated DOX-induced cardiotoxicities such as increased LVGU, LV-atrophy and decreased EF. This suggests that ET might benefit patients with cancer undergoing doxorubicin treatment by mitigating cardiotoxicity.

Introduction: The possible beneficial effects of physical activity during doxorubicin treatment of breast cancer need further investigation as many of the existing studies have been done on non-tumor-bearing models. Therefore, in this study, we aim to assess whether short-term voluntary wheel-running exercise during doxorubicin treatment of breast cancer-bearing mice could induce beneficial cardiac effects and enhance chemotherapy efficacy.Methods: Murine breast cancer I3TC cells were inoculated subcutaneously to the flank of female FVB mice (n = 16) that were divided into exercised and non-exercised groups. Two weeks later, doxorubicin treatment was started via intraperitoneal administration (5 mg/kg weekly for 3 weeks). Organs were harvested a day after the last dose.Results: The tumor volume over time was significantly different between the groups, with the exercising group having lower tumor volumes. The exercised group had increased body weight gain, tumor apoptosis, capillaries per cardiomyocytes, and cardiac lactate dehydrogenase activity compared to the unexercised group, but tumor blood vessel density and maturation and tumor and cardiac HIF1-α and VEGF-A levels did not differ from those of the non-exercised group.Discussion: We conclude that even short-term light exercise such as voluntary wheel running exercise can decrease the subcutaneous mammary tumor growth, possibly via increased tumor apoptosis. The increase in cardiac capillaries per cardiomyocytes may also have positive effects on cancer treatment outcomes.

Climate-induced warming and increased river inflows are forcing the Baltic Sea to radical changes in the near future; organisms living in this brackish-water ecosystem are already experiencing osmotic stress, which, together with thermal stress, may have severe consequences on the ecosystem. The aim of this work was to study the combined effect of decreasing salinity and increasing temperature on reproductive success and oxidative stress in zooplankton by using a calanoid copepod Acartia sp. as a model organism. The field study was conducted during summer 2020 in the western Gulf of Finland, using three sampling sites with naturally differing salinity levels. Additionally, the copepods from these sites were experimentally exposed to ambient or 3°C elevated temperature for 72 h. The copepods derived from the deepest and the most saline sampling site suffered less oxidative damage and exhibited relatively high reproduction, while the temperature treatment itself had little effect. On the other hand, the field-based monitoring data showed otherwise; temperature increased lipid peroxidation, glutathione-s-transferase activity, or both in all three sampling sites. Meanwhile, egg production rate was negatively associated with temperature in the area with the lowest salinity. Moreover, egg production rate decreased from June to September along with increasing temperatures in the mid-salinity sampling site, while similar change occurred also in the highest-salinity site between August and September. The combined effect of salinity and sampling date on reproduction indicates the importance of even subtle salinity changes on copepods. Moreover, the data suggest that the unusually strong heatwave was responsible for increased oxidative stress during the sampling season and possibly forced a trade-off between antioxidant activity and reproductive effort.