Apigenin, Selenium, and Combinations Are Effective in Preventing 5‐Fluorouracil Induced Cardiovascular Damage

Although chemotherapy is still a widely used primary treatment modality for many cancers, it is an accepted fact that it causes many undesirable side effects and toxicity. Until a new, side-effect-free treatment modality is developed, new resources will continue to be sought to prevent and reduce the adverse effects of chemotherapy. In this study, we investigated the potential of apigenin, selenium, and their combination to prevent cardiovascular toxicity induced by 5-fluorouracil (5FU), an important chemotherapeutic agent. The study consisted of control (C), 5FU, apigenin + 5FU (Api + 5FU), selenium + 5FU (Se + 5FU), and apigenin + selenium + 5FU (Api + Se + 5FU) groups. Api (50 mg/kg) and Se (0.5 mg/kg) were administered orally to rats for 7 days. On Day 5, 5FU was administered i.p. at a dose of 150 mg/kg. Administration of 5FU significantly reduced GSH levels and CAT and TrxR activities in both cardiac and thoracic aortic tissues. It also decreased Bcl-2 expression and increased Bax and Caspase-3 expression in cardiac tissue, while reducing Bcl-2 and increasing Bax expression in the thoracic aorta. Thoracic aortic MDA levels were also significantly elevated. On the contrary, oxidative stress and apoptosis were significantly decreased, and cardiovascular damage was attenuated in apigenin and selenium treated groups. In this study, it was determined that 5FU caused a higher level of toxicity to the heart compared to the thoracic aorta. In addition, both apigenin and selenium were shown to have significant protective effects on the cardiovascular system against 5FU toxicity. However, the cardiovascular protection against 5FU toxicity was found to be higher when apigenin and selenium were used together.