Potential Role of Selenium to Ameliorate Doxorubicin Induced Cardiotoxicity in Male Rats

Abstract: Selenium (SE) is well known for its immune boosting, antioxidant, and anti-tumor properties. Doxorubicin (DOXO), a commonly used chemotherapy drug, causes cardiac-damage by increasing the level of reactive oxygen species (ROS). Selenium (SE) is well known for its immune boosting, antioxidant, and anti-tumor properties. Doxorubicin (DOXO), a commonly used chemotherapy drug, causes cardiac-damage by increasing the level of reactive oxygen species (ROS). SE has been shown to improve heart development dysregulation, CMY structural damage, antioxidant enzyme (GSH, and SOD) activity, and caspase-۳ (CASP۳) levels in the cardiac tissue. Furthermore, SE could reduce the inflammation marker, ICAM-۱ activity, and cardiotoxicity marker levels in the serum, cTn-۱ serum levels. Finally, SE may protect against cardiotoxicity by inhibiting the oxidative induced by doxorubicin.Objectives: The aim of the study is to investigate if selenium has protective role against the cardiotoxicity induced by DOXO in laboratory rats.Method: A total of ۳۲ male rats were used, and they were randomly divided into ۴-groups (۸ rats * in each group). The rats in the control group started drinking distilled water for the experiment period. Rats in the doxorubicin group (the induced group) were given ۲.۵ MG/KG three times per wek, continue for ۲-weeks. The second group was treated with SE only had SE administered at a dose of ۱ mg/kg, continue for ۲-weeks. Results: Doxorubicin induced cardiotoxicity, as shown by a significant increase (~P < ۰.۰۰۱) in the levels of cTnI, ICAM-۱, and caspase-۳. At the same time, the levels of GSH and SOD when compared to the control group, were significantly reduced (P < ۰.۰۰۱) in the cardiac tissues of rats in the doxorubicin treated group.  Histological changes and lesions were also caused by the Doxo. The administration of selenium was found to reduce cardiotoxicity, this can be proved by significant-decreases (p* < ۰.۰۰۱) in cardiac-TnI, ICAM-۱, casp-۳ and significant-increases (~P < ۰.۰۰۱) in SOD and GSH when compared to the DOXO group; and significant improvements (~P < ۰.۰۰۱) in the score for cardiomyopathy histopathological lesions.Conclusion: At the drugs-doses used in this study, selenium protected the hearts of rats from DOXO-induced cardiotoxicity. This is may related to the interfered and may ameloirate oxidative stress, inflammation, and the apoptotic pathway.

Keywords:

Cardiotoxicity Inflammatory , markers Oxidative , stress Apoptosis Selenium Doxorubicin