Hong-Yu Jiang, Gui-Ru Wang, Ya-Qiong Hong, Hong-Mei Zhang and Miao-Miao Li
Health Examination Center & Department of Gerontology, The First Hospital of Jilin University, Changchun 130021, China
Doxorubicin (DOX) is one of the most effective chemotherapeutic drugs; however, cardiac toxicity compromises its clinical usefulness. Low doses radiation (LDR) induces an adaptive effect or hormesis, showing a protective effect on subsequent challenges-induced damage in vitro and in vivo. Our study was designed to investigate whether LDR pretreatment could against DOX-induced acute cardiotoxicity and its possible molecular mechanisms. LDR pretreatment significantly protected against DOX-induced myocardial damage which was characterized by conduction abnormalities, increased serum creatine kinase (CK), and lactate dehydrogenase (LDH) and pathological injury. As indicators of oxidative stress, DOX caused significant increasing levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and reduction in activities of antioxidant enzymes including glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD). LDR pretreatment significantly attenuated DOX-induced oxidative injury. Additionally, DOX induced significantly cell apoptotic was determined by the TUNEL method. DOX induced cell apoptosis via mitochondrial pathway, which was proved by mitochondrial membrane potential (ΔΨm) change, up-regulated Bax, caspase-9 and caspase-3 expressions and while down-regulated the expression of Bcl-2. LDR pretreatment significantly ameliorated these apoptotic actions of DOX. Collectively, these findings indicate that LDR possesses a protective effect against DOX-induced acute cardiotoxicity via suppressing oxidative stress and mitochondria-dependent apoptosis.
Keywords: Doxorubicin, cardiac toxicity, low doses radiation, oxidative stress, apoptosis.