Insights into mitochondrial creatine kinase: examining preventive role of creatine supplement in doxorubicin-induced cardiotoxicity

Doxorubicin (Dox) is an effective and commonly used anticancer drug; however, it leads to several side effects including cardiotoxicity which contributes to poor quality of life for cancer patients. Creatine (Cr) is a promising intervention to alleviate Dox-induced cardiotoxicity. This study aimed to examine the effects of Cr beforeDox on cardiac mitochondrial creatine kinase (MtCK). Male rats were randomly assigned to one of two 4-week Cr feeding interventions (standard Cr diet or Cr loading diet) or a control diet (Con, <i>n</i> = 20). Rats in the standard Cr diet (Cr1, <i>n</i> = 20) were fed 2% Cr for 4-weeks. Rats in the Cr loading diet (Cr2, <i>n</i> = 20) were fed 4% Cr for 1-week followed by 2% Cr for 3-weeks. After 4-weeks, rats received either a bolus injection of 15 mg/kg Dox or a placebo saline injection (Sal). Five days post-injections left ventricle (LV) was excised and analyzed for MtCK expression using Western blot and ELISA. A significant drug effect was observed for LV mass (<i>p</i> < 0.05), <i>post hoc</i> testing revealed LV mass of Con + Dox and Cr2 + Dox was significantly lower than Con + Sal (<i>p</i> < 0.05). A significant drug effect was observed for MtCK (<i>p</i> = 0.03) through Western blot. A significant drug effect (<i>p</i> = 0.03) and interaction (<i>p</i> = 0.02) was observed for MtCK using ELISA. <i>Post hoc</i> testing revealed that Cr2 + Dox had significantly higher MtCK than Cr1 + Sal and Cr2 + Sal. Data suggest that a reduction in LV mass and MtCK may contribute to Dox-induced cardiotoxicity, and Cr supplementation may play a potential role in mitigating cardiotoxicity by preserving mitochondrial CK.