Cardioprotective effects of Oroxylum indicum extract against chemotherapeutics‐induced cardiotoxicity

Abstract

Cancer chemotherapy, especially doxorubicin (DOX) and cyclophosphamide (CPS) is commonly associated with adverse effects such as myelosuppression and cardiotoxicity. At this time, little approved therapeutic options are available for the management of chemotherapy-associated cardiotoxicity. Thus, identification of novel therapeutics, with potent cardioprotective effects and minimal adverse effects are pertinent in chemotherapy-induced cardiotoxicity. Oroxylum indicum extract (OIE, Sabroxy®) is a natural product known to possess several biological functions including antioxidant, anti-inflammatory and cytoprotective effects. This study was designed to examine whether OIE extract confers protection against chemotherapy-induced cardiotoxicity, and explored potential mechanism involved. Adult male mice were treated with DOX and CPS, OIE or a combination of OIE and DOX & CPS. Swimming test was performed to assess cardiac function. Markers of oxidative stress were assessed by levels of reactive oxygen species (ROS), nitrite, hydrogen peroxide, catalase and glutathione content. Activity of interleukin converting enzyme and cyclooxygenase was determined as markers of inflammation. Mitochondrial function was assessed by measuring complex I activity. Apoptosis was assessed by caspase and protease activity. Mice treated with DOX and CPS exhibited reduced swim rate, increased oxidative stress markers, increased markers of inflammation and apoptosis. These effects were prevented by co-administration of OIE. Furthermore, computational molecular docking revealed potential binding of DOX and CPS to tyrosine hydroxylase and OIE as a potential protective agent. These data indicated that OIE counteracts chemotherapy-induced cardiotoxicity through inhibition of ROS-mediated apoptosis. Taken together, our findings suggested that OIE possesses potential as a means to counteract potentially fatal cardiac complications associated with chemotherapy treatment.