P1623Activation of invariant natural killer T cells by alpha-galactosylceramide ameliorates doxorubicin-induced cardiotoxicity in mice

Abstract Objective Doxorubicin (DOX) is an effective antineoplastic agent commonly used to treat many types of cancer but its clinical use is limited because of cardiotoxicity, which might proceed to irreversible cardiac dysfunction in a dose-dependent manner. The precise mechanism of DOX-induced cardiotoxicity is still not fully elucidated but it has been reported that cardiac inflammation is involved in the cardiotoxicity. Invariant natural killer T (iNKT) cells, a unique subset of T lymphocytes that recognize glycolipid antigens and secrete a large amount of Th1 and Th2 cytokines on activation, have been shown to play crucial roles in the regulation of immune responses. However, it remains unclear whether iNKT cells are involved in DOX-induced cardiotoxicity. Methods and results Male C57BL/6J mice were administered DOX (20mg/kg body weight single intraperitoneal injection; n=28) or vehicle (Vehicle; n=6). DOX-administered mice were further divided into 2 groups; α-galactosylceramide (αGC, 0.1μg/g body weight twice intraperitoneal injection; DOX-αGC; n=14), which specifically activates iNKT cells, or phosphate-buffered saline alone (PBS; DOX-PBS; n=14) 4 days before and 3 days after DOX administration. Survival rate at 14 days after DOX/Vehicle administration was significantly lower in DOX-PBS than in Vehicle (71% vs. 100%, P