Background:
Anthracyclines such as
doxorubicin remain a primary treatment for
hematological malignancies and breast
cancers. However,
cardiotoxicity induced by
anthracyclines, possibly leading to
heart failure, severely limits their application. The pathological mechanisms of
anthracycline-induced cardiac injury are believed to involve
iron-overload-mediated formation of
reactive oxygen species (ROS),
mitochondrial dysfunction, and
inflammation. The dietary
thione,
ergothioneine (ET), is avidly absorbed and accumulated in tissues, including the heart. Amongst other cytoprotective properties, ET was shown to scavenge ROS, decrease proinflammatory mediators, and chelate
metal cations, including Fe2+, preventing them from partaking in redox activities, and may protect against mitochondrial damage and dysfunction. Plasma ET levels are also strongly correlated to a decreased risk of cardiovascular events in humans, suggesting a cardioprotective role. This evidence highlights ET's potential to counteract
anthracycline cardiotoxicity. Methods and Findings: We investigated whether ET supplementation can protect against cardiac dysfunction in mice models of
doxorubicin-induced
cardiotoxicity and revealed that it had significant protective effects. Moreover, ET administration in a mouse
breast cancer model did not exacerbate the growth of the
tumor or interfere with the chemotherapeutic efficacy of
doxorubicin. Conclusion: These results suggest that ET could be a viable co-
therapy to alleviate the cardiotoxic effects of
anthracyclines in the treatment of
cancers.