HydroMg attenuates doxorubicin-induced myocardial injury via promoting mitochondrial function

Abstract

JOURNAL/mgres/04.03/01612956-202701000-00005/figure1/v/2026-09-13T085902Z/r/image-tiff In contrast to molecular hydrogen's intrinsic limitations, HydroMg's structural optimization shortens gastrointestinal transit, reducing hydrogen dissipation while enhancing cellular bioavailability. However, it remains unclear whether it also provides protection against cardiac injury. Here, we investigated the cardioprotective effect of HydroMg, a sustained-release hydrogen donor, against doxorubicin-induced cardiac injury. In vitro studies showed that 1 μg/mL HydroMg treatment attenuated doxorubicin-induced cardiomyocyte death by inhibiting apoptosis, reducing reactive oxygen species production, and restoring mitochondrial membrane potential. The cardioprotective effect of HydroMg (20, 100, 500, and 1000 mg/kg) was further validated in doxorubicin-induced mice. The 100 mg/kg HydroMg group exhibited 35.7% lower mortality than doxorubicin-treated controls. Additionally, HydroMg treatment significantly improved cardiac function and increased left ventricular ejection fraction by 12.44% compared with the doxorubicin-only group. Mechanistically, HydroMg treatment alleviated mitochondrial dysfunction in the doxorubicin-induced cardiotoxicity mouse model by scavenging reactive oxygen species to dually suppress ferroptosis (via solute carrier family 7 member 11/glutathione peroxidase 4 axis upregulation) and apoptosis (characterized by caspase-3 downregulation and Bcl-2 upregulation). Overall, HydroMg treatment inhibits doxorubicin-induced mitochondrial dysfunction by attenuating reactive oxygen species overproduction, thereby suppressing ferroptosis and apoptosis.