NecroX-5 prevents hypoxia/reoxygenation injury by inhibiting the mitochondrial calcium uniporter

Preservation of mitochondrial function is essential to limit myocardial damage in ischaemic heart disease. We examined the protective effects and mechanism of a new compound, NecroX-5, on rat heart mitochondria in a hypoxia/reoxygenation (HR) model. NecroX-5 reduced mitochondrial oxidative stress, prevented the collapse in mitochondrial membrane potential, improved mitochondrial oxygen consumption, and suppressed mitochondrial Ca-2 overload during reoxygenation in an in vitro rat heart HR model. Furthermore, NecroX-5 reduced the ouabain- or histamine-induced increase in mitochondrial Ca-2. These findings suggest that NecroX-5 may act as a mitochondrial Ca-2 uniporter inhibitor to protect cardiac mitochondria against HR damage.