Manganese dipyridoxyl diphosphate (MnDPDP) is a contrast agent for magnetic resonance imaging (MRI) of the liver. Aims of the study were to examine if MnDPDP possesses superoxide dismutase (SOD) mimetic activity in vitro, and if antioxidant protection can be demonstrated in an ex vivo rat heart model. Superoxide ((.)O(2)(-)) and hydroxyl radicals ((.)OH(-)) were generated in xanthine oxidase and Fenton reactions. Spin adducts with 5,5-dimethyl-1-pyrroline-N-oxide were detected by electron spin resonance spectroscopy. Contractile function and enzyme release were monitored in rat hearts during hypoxia-reoxygenation. Low mu M concentrations of MnDPDP and its metabolite Mn dipyridoxyl ethylene-diamine (MnPLED) dismutated (.)O(2)(-), but showed no activity in Fenton or catalase reactions. MnDPDP 30 mu M improved contractile function and reduced enzyme release in rat hearts during reoxygenation, It is concluded that MnDPDP and MnPLED possess SOD mimetic activities and may thereby protect the heart in oxidative stress. (C) 1999 Academic Press.