NecroX as a Novel Class of Mitochondrial Reactive Oxygen Species and ONOO- Scavenger

Mitochondrial reactive oxygen species and reactive nitrogen species are proven to be major sources of oxidative stress in the cell, they play a prominent role in a wide range of human disorders resulting from nonapoptotic cell death The aim of this study is to examine the cytoprotective effect of the NecroX series against harmful stresses, including pro oxidant (tertiary butylhydroperoxide), doxorubicin, CCl4, and hypoxic injury In this study, these novel chemical molecules inhibited caspase independent cell death with necrotic morphology, which is distinctly different from apoptosis, autophagy, and necroptosis In addition, they displayed strong mitochondrial reactive oxygen species and ONOO- scavenging activity Further, oral administration of these molecules in C57BL/6 mice attenuated streptozotocin induced pancreatic islet beta cell destruction as well as CCl4 induced hepatotoxicity in vivo Taken together, these results demonstrate that the NecroX series are involved in the blockade of nonapoptotic cell death against mitochondrial oxidative stresses Thus, these chemical molecules are potential therapeutic agents in mitochondria related human diseases involving necrotic tissue injury