Abstract
Mitochondrial dysfunction figures prominently in post‐ischemic cardiac myocyte injury. A novel cytoprotective compound, TRO40303, can reduce infarct size following ischemia‐reperfusion injury in mice and prevent contractile dysfunction in vitro. To better understand how TRO40303 potentially mediates such protection from oxidative damage seen in ischemia‐reperfusion injury, we induced oxidative stress in neonatal rat cardiac myocytes (n>/=5/group) using hydrogen peroxide (100µmol/L) and assessed changes in intracellular calcium levels (via Rhod‐2AM and Fluo‐4AM), reactive oxygen species (ROS, via DCF), mitochondrial membrane potential (via TMRM), and mitochondrial permeability transition (mPT, via Calcein‐AM). H2O2 induced cytosolic and mitochondrial calcium overload, ROS production, loss of mitochondrial membrane potential, and mPT. BAPTA (50µmol/L), an intracellular calcium chelator, completely blocked oxidant‐induced calcium overload. NaCN (3mmol/L) significantly reduced ROS production implicating mitochondrial respiration as a primary source for ROS‐induced ROS production. Such oxidative damage was significantly attenuated by cyclosporin A (1µmol/L) and TRO40303 (3µmol/L). We conclude that TRO40303 may confer protection by attenuating calcium overload and ROS production, and subsequently, loss of mitochondrial membrane potential and mPT. Supported by TROPHOS SA.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call