Protective Effect of Edaravone against Cationic Lipid-Mediated Oxidative Stress and Apoptosis

Liposomes containing ionizable cationic lipids have been widely used for the delivery of nucleic acids such as small-interfering RNA and mRNA. The utility with a permanent positive charge, however, is limited to in vitro transfection cultured cells due its dose-limiting toxic side effects observed animals. Several reports suggested that permanently charged induce reactive oxygen species (ROS) ROS-mediated toxicity cells. We therefore hypothesized concomitant use ROS inhibitor could reduce improve drug efficacy. In this study, suppression was evaluated using an scavenger, edaravone, which low-molecular-weight antioxidant clinically approved acute-phase cerebral infarction amyotrophic lateral sclerosis. Cell viability assay mouse macrophage-like cell line RAW264 indicated edaravone were not able suppress cytotoxicity induced by liposomes comprised monovalent lipid N-(1-[2,3-dioleyloxy]propyl)-N,N,N-trimethylammonium chloride (DOTMA) over short period time. Cationic lipids-induced necrosis assumed be involved upon short-term exposure liposomes. On other hand, significant improvement when treatment followed 24 h. It also confirmed apoptosis inhibition elimination might contributed effect. These results suggest continuous administration adverse reactions therapeutic