Protective Effects of Edaravone Against Hypoxia-Induced Lethality in Mice

Abstract

Edaravone has been recently used for the treatment of acute cerebral infarction. However, there is no data on the protective effects of this drug against hypoxia-induced lethality. Here, we aimed to evaluate the protective effects of edaravone against hypoxia-induced lethality and oxidative stress in mice through three experimental models of hypoxia. Materials and Methodsmale Swiss albino mice were randomly housed in groups of 10. Mice received single i.p. injections of edaravone for four consecutive days. Three experimental models of hypoxia: asphyctic, circulatory, and haemic were applied in this study. Oxidative stress, lipid peroxidation and glutathione content were assessed after hypoxia induction. ResultsSignificant protective activities were observed in all models of hypoxia. Antihypoxic activities were highly significant in asphytic and circulatory hypoxia. These effects were dose-dependent. Edaravone, at 5 mg kg-1, showed statistically significant activities concerning the control groups. Edaravone significantly prolonged the latency for death. At 2.5 mg kg-1, it prolonged survival time (26.08 {+/-} 0.79 min). This effect was statistically significant (P<0.05). Also, edaravone significantly inhibited hypoxia-induced oxidative stress (lipid peroxidation and glutathione oxidation) in three models of hypoxia. ConclusionsEdaravone showed an excellent protective effect against hypoxia in all tested models and decreased the oxidative stress in the brain tissue of hypoxic mice. Notably, results showed significant and dose-dependent effects on the models of asphytic and circulatory hypoxia. The antioxidant activity itself might be a proposed mechanism for the antihypoxic activities of this drug. Impact statementThis study provides a novel proof-of-concept for a FDA approved drug, which will open a new area of research in the field and drug repurposing.