salinomycin and Liver-Diseases

Salinomycin, a monocarboxylic ionophore in Streptomyces albus, has been studied as an anti-cancer agent. However, we wondered whether salinomycin has another effect such as an anti-oxidant and hepatic protectant, because some chemical drugs treating human diseases were sometimes related with their toxic effects. Therefore, this study was conducted to examine the effects of salinomycin against oxidative stress and mitochondrial impairment in vivo and in vitro as well as the cellular mechanisms of action. In hepatocyte, salinomycin inhibited arachidonic acid (AA) + iron-induced apoptosis, mitochondrial dysfunction and ROS production. As a molecular mechanism, salinomycin induced autophagy through AMP-activated protein kinase (AMPK) activation, as assessed by the accumulation of acidic vesicle organelles, p62 and LC3-II. Moreover, these protective effects were blocked by AMPK inhibition, which indicates the importance of AMPK in the process of salinomycin's effects. In mice, oral administration of salinomycin protected against carbon tetrachloride (CCl

Topics: AMP-Activated Protein Kinases; Animals; Apoptosis; Arachidonic Acid; Autophagy; Carbon Tetrachloride; Cell Line, Tumor; Hep G2 Cells; Hepatocytes; Humans; Liver; Liver Diseases; Male; Mice; Mice, Inbred C57BL; Mitochondria; Oxidative Stress; Phosphorylation; Pyrans; Reactive Oxygen Species