BGP-15 Protects against Oxidative Stress- or Lipopolysaccharide-Induced Mitochondrial Destabilization and Reduces Mitochondrial Production of Reactive Oxygen Species

• Published in: PloS one Vol. 12; no. 1; p. e0169372
• Main Authors: Sumegi, Katalin, Fekete, Katalin, Antus, Csenge, Debreceni, Balazs, Hocsak, Eniko, Gallyas, Jr, Ferenc, Sumegi, Balazs, Szabo, Aliz
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.01.2017; Public Library of Science (PLoS)
• Subjects: Analysis; Animal diseases; Animals; Antioxidants; Apoptosis; Bacteria; Benzimidazoles - metabolism; Biology and Life Sciences; Carbocyanines - metabolism; Cell culture; Cell death; Cell Death - drug effects; Cytoprotection - drug effects; Depolarization; Destabilization; Development and progression; Diseases; Electron transport chain; Glioma cells; Health aspects; HeLa Cells; Humans; Hydrogen; Hydrogen peroxide; Hydrogen Peroxide - pharmacology; Hypoglycemic agents; Inflammatory diseases; Insulin; Insulin resistance; Kinases; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Medicine and Health Sciences; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mitochondria - chemistry; Mitochondria - drug effects; Mitochondria - metabolism; Oxidation-Reduction - drug effects; Oxidative stress; Oxidative Stress - drug effects; Oximes - pharmacology; Oxygen; Physical Sciences; Piperidines - pharmacology; Prevention; Production processes; Rats; Reactive oxygen species; Reactive Oxygen Species - metabolism; Research and Analysis Methods; Rodents; Superoxides - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0169372

Reactive oxygen species (ROS) play a critical role in the progression of mitochondria-related diseases. A novel insulin sensitizer drug candidate, BGP-15, has been shown to have protective effects in several oxidative stress-related diseases in animal and human studies. In this study, we investigated whether the protective effects of BGP-15 are predominantly via preserving mitochondrial integrity and reducing mitochondrial ROS production. BGP-15 was found to accumulate in the mitochondria, protect against ROS-induced mitochondrial depolarization and attenuate ROS-induced mitochondrial ROS production in a cell culture model, and also reduced ROS production predominantly at the complex I-III system in isolated mitochondria. At physiologically relevant concentrations, BGP-15 protected against hydrogen peroxide-induced cell death by reducing both apoptosis and necrosis. Additionally, it attenuated bacterial lipopolysaccharide (LPS)-induced collapse of mitochondrial membrane potential and ROS production in LPS-sensitive U-251 glioma cells, suggesting that BGP-15 may have a protective role in inflammatory diseases. However, BGP-15 did not have any antioxidant effects as shown by in vitro chemical and cell culture systems. These data suggest that BGP-15 could be a novel mitochondrial drug candidate for the prevention of ROS-related and inflammatory disease progression.