Mitochondrial medicine: neuroprotection and life extension by the new amphiphilic nitrone LPBNAH acting as a highly potent antioxidant agent.
The search for effective treatments that prevent oxidative stress associated with premature ageing and neurodegenerative diseases is an important area of neurochemical research. As age- and disease-related oxidative stress is frequently associated with mitochondrial dysfunction, amphiphilic antioxidant agents of high stability and selectivity that target these organelles can provide on-site protection. Such an amphiphilic nitrone protected human neuroblastoma cells at low micromolar concentrations against oxidative damage and death induced by exposure to the beta-amyloid peptide, hydrogen peroxide and 3-hydroxykynurenine. Daily administration of the antioxidant at a concentration of only 5 mum significantly increased the lifespan of the individually cultured rotifer Philodina acuticornis odiosa Milne. This compound is unique in its exceptional anti-ageing efficacy, being one order of magnitude more potent than any other compound previously tested on rotifers. The nitrone protected these aquatic animals against the lethal toxicity of hydrogen peroxide and doxorubicin and greatly enhanced their survival when co-administered with these oxidotoxins. These findings indicate that amphiphilic antioxidants have a great potential as neuroprotective agents in preventing the death of cells and organisms exposed to enhanced oxidative stress and damage.
Poeggeler
Burkhard
B
Abteilung fuer Stoffwechselphysiologie, Institut fuer Zoologie, Anthropologie und Entwicklungsbiologie der Georg August Universitaet Goettingen, Goettingen, Germany. bpoegge@gwdg.de
Durand
Grégory
G
Polidori
Ange
A
Pappolla
Miguel A
MA
Vega-Naredo
Ignacio
I
Coto-Montes
Ana
A
Böker
Jutta
J
Hardeland
Rüdiger
R
Pucci
Bernard
B
D000375:Aging / Q000187:drug effects / Q000502:physiology; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003952:Diagnostic Imaging / Q000379:methods; D004187:Disaccharides / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007097:Imines / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D008017:Life Expectancy; D028361:Mitochondrial Diseases / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D009589:Nitrogen Oxides / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D012403:Rotifera / Q000187:drug effects
D016229:Amyloid beta-Peptides; D004187:Disaccharides; D007097:Imines; C514717:LPBNAH compound; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; C015388:nitrones; D006861:Hydrogen Peroxide