Antioxidative properties of galantamine on neuronal damage induced by hydrogen peroxide in SK-N-SH cells.
Galantamine, an acetylcholinesterase inhibitor used to enhance memory in AD patients by acetylcholinesterase inhibition, has been tested for its protective properties on an in vitro model of H(2)O(2)-induced oxidative stress. SK-N-SH cells treated with H(2)O(2) for 2h showed an increase in ROS production (54%) and in NO production (52%) together with a marked reduction of the mitochondrial membrane potential (19%). These features, typical of the oxidative injury that accompanies AD, were partly recovered by galantamine. Galantamine reduced the release of reactive oxygen species (up to 50%) and prevented loss in mitochondrial activity. When SK-N-SH cells were treated with H(2)O(2) for 24h, nitrite generation was increased by twice compared with 2h. Galantamine treatment resulted in a significant inhibition of H(2)O(2)-induced nitrite generation whatever the concentration tested with a return to control values. Galantamine also concentration-dependently inhibited AChE activity (28-88%) in H(2)O(2)-SK-N-SH cells after 24h. This drug, which facilitates cholinergic neurotransmission, is also neuroprotective by lowering oxidative injury. Our study provides a better understanding of the mechanisms of protection of this acetylcholinesterase inhibitor which also has antioxidative properties.
Ezoulin
Miezan J M
MJ
Unité de Pharmacochimie Moléculaire et Systèmes Membranaires (EA2381), Université Paris 7-Denis Diderot, 75251 Paris Cedex 05, France.
Ombetta
Jean-Edouard
JE
Dutertre-Catella
Hélène
H
Warnet
Jean-Michel
JM
Massicot
France
F
D000110:Acetylcholinesterase / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D005702:Galantamine / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D016877:Oxidants; D017382:Reactive Oxygen Species; D005702:Galantamine; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D000110:Acetylcholinesterase