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 H2O2-induced oxidative stress. SK–N–SH cells treated with H2O2 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 H2O2 for 24h, nitrite generation was increased by twice compared with 2h. Galantamine treatment resulted in a significant inhibition of H2O2-induced nitrite generation whatever the concentration tested with a return to control values. Galantamine also concentration-dependently inhibited AChE activity (28–88%) in H2O2–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.