Antioxidative properties of galantamine on neuronal damage induced by hydrogen peroxide in SK–N–SH cells

Abstract

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 2O 2-induced oxidative stress. SK–N–SH cells treated with H 2O 2 for 2 h 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 2O 2 for 24 h, nitrite generation was increased by twice compared with 2 h. Galantamine treatment resulted in a significant inhibition of H 2O 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 2O 2–SK–N–SH cells after 24 h. 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.