Neuroprotective effect of (R)-(-)-linalool on oxidative stress in PC12 cells

Background: Oxidative stress plays an important role in neurodegeneration, pain and inflammation. (R)-(-)-linalool (LIN) is endowed with neuroprotective, anti-nociceptive and anti-inflammatory properties. Purpose: The present study aims at investigating the hypothesis that LIN's neuroprotective, antinociceptive and anti-inflammatory properties descend from its ability to act as antioxidant. The study challenges this hypothesis by verifying whether LIN may counteract hydrogen peroxide (H2O2)-induced oxidative stress in PC12 cells. Methods: In H2O2-exposed PC12 cells, LIN was tested on a) cell viability, measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), b) damage of plasma membrane, measured by lactate dehydrogenase (LDH) release, c) intracellular levels of reactive-oxygen-species (ROS), d) apoptosis and e) cell cycle distribution. Results: Under H2O2-induced cell viability reduction, LIN protects PC12 cells. Likewise, LIN protects cells from oxidative damage by preventing the H2O2-dependent increase of LDH release, counteracts intracellular ROS overproduction and reduces H2O2-induced apoptosis. Finally, the results of the cell cycle analysis from cells exposed to H2O2 indicate that LIN incubation reduces the number of cells induced into quiescence by H2O2 in the G2/M phase. Conclusions: These findings indicate that LIN protects PC12 cells from H2O2-induced oxidative stress. This mechanism could justify the neuroprotective, anti-nociceptive and anti-inflammatory effects of this compound and suggest LIN as a potential therapeutic agent for the management oxidative stress-mediated pain.