Background and purpose: Linalool is one of the main constituents of the essential oil of some aromatic plants, including Lavandula angustifolia. It is used in cosmetics and pharmaceutical industry. In this study, the cytotoxicity and genotoxicity of (±, ) linalool and its naturally occurring enantiomer, (R)-(-) linalool, were evaluated in neuronal PC12 cells. Materials and methods: PC12 cells were incubated with different concentrations of racemate linalool and (R)-(-) linalool for 12 and 24 h. Cytotoxicvity and genotoxicity were evaluated using MTT assay and single cell gel electrophoresis (comet) assay, respectively. Results: Findings showed that (±, ) linalool and (R)-(-) linalool (3200 μ, M) significantly reduced cell viability to 76. 2% and 92%, compared to the control group (untreated cells) (P<0. 001). IC50 values after 12 h and 24 h exposure to (±, ) linalool and (R)-(-) linalool were 2700 µ, M and 5440 µ, M, and 2600 µ, M and 3040 µ, M, respectively. Following treatment by (±, ) linalool or (R)-(-) linalool for 12 or 24 h, the DNA contents in the comets tail, as an indicator of genotoxicity, significantly increased to 21. 36 ±,3. 1%, 27. 6 ±,2. 3% and 15. 2 ±,1. 6% and 21. 3 ±,2%, respectively (P<0. 001). Conclusion: In this study, racemate linalool and its enantiomer, (R)-(-) linalool, decreased the viability of PC12 cells via induction of genotoxicity. (R)-(-) linalool exhibited more cytotoxicity than (±, ) linalool.

The protective effect of an L-type calcium channel blocker, nimodipine, on cell injury induced by oxygen-glucose deprivation (OGD) in PC12 cells was investigated. PC12 cells were exposed to oxygen-glucose deprivation (30 minutes and 60 minutes respectively) in the presence or absence of nimodipine (10mM/L) in three different time schedules (pre-24h, pre-3h and concurrently). Cellular viability was assessed by MTT assay. OGD-induced cell injury was significantly attenuated by nimodipine in all three treatment schedules. Application of MK801 (10mM/L), an antagonist of NMDA glutamate receptors also inhibited PC12 cell death induced by OGD. Our study suggests that nimodipine has protective effects against OGD-induced neurotoxicity.

Objective(s): Nimodipine is an L-type voltage-dependent calcium channel (VDCC) antagonist. However, the actions of nimodipine except calcium blocking are poorly understood. This study aimed to investigate the effect of nimodipine on neurite outgrowth and neuroprotection in vitro. Materials and Methods: After PC12 cells were treated with different concentrations of nimodipine, neurite outgrowth was estimated using the ImageJ software. Neuroprotective effects of nimodipine against H2O2 and calcium ionophore-induced neurotoxicity were investigated using (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. In addition, the activation of extracellular signal-regulated kinase (ERK) and cyclic AMP-response element-binding protein (CREB) pathway was investigated for clarifying the action mechanism of nimodipine. Results: Nimodipine treatment at doses of higher than 10 μ M induced neurite outgrowth in the cells. Additionally, VDCC knockdown by siRNA significantly suppressed the nimodipine-induced neurite outgrowth in PC12 cells, suggesting that the drug promotes neurite outgrowth by binding to VDCC. H2O2 and calcium ionophore induce oxidative and calcium stress in PC12 cells. Nimodipine exhibited neuroprotective effects against H2O2-and calcium ionophore-induced neurotoxicity by increasing the mRNA expression levels of neurotrophic factors, calcium-binding proteins, and antioxidants that are transcribed by CREB activation. Conclusion: This is the first report that nimodipine induces neurite outgrowth and exerts its neuroprotective activity through the ERK/CREB signaling pathway in PC12 cells.