Neurotoxic effect of statins on mouse neuroblastoma NB2a cell line.
OBJECTIVE
Evidences from cell culture experiments suggest a link between cholesterol and nervous system disease. Statins may have neurotoxic or neuroprotective effects, but these effects remain controversial. Therefore, the present study was aimed to investigate the possible toxicity of statins on a neurite outgrowth in mouse neuroblastoma NB2a cell line.


METHODS
We have utilized d-cAMP-induced terminally differentiated NB2a cells in culture as an experimental model to study the effects of statins. The cell survival and proliferation were studied by MTT. Measurement of neurite outgrowth was done by neurotoxicity screening test. NB2a cell differentiation was achieved by serum free medium plus 0.5 mM dibutyryl cAMP. Cells were incubated for 24 hours at 37 degrees C. After this period, lovastatin, mevastatin and atorvastatin were added to wells at different concentrations (1, 3, 10, 100 microM). Approximately 100 cells were chosen for each sample and examined randomly 24 hours later, from 10 different fields. Total length of neurite was photographed microscopically and measured by image analyze software. Changes in neurite lengths were expressed as % inhibition compared to that of the control group.


RESULTS
Results showed that three statins at high concentrations induced neurite inhibition, inhibited proliferation and reduced the viability of differentiated neuroblastoma NB2a cells.


CONCLUSIONS
Our results suggest that statins could act as a neurotoxic agent at high doses depending upon their concentrations. These results require further investigation at ultra structural and molecular levels to understand long term side effects for clinical safety of statins.
Department of Pharmacology, School of Medicine, Celal Bayar University, Manisa, Turkey. k_vurral@yahoo.com.tr
K
K
Vural
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MI
Tuğlu
D000818:Animals; D000069059:Atorvastatin; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006538:Heptanoic Acids / Q000633:toxicity; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000633:toxicity*; D008148:Lovastatin / Q000031:analogs & derivatives / Q000633:toxicity; D051379:Mice; D016501:Neurites / Q000187:drug effects* / Q000473:pathology; D009447:Neuroblastoma / Q000473:pathology*; D011758:Pyrroles / Q000633:toxicity
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; C012258:mevastatin; D008148:Lovastatin; D000069059:Atorvastatin