The effect of conventional and sustained delivery of levodopa on SH-SY5Y neuroblastoma cells.
L-dihydroxyphenylalanine-(L-dopa) has been used for the treatment of Parkinson's disease for decades. Recently it has been shown that L-dopa, at concentrations of 0.25 x 10(4) M or larger, can be toxic for human neuroblastoma cells. Toxicity has been associated with the productions of high levels of quinones. The reactive oxygen or nitrogen species generated in the enzymatical oxidation or auto-oxidation of an excess amount of dopamine or L-dopa induce neuronal damage and/or apoptotic or non-apoptotic cell death. The objective of this study was to investigate if the delivery method could reduce the toxicity associated with higher levels of L-dopa. SH-SY5Y neuroblastoma cells were challenged with a bolus administration of 5, 50, 100 or 500 microM of L-dopa or a sustained delivery of L-dopa to release the desired concentrations by the end of one incubation period. The cells were incubated for periods of 24, 48 or 72 hours, and at the end of each phase cell number, cell morphology, and cellular glutathione levels were determined. Conventional administration of L-dopa showed reductions in cell number at 72 hours in cells treated with 50 and 500 microM L-dopa. A similar trend was observed using drug delivery administration of L-dopa. Glutathione levels were reduced in the treatment groups after 24 hours and showed recovery by 48 hours. Morphologic evaluation revealed that the lower dose groups appeared similar to control in both conventional and drug delivery whereas cellular distortion was observed at higher doses regardless of delivery method.


CONCLUSIONS
Lower dose L-dopa was demonstrated to be less cytotoxic in SH-SY5Y neuroblastoma cells in both conventional and sustained drug delivery methods.
Martin
Tina Mitchell
TM
University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
Benghuzzi
Hamed
H
Tucci
Michelle
M
D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage* / Q000009:adverse effects*; D009447:Neuroblastoma / Q000473:pathology* / Q000503:physiopathology*
D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D007980:Levodopa