The effect of acetylcholine administration to sh-sy5y cells in the presence of levodopa (L-dopa) using conventional and sustained drug delivery - biomed 2010.
The purpose of the study was to evaluate the effects of conventional and sustained delivery of levodopa (L-dopa) alone or in combination with acetylcholine in SH-SY5Y neuroblastoma cells. The loss of dopaminergic neurons resulting in an imbalance between dopamine and acetylcholine is a hallmark feature of Parkinson disease. L-dopa has been shown to potentiate D2 receptor-mediated effects and inhibits acetylcholine release in Parkinson disease. According to the literature, conventionally administered L-dopa is short-lived and oxidized to metabolites which are neurotoxic and lead to a further decline in dopaminergic neurons. In addition, most in vitro studies do not taken into account that acetylcholine is elevated in vivo. SH-SY5Y cells were conventionally administered or in a sustained manner L-dopa, acetylcholine, or a combination of acetycholine and L-dopa for periods of 24, 48 and 72 hours, and evaluated for cell proliferation, cell viability, cellular damage, nitric oxide production, cellular glutathione levels, and hydrogen peroxide production. Overall, sustained delivery of L-dopa alone or in combination with acetylcholine showed decreases in cell number which were 50% less than those seen by conventional administration of the compounds within the first 48 hours of culture. However, regardless of administration of L-dopa alone or in combination with acetylcholine there were increases in cellular levels of MDA, nitric oxide, and hydrogen peroxide. Interestingly, the increases seen in the sustained delivery of L-dopa were less than those seen with conventional administration. In addition, the increased levels of the aforementioned parameters were delayed by 24 hours compared with conventional administration of these compounds. Appearances of the culture media following sustained delivery show increased in oxidized L-dopa. It is more than likely that the decreases in cell number and increased levels of nitric oxide, hydrogen peroxide, and MDA are a direct result of the oxidized metabolites of L-dopa.
Mitchell Martin Phd
Tina
T
University of Mississippi Medical Center, MS.
Benghuzzi Ph D
Hamed
H
Tucci Ph D
Michelle
M