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|Title:||Distribution study of orally administered lipoic acid in rat brain tissues|
|Citation:||Chng, H.T., New, L.S., Neo, A.H., Goh, C.W., Browne, E.R., Chan, E.C.Y. (2009-01-28). Distribution study of orally administered lipoic acid in rat brain tissues. Brain Research 1251 : 80-86. ScholarBank@NUS Repository. https://doi.org/10.1016/j.brainres.2008.11.025|
|Abstract:||Lipoic acid (LA), an essential cofactor for mitochondrial enzymes and a natural antioxidant, has been explored for the treatment of Alzheimer's disease. However, lipoic acid distribution in brain has not been investigated via oral dosing in human subjects or animals. Therefore, we aim to investigate the distribution of orally administered LA from systemic circulation into rat brain tissues and understand the transport efficiency of lipoic acid across the blood-brain barrier. Brain and blood samples were obtained from male Lister Hooded rats at pre-defined time points after single and chronic oral dosing of LA at 50 mg/kg. Levels of LA were determined using liquid chromatography tandem mass spectrometry. An equilibrium dialysis method was employed to elucidate LA protein binding in brain and blood tissues. Basal endogenous levels of LA in control rats were found to fluctuate between 0.005 and 0.267 μM in blood and 0-0.024 μM in brain after correction for residual blood volume. Pharmacokinetic profiling demonstrated rapid biphasic elimination of LA in blood and poor distribution into various brain regions with levels ranging from 0.0009 to 0.0072 μM. The in vitro and in vivo LA brain:blood partition ratios were 0.1 and - 0.01, respectively. Our results demonstrate for the first time that LA does not cross the blood-brain barrier readily and suggest that the antioxidant effect of LA in brain may not be due to its direct effect in the central nervous system. © 2008 Elsevier B.V. All rights reserved.|
|Source Title:||Brain Research|
|Appears in Collections:||Staff Publications|
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