Dibenzoylthiamine, a lipophilic thiamine precursor, protects against oxidative damage in neuroblastoma cells

Recent evidence suggests that thiamine (vitamin B1) and some of its derivatives can exert prominent neuroprotective effects in the mammalian brain, particularly in mouse models of Alzheimer’s disease and tauopathies. As orally administered thiamine crosses intestinal and blood-brain barriers only slowly, precursors with higher bioavailability e.g. sulbutiamine, benfotiamine and dibenzoylthiamine, have been developed. We investigated the protective effects of thiamine and those precursors in neuroblastoma cells cultured in a medium containing minimal amounts of thiamine (10 nM), but sufficient to sustain normal growth. We induced oxidative stress by incubating the cells (24 h) in the presence of the neurotoxic agent paraquat (0.25 mM). This treatment reduced cell viability by 40%. When thiamine or the precursors were present simultaneously, we observed protective effects by the precursors while free thiamine was ineffective. Dibenzoylthiamine was most efficient, affording complete protection of cells at 10-20 µM. It also caused the highest increase in intracellular thiamine, suggesting that the protection from oxidative damage is linked to increased levels of free thiamine (rather than thiamine disphophate) in the neuroblastoma cells. The mechanism of this protective effect is presently under investigation. These results and others from our laboratory raise the possibility that dibenzoylthiamine might useful as a neuroprotective agent in neurodegenerative disease.