[en] Background : Benfotiamine (BFT) is a synthetic thiamine precursor with high bioavailability. It is efficient in treating complications of type 2 diabetes and has beneficial effects in mouse models of neurodegenerative diseases. The mechanism of action of BFT remains unknown, though it is sometimes suggested that it may be linked to increased thiamine diphosphate (ThDP) coenzyme function. Methods : We used a mouse neuroblastoma cell line (Neuro2a) grown in thiamine-restricted medium. The cells were stressed by exposure to paraquat (PQ) or amyloid 1-42 peptide in the presence or absence of BFT and the cell survival was measured using the MTT method. In each case, BFT was compared with sulbutiamine (SuBT), an unrelated thiamine precursor, and thiamine. Metabolites of BFT were determined by HPLC and mass spectrometry. Results : At 50 μM, BFT protects the cells against PQ and amyloid 1-42 peptide-induced toxicity with the same efficacy. Protective effects were also observed with SuBT and with higher concentrations of thiamine. The main metabolites of BFT were thiamine and S-benzoylthiamine (S-BT). Treatment with both precursors induces a strong increase in intracellular content of thiamine. Protective effects of BFT and SuBT are directly related to thiamine (but not ThDP) levels in Neuro2a cells. Conclusions : BFT, SuBT and thiamine all protect the cells against oxidative stress, suggesting an antioxidant effect of thiamine. Our results are not in favor of a direct ROS scavenging effect of thiamine but rather an indirect effect possibly mediated by some antioxidant signaling pathway. It is however not clear whether this effect is due to thiamine itself, its thiol form or an unknown metabolite. General significance : Our results suggest a role of thiamine in protection against oxidative stress, independent of the coenzyme function of thiamine diphosphate.
Research center :
Giga-Neurosciences - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Sambon, Margaux ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique
NAPP, Aurore ; Centre Hospitalier Universitaire de Liège - CHU > Département de pharmacie hospitalière > Service tarification, gestion des processus et stérilisation
Demelenne, Alice ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments
Fillet, Marianne ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments
Bettendorff, Lucien ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique
Language :
English
Title :
Thiamine and benfotiamine protect neuroblastoma cells against paraquat and ß- amyloid toxicity by a coenzyme-independent mechanism
Publication date :
2019
Journal title :
Heliyon
eISSN :
2405-8440
Publisher :
Elsevier, Netherlands
Volume :
5
Pages :
e01710
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] FRIA - Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture [BE] Fonds Léon Fredericq [BE]
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