Reference : Dibenzoylthiamine has powerful antioxidant and anti-inflammatory properties in cultur...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/251599
Dibenzoylthiamine has powerful antioxidant and anti-inflammatory properties in cultured cells and in mouse models of stress and neurodegeneration
English
Sambon, Margaux mailto [Université de Liège - ULiège > > GIGA >]
Gorlova, Anna [> >]
Demelenne, Alice mailto [Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments >]
Alhama-Riba, Judit [> >]
Coumans, Bernard mailto [Université de Liège - ULiège > > Stem Cells-Molecular Regulation of Neurogenesis >]
Lakaye, Bernard mailto [Université de Liège - ULiège > > Stem Cells-Molecular Regulation of Neurogenesis >]
Wins, Pierre [> >]
Fillet, Marianne mailto [Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments >]
Anthony, Daniel C. [> >]
Strekalova, Tatyana [> >]
Bettendorff, Lucien mailto [Université de Liège - ULiège > > Neurosciences-Neurophysiology >]
In press
Biomedicines
MDPI AG
Yes (verified by ORBi)
International
2227-9059
Switzerland
[en] thiamine ; oxidative stress ; inflammation ; neurodegeneration ; animal model ; amyotrophic lateral sclerosis ; paraquat ; lipopolysaccharide ; benfotiamine ; sulbutiamine ; dibenzoylthiamine
[en] Thiamine precursors, the most studied being benfotiamine (BFT), have protective effects in mouse models of neurodegenerative diseases. BFT decreased oxidative stress and inflammation, two major characteristics of neurodegenerative diseases, in a neuroblastoma cell line (Neuro2a) and an immortalized brain microglial cell line (BV2). Here, we tested the potential antioxidant and anti-inflammatory effects of the hitherto unexplored derivative O,S-dibenzoylthiamine (DBT) in these two cell lines. We show that DBT protects Neuro2a cells against paraquat (PQ) toxicity by counteracting oxidative stress at low concentrations and increases the synthesis of reduced glutathione and NADPH in a Nrf2-independent manner. In BV2 cells activated by lipopolysaccharides (LPS), DBT significantly decreased inflammation by suppressing translocation of NF-κB to the nucleus. Our results also demonstrate the superiority of DBT over thiamine and other thiamine precursors, including BFT, in all of the in vitro models. Finally, we show that the chronic administration of DBT arrested motor dysfunction in FUS transgenic mice, a model of amyotrophic lateral sclerosis, and it reduced depressive-like behavior in a mouse model of ultrasound-induced stress in which it normalized oxidative stress marker levels in the brain. Together, our data suggest that DBT may have therapeutic potential for brain pathology associated with oxidative stress and inflammation by novel, coenzyme-independent mechanisms.
Giga-Neurosciences ; Centre Interdisciplinaire de Recherche sur le Médicament - CIRM
Fonds de la Recherche Scientifique - F.R.S.-FNRS ; Fonds Léon Fredericq ; “5–100” Russian Research Excellence ; Fonds pour la formation à la Recherche dans l'Industrie et dans l'Agriculture (Communauté française de Belgique) - FRIA
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/251599

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