دورية أكاديمية

Thiamine and benfotiamine protect neuroblastoma cells against paraquat and β-amyloid toxicity by a coenzyme-independent mechanism.

التفاصيل البيبلوغرافية
العنوان: Thiamine and benfotiamine protect neuroblastoma cells against paraquat and β-amyloid toxicity by a coenzyme-independent mechanism.
المؤلفون: Sambon M; Laboratory of Neurophysiology, GIGA-Neurosciences, University of Liège, Liège, Belgium., Napp A; Laboratory for the Analysis of Medicines, CIRM, Department of Pharmacy, University of Liège, Liège, Belgium., Demelenne A; Laboratory for the Analysis of Medicines, CIRM, Department of Pharmacy, University of Liège, Liège, Belgium., Vignisse J; Laboratory of Neurophysiology, GIGA-Neurosciences, University of Liège, Liège, Belgium., Wins P; Laboratory of Neurophysiology, GIGA-Neurosciences, University of Liège, Liège, Belgium., Fillet M; Laboratory for the Analysis of Medicines, CIRM, Department of Pharmacy, University of Liège, Liège, Belgium., Bettendorff L; Laboratory of Neurophysiology, GIGA-Neurosciences, University of Liège, Liège, Belgium.
المصدر: Heliyon [Heliyon] 2019 May 14; Vol. 5 (5), pp. e01710. Date of Electronic Publication: 2019 May 14 (Print Publication: 2019).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Ltd Country of Publication: England NLM ID: 101672560 Publication Model: eCollection Cited Medium: Print ISSN: 2405-8440 (Print) Linking ISSN: 24058440 NLM ISO Abbreviation: Heliyon Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: London : Elsevier Ltd, [2015]-
مستخلص: 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 β 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 β 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.
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فهرسة مساهمة: Keywords: ARE, antioxidant response element; BFT, benfotiamine; Cell biology; FBS, fetal bovine serum; Neuroscience; O-BT, O-benzoylthiamine; PQ, paraquat; ROS, reactive oxygen species; S-BT, S-benzoylthiamine; SuBT, sulbutiamine; TPK, thiamine pyrophosphokinase; ThDP, thiamine diphosphate; ThMP, thiamine monophosphate
تواريخ الأحداث: Date Created: 20190614 Latest Revision: 20220408
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC6520661
DOI: 10.1016/j.heliyon.2019.e01710
PMID: 31193162
قاعدة البيانات: MEDLINE
الوصف
تدمد:2405-8440
DOI:10.1016/j.heliyon.2019.e01710