Folda Alessandra, Scalcon Valeria, Tonolo Federica, Rigobello Maria Pia, Bindoli Alberto
Department of Biomedical Sciences, University of Padova, Padova, Italy.
Department of Comparative Biomedicine and Food Science, University of Padova, Legnaro, Italy.
Biofactors. 2025 Jan-Feb;51(1):e2121. doi: 10.1002/biof.2121. Epub 2024 Sep 20.
Thiamine (vitamin B1), under the proper conditions, is able to reversibly open the thiazole ring, forming a thiol-bearing molecule that can be further oxidized to the corresponding disulfide. To improve the bioavailability of the vitamin, several derivatives of thiamine in the thioester or disulfide form were developed and extensively studied over time, as apparent from the literature. We have examined three thiamine-derived disulfides: thiamine disulfide, sulbutiamine, and fursultiamine with reference to their intervention in modulating the thiol redox state. First, we observed that both glutathione and thioredoxin (Trx) systems were able to reduce the three disulfides. In particular, thioredoxin reductase (TrxR) reduced these disulfides either directly or in the presence of Trx. In Caco-2 cells, the thiamine disulfide derivatives did not modify the total thiol content, which, however, was significantly decreased by the concomitant inhibition of TrxR. When oxidative stress was induced by tert-butyl hydroperoxide, the thiamine disulfides exerted a protective effect, indicating that the thiol form deriving from the reduction of the disulfides might be the active species. Further, the thiamine disulfides examined were shown to increase the nuclear levels of the transcription factor nuclear factor erythroid 2 related factor 2 and to stimulate both expression and activity of NAD(P)H quinone dehydrogenase 1 and TrxR. However, other enzymes of the glutathione and Trx systems were scarcely affected. As the thiol redox balance plays a critical role in oxidative stress and inflammation, the information presented can be of interest for further research, considering the potential favorable effect exerted in the cell by many sulfur compounds, including the thiamine-derived disulfides.
硫胺素（维生素B1）在适当条件下能够可逆地打开噻唑环，形成一个含硫醇的分子，该分子可进一步氧化为相应的二硫化物。为提高该维生素的生物利用度，随着时间的推移，人们开发并广泛研究了硫酯或二硫化物形式的几种硫胺素衍生物，这从文献中可以明显看出。我们研究了三种硫胺素衍生的二硫化物：二硫化硫胺素、舒布硫胺和呋喃硫胺对调节硫醇氧化还原状态的干预作用。首先，我们观察到谷胱甘肽和硫氧还蛋白（Trx）系统都能够还原这三种二硫化物。特别是，硫氧还蛋白还原酶（TrxR）可直接或在Trx存在的情况下还原这些二硫化物。在Caco-2细胞中，硫胺素二硫化物衍生物并未改变总硫醇含量，然而，TrxR的同时抑制会使其显著降低。当用叔丁基过氧化氢诱导氧化应激时，硫胺素二硫化物发挥了保护作用，这表明由二硫化物还原产生的硫醇形式可能是活性物质。此外，所研究的硫胺素二硫化物显示可增加转录因子核因子红细胞2相关因子2的核水平，并刺激NAD(P)H醌脱氢酶1和TrxR的表达及活性。然而，谷胱甘肽和Trx系统的其他酶几乎未受影响。由于硫醇氧化还原平衡在氧化应激和炎症中起关键作用，考虑到包括硫胺素衍生的二硫化物在内的许多含硫化合物在细胞中发挥的潜在有利作用，本文提供的信息可能对进一步研究有意义。
