gms | German Medical Science

Objective: During surgery, cells of the nervous system (NS) are exposed to various stressors, which can lead to consequential damage to nerve tissue. So far, there is little knowledge about neuroprotective substances that can prevent surgically induced nerve damage. Thiamine (TM) is an essential coenzyme in energy metabolism and the deficiency reduce conduction speed in neuronal cells and can lead to Wernicke Encephalopathy. In addition, an anti-apoptotic function of TM has been described before. Therefore, the aim of study was to investigate the neuroprotective influence of different TM derivatives and the associated anti-apoptotic cellular mechanisms.

Methods: Immortalized Schwann (SW10) and neuronal cells (RN33B) were seeded and four hours pre-treated with 10 µM thiamine hydrochloride (TIH), 5 µM sulbuthiamine (SBT), 5 µM dibenzoylthiamine (DBT) or 5µM benfothiamine (BFT). Then the cells were stressed with 150mM NaCl (osmotic stress (OMS)) or 2% Ethanol (oxidative stress (OXS)). After 24 hours, the cellular release of lactate dehydrogenase (LDH) was measured. The LDH release of total lysed cells was set to 100%. Proteins of treated and untreated cells were separated using SDS-PAGE. In western blot analysis, the amount of total and phosphorylated protein of AKT(Ser473), CREB(Ser133), and ERK1(Tyr 202) and ERK2(Tyr204) was investigated.

Results: Under TIH treatment, reduced cell death was measured in neuronal and Schwann cells during OXS. According to western blot analysis, treatment with TIH resulted in increased amount and phosphorylation of CREB(Ser133) in SW10 cells during OMS. After treatment with SBT, reduced LDH release was observed in Schwann cells during OXS, which was associated with an increased ERK1 and ERK2 protein level. Treatment with DBT reduced LDH release in Schwann cells during OMS and also led to an increase ERK1 and ERK2 protein level. Under BFT treatment, reduced LDH release was measured in SW10 cells during OSM. In the same time the total amount and phosphorylation of AKT(Ser473) was increased.

Conclusion: The measured cell death reduction in a surgical-like stress model suggests that TM and its derivatives may have a beneficial effect on the survival of NS cells by associated increased levels and activation of anti-apoptotic proteins. The influence of TM on these and other anti-apoptotic proteins should be further investigated.