Mallika B, Sudha K, Massand A, Murlimanju B V, Sonal G, Neelam M P, Sowndarya K
Department of Biochemistry, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Karnataka, Manipal, 576104, India.
Department of Anatomy, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Karnataka, Manipal, 576104, India.
Clin Ter. 2025 Mar-Apr;176(2):127-135. doi: 10.7417/CT.2025.5195.
Thiamine deficiency mimics the features of Alzheimer's disease (AD) like cognitive impairment, amyloid and tau deposition. There is growing evidence that links AD with aluminium. The study aims to explore the effect of benfotiamine (BFT), a lipid soluble thiamine derivative, on aluminium induced AD rat model.
All the rats except control group were administered AlCl3 for one month to induce dementia. Positive control group received donepezil; BFT groups received 50 and 300 mg/kg b.w. /day for last 15 days. Morris water maze test was performed to assess learning and memory. Histological changes were studied in C3 region of hippocampus. Acetylcholine esterase (AChE), malondialdehyde, reduced glutathione, nitric oxide, hyperphosphorylated tau proteins and caspase 8 were estimated in brain homogenate.
AlCl3 impaired learning and memory significantly and increased AChE, caspase 8, tau proteins. The decrease in NO level was highly significant (p<0.001) in BFT treated rats compared to control. Lower dose of BFT had profound influence on augmenting GSH levels (p=0.012). Further, higher dose of BFT improved learning and memory significantly in AD model (p=0.009) and was more effective in preventing taupathy, apoptosis and neuronal damage by acting as a potent antioxidant.
It can be concluded that oral supplementation of 300mg /kg b.w. /day of BFT may reverse AD pathological processes and improve dementia. However, the need of thiamine supplementation in elderly persons to delay or halt the cognitive loss and eventual dementia needs validation by clinical trial.
硫胺素缺乏会表现出类似阿尔茨海默病(AD)的特征,如认知障碍、淀粉样蛋白和tau蛋白沉积。越来越多的证据将AD与铝联系起来。本研究旨在探讨脂溶性硫胺素衍生物苯磷硫胺(BFT)对铝诱导的AD大鼠模型的影响。
除对照组外,所有大鼠均给予氯化铝1个月以诱导痴呆。阳性对照组给予多奈哌齐;BFT组在最后15天分别给予50和 300 mg/kg体重/天的剂量。进行莫里斯水迷宫试验以评估学习和记忆能力。对海马体C 3区域进行组织学变化研究。测定脑匀浆中的乙酰胆碱酯酶(AChE)、丙二醛、还原型谷胱甘肽、一氧化氮、过度磷酸化的tau蛋白和半胱天冬酶8。
氯化铝显著损害学习和记忆能力,并增加AChE、半胱天冬酶8和tau蛋白。与对照组相比,BFT处理的大鼠一氧化氮水平的降低非常显著(p<0.001)。较低剂量的BFT对提高谷胱甘肽水平有深远影响(p=0.0 12)。此外,较高剂量的BFT在AD模型中显著改善了学习和记忆能力(p=0.009),并且作为一种有效的抗氧化剂,在预防tau病变、细胞凋亡和神经元损伤方面更有效。
可以得出结论,口服300mg/kg体重/天的BFT可能会逆转AD的病理过程并改善痴呆症状。然而,老年人补充硫胺素以延迟或阻止认知能力丧失和最终痴呆的必要性需要通过临床试验来验证。