蛋白酪氨酸激酶 (TK) 在细胞各种功能的调节中发挥着关键作用，包括细胞增殖、分化和生长，TK 抑制剂已成为各种癌症的下一代治疗药物。尼罗替尼是用于治疗慢性粒细胞白血病的 TK 抑制剂之一，尽管它能够穿过血脑屏障 (BBB)，但对其对记忆功能的潜在影响却缺乏研究。因此，在本研究中，我们探讨了尼罗替尼对海马依赖性认知功能的影响及其潜在机制。Wistar白化雄性大鼠分为三组，每组10只。 I 组（正常对照）的动物仅接受饮用水，而 II 组和 III 组的动物则以 15 mg/kg 和 30 mg/kg 的剂量口服尼洛替尼治疗。分别每天一次，持续两周。药物治疗完成后，使用 Y 迷宫、新物体识别（NOR）测试和高架十字迷宫（EPM）对动物进行行为测试，以评估认知功能。评估血糖后对动物实施安乐死，解剖海马组织以评估氧化应激标志物。尼罗替尼对 Y 迷宫、NOR 测试和 EPM 的记忆功能造成损害。在不改变血糖水平的情况下，海马组织中谷胱甘肽 (GSH)、丙二醛 (MDA)、Akt、糖原合酶激酶 3 β (GSK3β) 和总抗氧化能力 (TAC) 的显着增加也支持了这些结果。 尼罗替尼治疗通过诱导大鼠海马组织的氧化应激而导致认知功能显着受损。

Protein tyrosine kinases (TKs) play a critical role in the regulation of various functions of a cell, including cellular proliferation, differentiation, and growth, and inhibitors of TKs have emerged as next-generation therapeutic agents in various types of cancer. Nilotinib, one of the TK inhibitors used to treat chronic myeloid leukemia, has been poorly investigated for its potential impact on memory function despite its ability to cross the blood-brain barrier (BBB). Thus, in this study, we investigated the effect of nilotinib on hippocampal-dependent cognitive functions and its potential mechanisms.Wistar albino male rats were divided into three groups of 10 each. The animals of group I (normal control) received drinking water only, while groups II and III were treated with nilotinib at doses of 15 mg/kg and 30 mg/kg, p.o. respectively, once daily for two weeks. The animals were subjected to behavioral tests after completion of drug treatment for the assessment of cognitive function using the Y-maze, novel object recognition (NOR) test, and elevated plus maze (EPM). The animals were euthanized after the estimation of blood glucose, and hippocampal tissues were dissected for the estimation of markers of oxidative stress.Nilotinib produced impairment of memory function on the Y-maze, NOR test, and EPM. These results were also supported by a significant increase in glutathione (GSH), malondialdehyde (MDA), Akt, glycogen synthase kinase-3 beta (GSK3β), and total antioxidant capacity (TAC) in hippocampal tissue without altering the blood glucose level.Nilotinib treatment produced significant impairment of cognitive function by inducing oxidative stress in the hippocampal tissue of rats.