Montelukast is a cysteinyl leukotriene (CysLT) receptor antagonist with efficacy against a variety of diseases, including asthma and inflammation-related conditions. However, various neuropsychiatric events (NEs) suspected to be related to montelukast have been reported recently, with limited understanding on their association and underlying mechanisms. This study aimed to investigate whether montelukast can induce neuroinflammation and neurotoxicity in microglial HAPI cells and neural SH-SY5Y cells. The present study also compared the effects of montelukast with a 5-lipoxygenase inhibitor (zileuton) and a cyclooxygenase-2 inhibitor (celecoxib) to better understand modulation of related pathways. HAPI or SH-SY5Y cells were treated with the indicated drugs (3.125 μM–100 μM) for 24 h to investigate drug-induced neuroinflammation and neurotoxicity. Montelukast induced cytotoxicity in HAPI cells (50–100 μM), accompanied with caspase-3/7 activation, prostaglandin E₂ (PGE₂) release, and reactive oxygen species (ROS) production. Whilst both montelukast and zileuton down-regulated CysLT release in HAPI cells, zileuton did not significantly affect cell viability or inflammatory and oxidative factors. Celecoxib decreased HAPI cell viability (6.25–100 μM), accompanied with increasing caspase-3/7 activation and ROS production, but in contrast to montelukast increased CysLT release and decreased PGE₂ production. Similar to observations in HAPI cells, both montelukast and celecoxib (50–100 μM) but not zileuton produced toxicity in SH-SY5Y neuroblastoma cells. Similarly, CM from HAPI cells treated with either montelukast or zileuton produced toxicity in SH-SY5Y cells. The results of the current study show the capability of montelukast to directly induce toxicity and inflammation in HAPI cells, possibly through the involvement of PGE₂ and ROS, and toxicity in undifferentiated SH-SY5Y neuroblastoma cells. The current study highlights the importance of consideration between benefit and risk of montelukast usage and provides references for future investigation on decreasing montelukast-related NEs.

孟鲁司特是一种半胱氨酰白三烯（CysLT）受体拮抗剂，对多种疾病（包括哮喘和炎症相关疾病）具有功效。然而，最近已经报道了各种怀疑与孟鲁司特有关的神经精神事件（NEs），但对其关联性和潜在机制的了解有限。这项研究旨在调查孟鲁司特是否可以在小胶质HAPI细胞和神经SH-SY5Y细胞中诱导神经炎症和神经毒性。本研究还比较了孟鲁司特与5-脂氧合酶抑制剂（齐留通）和环氧合酶-2抑制剂（塞来昔布）的作用，以更好地了解相关途径的调节作用。将HAPI或SH-SY5Y细胞用指定的药物（3.125 μM–100μM）处理24小时，以研究药物诱导的神经炎症和神经毒性。₂（PGE ₂）释放，并产生活性氧（ROS）。尽管孟鲁司特和齐留通都下调了HAPI细胞中的CysLT释放，但齐留通并未显着影响细胞活力或炎症和氧化因子。塞来昔布降低HAPI细胞活力（6.25–100μM），并伴有caspase-3 / 7激活和ROS产生增加，但与孟鲁司特相反，CysLT释放增加而PGE ₂减少生产。与HAPI细胞中的观察结果相似，孟鲁司特和塞来昔布（50–100μM）对齐留通没有作用，但对SH-SY5Y神经母细胞瘤细胞产生毒性。同样，用孟鲁司特或齐留通处理过的HAPI细胞中的CM在SH-SY5Y细胞中产生毒性。当前研究的结果表明孟鲁司特具有直接诱导HAPI细胞毒性和炎症的能力，可能是通过PGE ₂和ROS的参与，以及未分化的SH-SY5Y神经母细胞瘤细胞的毒性。本研究强调了孟鲁司特使用的益处和风险之间进行考虑的重要性，并为今后研究减少孟鲁司特相关的NE提供了参考。