Thymoquinone (TQ) exhibits a wide spectrum of biological activities. Most studies on the neurotoxic action of TQ have been carried out in cancer cell lines. Here, we studied the toxic effect of TQ in primary neuronal cultures in vitro. Incubation with 0.04-0.05 mM TQ for 24 h induced the death of cultured cerebellar granule neurons (CGNs) in a dose dependent manner. Neuronal death was preceded by an increase in the reactive oxygen species (ROS) generation, as demonstrated using CellROX Green and MitoSOX Red. Confocal and electron microscopy showed that incubation with 0.05 mM TQ for 5 h induced changes in the intracellular localization of mitochondria and mitochondria hypertrophy and cell swelling. The antioxidant N-acetyl-L-cysteine (2 mM) protected CGNs from the toxic action of TQ. Taken together, these facts suggest that TQ is toxic for normal neurons, while ROS-induced changes in the mitochondria can be one of the major causes of the TQ-induced neuronal damage and death.

中文翻译：

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百里醌诱导小脑颗粒神经元的线粒体损伤和死亡

百里醌 (TQ) 具有广泛的生物活性。大多数关于 TQ 神经毒性作用的研究都是在癌细胞系中进行的。在这里，我们研究了 TQ 在体外原代神经元培养物中的毒性作用。用 0.04-0.05 mM TQ 孵育 24 小时以剂量依赖性方式诱导培养的小脑颗粒神经元 (CGN) 死亡。正如使用 CellROX Green 和 MitoSOX Red 所证明的那样，神经元死亡之前会增加活性氧 (ROS) 的生成。共聚焦和电子显微镜显示，与 0.05 mM TQ 孵育 5 小时会诱导线粒体的细胞内定位发生变化，以及线粒体肥大和细胞肿胀。抗氧化剂 N-乙酰-L-半胱氨酸 (2 mM) 保护 CGN 免受 TQ 的毒性作用。综合起来，