Valproic acid (VPA)-a short branched chain fatty acid (BCFA), is widely recognized as an anticonvulsant and a mood-stabilizing drug, but various adverse effects of VPA have also been investigated. However, the impact of BCFAs aggregation on brain cells, in the pathogenesis of neurodegeneration remains elusive. The objective of this study is to understand the cellular mechanisms underlying VPA-induced neuronal cell death mediated by oxidative stress, and the neuroprotective role of exogenous melatonin treatment on VPA-induced cell death. Neurotoxicity of VPA and protective role exerted by melatonin were assessed in vitro in SH-SY5Y cells and in vivo in the cerebral cortex and cerebellum regions of Wistar rat brain. The results show that melatonin pre-treatment protects the cells from VPA-induced toxicity by exerting an anti-apoptotic and anti-inflammatory effect by regulating apoptotic proteins and pro-inflammatory cytokines. The findings of the present study emphasize novel insights of melatonin as a supplement for the prevention and treatment of neuronal dysfunction induced by VPA.

中文翻译：

---

褪黑激素减弱支链脂肪酸诱导的细胞凋亡介导的神经变性

丙戊酸 (VPA) - 一种短支链脂肪酸 (BCFA)，被广泛认为是一种抗惊厥药和一种稳定情绪的药物，但 VPA 的各种不良反应也已被研究。然而，BCFAs 聚集对脑细胞的影响，在神经变性的发病机制中仍然难以捉摸。本研究的目的是了解氧化应激介导的 VPA 诱导的神经元细胞死亡的细胞机制，以及外源性褪黑激素治疗对 VPA 诱导的细胞死亡的神经保护作用。VPA 的神经毒性和褪黑激素发挥的保护作用在 SH-SY5Y 细胞中进行了体外评估，在 Wistar 大鼠大脑的大脑皮层和小脑区域进行了体内评估。结果表明，褪黑激素预处理通过调节凋亡蛋白和促炎细胞因子发挥抗凋亡和抗炎作用，从而保护细胞免受 VPA 诱导的毒性。本研究的结果强调了褪黑激素作为预防和治疗 VPA 诱导的神经元功能障碍的补充剂的新见解。