Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi, India.
Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi, India.
Arch Med Res. 2018 Oct;49(7):441-450. doi: 10.1016/j.arcmed.2019.01.004. Epub 2019 Feb 18.
A short branched chain fatty acid, valproic acid (VPA), has been used worldwide for decades in the intervention of seizure disorders, neuropathic pain and migraine. However, several adverse effects of VPA have been reported over the years. The aim of our investigation was to evaluate the adverse effects of VPA on synaptic functions by using synaptosomal preparation of rat brain as an in vitro model and the possible protective role of melatonin against VPA induced neurotoxicity. Melatonin is an antioxidant and scavenger of free radicals secreted by the pineal gland.
In the present investigation, synaptosomes prepared from rat brain were co-treated with melatonin (10 μmol) and VPA (5 mmol) for 2 h under in vitro conditions.
In this study, co-treatment of melatonin with VPA significantly restored the elevated levels of lipid peroxidation (LPO) and protein oxidation. In addition, melatonin prevented VPA induced alterations in non-enzymatic antioxidant defence reduced glutathione (GSH) and activities of synaptosomal integral enzymes such as AChE, Na, K -ATPase and MAO. A significant increase in the generation of reactive oxygen species (ROS) induced by VPA was observed and melatonin ameliorated elevated level of ROS generation. Moreover, the enhanced level of NO and diminished activity of synaptosomal mitochondrial membrane potential was completely prevented by melatonin treatment.
Our results corroborate the use of melatonin as a nutraceutical and mitigatory agent against VPA induced neurotoxicity in brain synaptosomes.
短链支链脂肪酸丙戊酸（VPA）已在全球范围内使用了数十年，用于治疗癫痫发作、神经病理性疼痛和偏头痛。然而，近年来已经报道了 VPA 的几种不良反应。我们的研究目的是通过使用大鼠脑的突触体制剂作为体外模型来评估 VPA 对突触功能的不良反应，以及褪黑素对 VPA 诱导的神经毒性的可能保护作用。褪黑素是一种抗氧化剂，可清除松果腺分泌的自由基。
在本研究中，在体外条件下，用褪黑素（10 μmol）和 VPA（5 mmol）共同处理大鼠脑制备的突触体 2 小时。
在这项研究中，褪黑素与 VPA 的共同处理显著恢复了脂质过氧化（LPO）和蛋白质氧化升高的水平。此外，褪黑素防止了 VPA 诱导的非酶抗氧化防御还原型谷胱甘肽（GSH）和突触体整体酶如乙酰胆碱酯酶、Na+，K+-ATP 酶和 MAO 的活性的改变。观察到 VPA 诱导的活性氧（ROS）的生成显著增加，褪黑素改善了 ROS 生成的升高水平。此外，褪黑素处理完全防止了 NO 水平的升高和突触体线粒体膜电位活性的降低。
我们的结果证实了褪黑素作为一种营养保健品和缓解剂，可用于预防 VPA 诱导的脑突触体神经毒性。
