Chaudhary Shaista, Parvez Suhel
Department of Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India.
ACS Omega. 2022 Oct 20;7(43):38269-38276. doi: 10.1021/acsomega.2c00163. eCollection 2022 Nov 1.
Valproic acid (VPA) is short branched-chain fatty acid (BCFA) derived from valeric acids which are naturally produced by (flowering plant). Neurotoxicity caused by BCFA-like VPA may be mediated by oxidative stress, according to research involving the cerebral cortex and cerebellum. In the present study, we explored the possible protective effect of different antioxidants such as melatonin, quercetin, and piperine on VPA exposure by using a supernatant preparation of the cerebral cortex and cerebellum regions of the rat brain. The present study revealed that melatonin, quercetin, and piperine significantly prevented VPA-induced oxidative stress in the cerebral cortex and cerebellum regions. VPA was also observed to lower the level of reduced glutathione, and this effect was significantly mitigated by these antioxidants. Melatonin, quercetin, and piperine also ameliorated and altered the activities of AChE, Na, KATPase, and MAO in the cerebral cortex and cerebellum. Results of this study also suggest that prior treatment of antioxidants like melatonin, quercetin, and piperine helps in combating the oxidative stress induced by VPA in the cerebral cortex and cerebellum region of the rat brain. Thus, sufficient dietary intake of these antioxidants by individuals at high risk of VPA exposure could prove beneficial in combating the adverse effect of VPA.
丙戊酸(VPA)是一种短链支链脂肪酸(BCFA),由缬草酸衍生而来,缬草酸是(开花植物)自然产生的。根据一项涉及大脑皮层和小脑的研究,类似VPA的BCFA引起的神经毒性可能由氧化应激介导。在本研究中,我们通过使用大鼠大脑皮层和小脑区域的上清液制剂,探讨了褪黑素、槲皮素和胡椒碱等不同抗氧化剂对VPA暴露的可能保护作用。本研究表明,褪黑素、槲皮素和胡椒碱显著预防了VPA诱导的大脑皮层和小脑区域的氧化应激。还观察到VPA降低了还原型谷胱甘肽水平,而这些抗氧化剂显著减轻了这种作用。褪黑素、槲皮素和胡椒碱还改善并改变了大脑皮层和小脑中乙酰胆碱酯酶、钠钾ATP酶和单胺氧化酶的活性。本研究结果还表明,预先使用褪黑素、槲皮素和胡椒碱等抗氧化剂有助于对抗VPA在大鼠大脑皮层和小脑区域诱导的氧化应激。因此,VPA暴露风险高的个体通过饮食充分摄入这些抗氧化剂可能有助于对抗VPA的不良反应。