Ellagic acid attenuates arsenic induced neuro-inflammation and mitochondrial dysfunction associated apoptosis.
Ellagic acid attenuates arsenic induced neuro-inflammation and mitochondrial dysfunction associated apoptosis.
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DOI：
10.1016/j.toxrep.2018.02.017
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发表时间：
2018
影响因子：
--
通讯作者：
Afzal M
中科院分区：
文献类型：
--
作者：
Firdaus F;Zafeer MF;Anis E;Ahmad M;Afzal M
鞣花酸减轻砷介导的大鼠脑组织遗传毒性。鞣花酸改善砷诱导的大鼠脑内ROS和促炎细胞因子水平的恶化。鞣花酸具有调节BAX、Bcl 2和caspase 3的mRNA表达的倾向，提示其神经保护功效。砷作为一种全球性污染物，需要一种潜在的补救措施来对抗其相关的毒性。鞣花酸（EA）是一种已知的具有抗炎、抗氧化和抗凋亡作用的物质，并且它通常存在于水果中。本研究旨在确定EA对砷中毒的保护作用，特别是对Wistar大鼠肾脏炎症和线粒体功能障碍的保护作用。用EA（20和40 mg/kg B.wt; p.o.持续11天）沿着砷（10 mg/kg; p.o. 8天）。采用流式细胞术分析总活性氧水平和线粒体膜电位。还评估了大鼠海马中凋亡和炎症标记物的蛋白质和mRNA表达。我们的研究结果表明，砷暴露增加总ROS的产生和DNA断裂，降低线粒体膜电位，同时增加促凋亡和炎症标志物的表达。表明EA互补剂量依赖性地下调总ROS生成。细胞凋亡标志物BAX和Bcl 2以及炎症标志物IL-1β、TNFα、INFγ在给药后发生了显着改变。此外，它还减弱了对线粒体膜电位的影响。根据我们的研究结果，EA可能证实是一个萌芽的治疗候选人对砷诱导的神经毒性。
Ellagic acid mitigates arsenic mediated genotoxicity in rat brain hippocampi. Ellagic acid ameliorates arsenic induced exacerbation in levels of ROS and pro-inflammatory cytokines in rat brain hippocampi. Ellagic acid has the propensity to modulate mRNA expression of BAX, Bcl2 and caspase3, suggestive of its neuroprotective efficacy. Arsenic, being a global pollutant needs a potential remedy which could fight against its associated toxicities. Ellagic acid (EA) is a known agent for its anti-inflammatory, antioxidant and antiapoptotic effects, and it is commonly found in fruits. The present study is designed to determine protective efficacy of EA against arsenic induced toxicity with special mention to inflammation and mitochondrial dysfunction in hippocampi of wistar rats. Rats were pre-treated with EA (20 and 40 mg/kg b.wt; p.o. for 11 days) along with arsenic (10 mg/kg; p.o. for 8 days). Total reactive oxygen species level and mitochondrial membrane potential were analyzed using flow cytometry. Protein and mRNA expression of apoptotic and inflammatory markers were also evaluated in rat hippocampus. Our results show that arsenic exposure increased total ROS generation and DNA fragmentation, decreased mitochondrial membrane potential alongwith an increase in expression of pro-apoptotic and inflammatory markers. suggesting that EA complementation downregulated total ROS generation dose dependently. Apoptotic markers, BAX and Bcl2 as well as inflammatory markers, IL-1β, TNFα, INFγ got altered significantly on its administration. Moreover, it also attenuated effects on mitochondrial membrane potential. Based on our findings, EA might substantiate to be a budding therapeutic candidate against arsenic induced neurotoxicity.