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Malaysian macroalga Padina australis Hauck attenuates high dose corticosterone-mediated oxidative damage in PC12 cells mimicking the effects of depression

机译:马来西亚巨藻Paduck australis Hauck减弱了模拟抑郁症作用的PC12细胞中大剂量皮质酮介导的氧化损伤

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摘要

Oxidative damage has been associated with the pathophysiology of depression. Macroalgae are equipped with antioxidant defense system to counteract the effects of free radicals We explored the use of Malaysian to attenuate high dose corticosterone-mediated oxidative damage in a cellular model mimicking depression. Fresh specimen of was freeze-dried and extracted sequentially with hexanes, ethyl acetate and ethanol. The extracts were screened for their phytochemical contents and antioxidant activities. Ethanol extract demonstrated the most potent antioxidant capacity and was selected for subsequent assays against high dose corticosterone of 600 µM-mediated oxidative damage in the rat pheochromocytoma (PC12) cells. The corticosterone reduced the cell viability, glutathione (GSH) level, aconitase activity, and mitochondrial membrane potential (MMP); and increased the lactate dehydrogenase (LDH) release, intracellular reactive oxygen species (ROS) level and apoptosis. However, the extent of oxidative damage was reversed by 0.25–0.5 mg/mL ethanol extract suggesting a possible role of -based antioxidants in the mitochondrial defense against constant ROS generation and regulation of antioxidant pathway. The effects were similar to that of desipramine, a tricyclic antidepressant. Our findings indicate that can be developed as a mitochondria-targeted antioxidant to mitigate antidepressant-like effects.
机译:氧化损伤与抑郁症的病理生理有关。大型藻类配备了抗氧化剂防御系统,以抵消自由基的影响。我们探索了在模拟抑郁症的细胞模型中使用马来西亚人来减弱大剂量皮质酮介导的氧化损伤。将新鲜的样品冷冻干燥,并依次用己烷,乙酸乙酯和乙醇萃取。筛选提取物的植物化学成分和抗氧化活性。乙醇提取物具有最强的抗氧化能力,因此被选择用于针对大鼠嗜铬细胞瘤(PC12)细胞中600 µM介导的高剂量皮质酮的氧化损伤的后续测定。皮质酮降低细胞活力,谷胱甘肽(GSH)水平,乌头酸酶活性和线粒体膜电位(MMP);并增加了乳酸脱氢酶(LDH)的释放,细胞内活性氧(ROS)的水平和细胞凋亡。然而,0.25-0.5 mg / mL乙醇提取物可逆转氧化损伤的程度,表明基于抗氧化剂的物质可能在线粒体防御恒定ROS生成和抗氧化剂途径调节中发挥作用。其作用与三环类抗抑郁药地昔帕明相似。我们的发现表明,可以将其开发为针对线粒体的抗氧化剂,以减轻类抗抑郁药的作用。

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