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γ-谷维素在减少由鱼藤酮诱导的帕金森病果蝇模型中的神经运动缺陷、多巴胺耗竭和氧化应激方面的有效性。

Effectiveness of γ-oryzanol in reducing neuromotor deficits, dopamine depletion and oxidative stress in a Drosophila melanogaster model of Parkinson's disease induced by rotenone.

作者信息

Araujo Stífani Machado, de Paula Mariane Trindade, Poetini Marcia Rósula, Meichtry Luana, Bortolotto Vandreza Cardoso, Zarzecki Micheli Stefani, Jesse Cristiano Ricardo, Prigol Marina

机构信息

Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, Itaqui CEP 97650-000, RS, Brazil.

Department of Nutrition, UNIPAMPA, Campus Itaqui, RS, Brazil.

出版信息

Neurotoxicology. 2015 Dec;51:96-105. doi: 10.1016/j.neuro.2015.09.003. Epub 2015 Sep 11.

DOI:10.1016/j.neuro.2015.09.003
PMID:26366809
Abstract

The γ-orizanol present in rice bran oil contains a mix of steryl triterpenyl esters of ferulic acid, which is believed to be linked to its antioxidant potential. In this study we investigated the neuroprotective actions of γ-orizanol (ORY) against the toxicity induced by rotenone (ROT) in Drosophila melanogaster. The flies (both genders) aged between 1 and 5 days old were divided into four groups of 50 flies each: (1) control, (2) ORY 25 μM, (3) ROT 500 μM, (4) ORY 25 μM+ROT 500 μM. Flies were concomitantly exposed to a diet containing ROT and ORY for 7 days according to their respective groups. Survival and behavior analyses were carried out in vivo, and ex vivo analyses involved acetylcholinesterase activity (AChE), determination of dopaminergic levels, cellular viability and mitochondrial viability, activities of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), reactive species levels (RS), lipid peroxidation (TBARS) and contents of total thiols and non-proteic thiols (NPSH). Our results show for the first time that ORY not only acts as an endogenous activator of the cellular antioxidant defenses, but it also ameliorates rotenone induced mortality, oxidative stress and mitochondrial dysfunction. Our salient findings regarded the restoration of cholinergic deficits, dopamine levels and improved motor function provided by ORY. These results demonstrate the neuroprotective potential of ORY and that this effect can be potentially due to its antioxidant action. In conclusion, the present results show that ORY is effective in reducing the ROT induced toxicity in D. melanogaster, which showed a neuroprotective action, possibly due to the presence of the antioxidant constituents such as the ferulic acid.

摘要

米糠油中含有的γ-谷维素是阿魏酸的甾醇三萜酯混合物,据信这与其抗氧化潜力有关。在本研究中,我们研究了γ-谷维素(ORY)对黑腹果蝇中鱼藤酮(ROT)诱导的毒性的神经保护作用。将1至5日龄的果蝇(雌雄皆有)分为四组,每组50只:(1)对照组,(2)25μM ORY组,(3)500μM ROT组,(4)25μM ORY + 500μM ROT组。根据各自分组,果蝇连续7天同时接触含有ROT和ORY的食物。在体内进行存活和行为分析,体外分析包括乙酰胆碱酯酶活性(AChE)、多巴胺能水平测定、细胞活力和线粒体活力、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽-S-转移酶(GST)活性、活性物种水平(RS)、脂质过氧化(TBARS)以及总硫醇和非蛋白质硫醇(NPSH)含量。我们的结果首次表明,ORY不仅作为细胞抗氧化防御的内源性激活剂,还能改善鱼藤酮诱导的死亡率、氧化应激和线粒体功能障碍。我们的显著发现涉及ORY对胆碱能缺陷的恢复、多巴胺水平的改善以及运动功能的提升。这些结果证明了ORY的神经保护潜力,并且这种作用可能归因于其抗氧化作用。总之,目前的结果表明ORY能有效降低ROT对黑腹果蝇的诱导毒性,显示出神经保护作用,这可能归因于抗氧化成分如阿魏酸的存在。

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