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The effect of hydroxytyrosol and its nitroderivatives on catechol-O-methyl transferase activity in rat striatal tissue

机译:羟基酪醇及其氮衍生物对大鼠纹状体组织中儿茶酚-O-甲基转移酶活性的影响

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Hydroxytyrosol is a well-known phenolic compound with antioxidant properties that is found in virgin olive oil. Studies have shown that virgin olive oil has neuroprotective effects in rats; thus the purpose of the present study was to investigate the neuroprotective effect of hydroxytyrosol in rats. Additionally, this study aimed to investigate the neuroprotective potential of a homologous series of compounds with better lipophilic profiles in order to increase the assortment of compounds with a putative effect against Parkinson's disease (PD). In this context, the inhibition of catechol-O-methyl transferase (COMT) activity by hydroxytyrosol, nitrohydroxytyrosol, nitrohydroxytyrosol acetate and ethyl nitrohydroxytyrosol ether was investigated by measuring intracellular dopamine and its metabolite levels in the corpus striatum by high performance liquid chromatography (HPLC) with electrochemical detection. The animals received an acute (single dose; 20 mg kg(-1); i.p.) or chronic (one daily dose for 5 days; 20 mg kg(-1); i.p.) treatment of hydroxytyrosol and its nitroderivatives. For comparison, a commercial COMT inhibitor, Ro 41-0960, was also included. Our data show that acute and chronic systemic administration of these compounds produced a clear and statistically significant increase in the intracellular levels of dopamine and its metabolite, 3,4-dihydroxyphenylacetic acid. The increase in dopamine levels was very similar to the increase seen with Ro 41-0960 treatment. The effect of chronic treatment was stronger than that of acute treatment. With respect to the intracellular level of homovanillic acid, Ro 41-0960 produced a statistically significant decrease which it was not observed when hydroxytyrosol and its nitroderivatives were systemically administered. However, the chronic homovanillic acid treatment effect was stronger than the acute treatment. The results suggest that these compounds could inhibit COMT activity.
机译:羟基酪醇是在原始橄榄油中发现的具有抗氧化性能的著名酚类化合物。研究表明,初榨橄榄油对大鼠具有神经保护作用。因此,本研究的目的是研究羟基酪醇对大鼠的神经保护作用。此外,本研究旨在研究具有更好亲脂性的同源系列化合物的神经保护潜力,以增加对帕金森氏病(PD)有假定作用的化合物的种类。在这种情况下,通过高效液相色谱(HPLC)测量细胞内多巴胺及其在纹状体中的代谢水平,研究了羟基酪醇,硝基羟基酪醇,醋酸硝基羟基酪醇和乙基硝基羟基酪醇醚对儿茶酚-O-甲基转移酶(COMT)活性的抑制作用。电化学检测。这些动物接受了羟基酪醇及其硝基衍生物的急性治疗(单次剂量; 20 mg kg(-1);腹膜内)或慢性治疗(每天一次,持续5天; 20 mg kg(-1); i.p。)。为了比较,还包括商品COMT抑制剂Ro 41-0960。我们的数据表明,这些化合物的急性和慢性全身给药在细胞内多巴胺及其代谢物3,4-二羟基苯基乙酸的含量上产生了明显且统计学上显着的增加。多巴胺水平的增加与Ro 41-0960治疗所见的增加非常相似。慢性治疗的效果强于急性治疗。关于高香草酸的细胞内水平,Ro 41-0960产生了统计学上的显着降低,这是当全身施用羟基酪醇及其硝基衍生物时未观察到的。但是,慢性高香草酸的治疗效果比急性治疗强。结果表明这些化合物可以抑制COMT活性。

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