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6-羟基-2,2,4-三甲基-1,2,3,4-四氢喹啉减轻实验性帕金森病大鼠的氧化应激和NF-κB介导的炎症反应

6-Hydroxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline Alleviates Oxidative Stress and NF-κB-Mediated Inflammation in Rats with Experimental Parkinson's Disease.

作者信息

Kryl'skii Evgenii D, Razuvaev Grigorii A, Popova Tatyana N, Medvedeva Svetlana M, Shikhaliev Khidmet S

机构信息

Department of Medical Biochemistry, Molecular and Cell Biology, Voronezh State University, Universitetskaya Sq. 1, Voronezh 394018, Russia.

Department of Organic Chemistry, Voronezh State University, Universitetskaya Sq. 1, Voronezh 394018, Russia.

出版信息

Curr Issues Mol Biol. 2023 Sep 21;45(9):7653-7667. doi: 10.3390/cimb45090483.

Abstract

A study was conducted to investigate the effects of different doses of 6-hydroxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (HTHQ) on motor coordination scores, brain tissue morphology, the expression of tyrosine hydroxylase, the severity of oxidative stress parameters, the levels of the p65 subunit of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) factor, and the inflammatory response in rats during the development of rotenone-induced Parkinsonism. The findings indicate that HTHQ, with its antioxidant attributes, reduced the levels of 8-isoprostane, lipid oxidation products, and protein oxidation products. The decrease in oxidative stress due to HTHQ led to a reduction in the mRNA content of proinflammatory cytokines and myeloperoxidase activity, accompanying the drop in the expression of the factor NF-κB. These alterations promoted an improvement in motor coordination scores and increased tyrosine hydroxylase levels, whereas histopathological changes in the brain tissue of the experimental animals were attenuated. HTHQ exhibited greater effectiveness than the comparative drug rasagiline based on the majority of variables.

摘要

开展了一项研究,以调查不同剂量的6-羟基-2,2,4-三甲基-1,2,3,4-四氢喹啉(HTHQ)对鱼藤酮诱导的帕金森病大鼠模型在运动协调评分、脑组织形态、酪氨酸羟化酶表达、氧化应激参数严重程度、活化B细胞核因子κB轻链增强子(NF-κB)因子p65亚基水平以及炎症反应方面的影响。研究结果表明,具有抗氧化特性的HTHQ降低了8-异前列腺素、脂质氧化产物和蛋白质氧化产物的水平。HTHQ引起的氧化应激降低导致促炎细胞因子的mRNA含量和髓过氧化物酶活性降低,同时NF-κB因子的表达下降。这些改变促进了运动协调评分的改善和酪氨酸羟化酶水平的提高,而实验动物脑组织的组织病理学变化则有所减轻。基于大多数变量,HTHQ比对照药物雷沙吉兰表现出更高的有效性。

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