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Biopharmacological study on the mechanism and the prevention of liver injury caused by organochlorine compounds which pollute the environment

环境有机氯化合物致肝损伤机制及防治的生物药理学研究

基本信息

批准号：
10672114
负责人：
FUKUI Tetsuya
金额：
$ 1.6万
依托单位：
Hoshi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10672114/
关键词：
placenta extract antioxidant oxidative stress liver injury trichloroethylene

项目摘要

Human placenta extract (PLx) possesses various physiologically important activities, such as antioxidant activity and anti-inflammatory activity. Therefore, purification and identification of the active antioxidants of PLx was attempted. Purification was performed successively by 40% methanol precipitation, Sephadex G-50 gel chromatography, and highperformance liquid chromatography (HPLC), and based on HPLC retention times, UV, NMR, and FAD-MS, the isolated components from PLX were identified as uracil, tyrosine, and phenylalanine. In order to confirm whether these compounds have similar function as PLx, effects of the administration of these compounds on the ethanol-induced liver injury of mice were examined. As a result, PLx suppressed ethanol-induced decrease in hepatic glutathione level, increase in thiobarbituric acid reaction substance (TBARS), increase in the activities of glutamate pyruvate transaminase, glutamate oxaloacetate transaminase, and superoxide dismutase, and decreas … More e in the activity of catalase. A mixture of uracil, tyrosine, and phenylalanine showed similar antioxidant activity to PLx, except for failure to suppress the increase in TBARS.Although these results suggest that PLx has some other unknown components to alleviate acute alcoholic liver injury, the mixture of uracil, tyrosine, and phenylalanine appeared to have almost the same ability to suppress acute ethanol-induced liver injury in mice as that of PLx.Next, in vivo antioxidative effects of curcumin were investigated using a trichloroethylene (TCE)-induced oxidative stress model in mouse liver. Increases in the contents of peroxisome and TBARS and decreases in GSH content of mouse liver by the TCE administration were suppressed by the pre-administration of curcumin. TCE-induced changes in the activities of antioxidative enzyme, such as Cu/Zn-SOD, catalase, glutathione reductase, glutathione peroxidase (GPX) and glucose-6-phosphate dehydrogenase (G6PD), were also diminished by curcumin. These results indicate that curcumin significantly suppresses TCE-induced oxidative stress by scavenging various free radicals, and its antioxidative activity seems to be derived from its suppressive effects on the increase in peroxisome content and decrease in GPx and G6PD activities. Less

人胎盘提取物具有多种生理活性，如抗氧化活性和抗炎活性。因此，PLx的活性抗氧化剂的纯化和鉴定进行了尝试。采用40%甲醇沉淀、Sephadex G-50凝胶层析、高效液相色谱（HPLC）等方法对PLX进行纯化，并通过HPLC保留时间、UV、NMR和FAD-MS等方法对分离的组分进行了鉴定。为了确认这些化合物是否具有与PLx类似的功能，检查了这些化合物的给药对乙醇诱导的小鼠肝损伤的影响。结果，PLx抑制了乙醇诱导的肝脏谷胱甘肽水平降低，硫代巴比妥酸反应物质（TBARS）增加，谷氨酸丙酮酸转氨酶、谷氨酸草酰乙酸转氨酶和超氧化物歧化酶活性增加，并降低了肝脏谷胱甘肽水平。 ...更多信息过氧化氢酶的活性。尿嘧啶、酪氨酸和苯丙氨酸的混合物显示出与PLx相似的抗氧化活性，除了不能抑制TBARS的增加。尽管这些结果表明PLx具有一些其他未知的组分来减轻急性酒精性肝损伤，但尿嘧啶、酪氨酸和苯丙氨酸的混合物似乎具有与PLx几乎相同的抑制小鼠急性乙醇诱导的肝损伤的能力。采用三氯乙烯（TCE）诱导的小鼠肝脏氧化应激模型研究了姜黄素的体内抗氧化作用。预先给予姜黄素可抑制TCE引起的小鼠肝脏过氧化物酶体和TBARS含量的增加以及GSH含量的降低。姜黄素还可降低TCE诱导的抗氧化酶活性变化，如Cu/Zn-SOD、过氧化氢酶、谷胱甘肽还原酶、谷胱甘肽过氧化物酶（GPX）和葡萄糖-6-磷酸脱氢酶（G6 PD）。这些结果表明，姜黄素显着抑制三氯乙烯诱导的氧化应激，清除各种自由基，其抗氧化活性似乎是来自其抑制过氧化物酶体含量的增加和GPx和G6 PD活性的降低。少