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

人胎盘提取物具有多种重要的生理活性，如抗氧化活性和抗炎活性。因此，本文试图对PLx的活性抗氧化剂进行纯化和鉴定。采用40%甲醇沉淀、Sephadex G-50凝胶层析、高效液相色谱（HPLC）等方法进行纯化，通过HPLC保留时间、UV、NMR、FAD-MS等方法鉴定PLX中分离组分为尿嘧啶、酪氨酸和苯丙氨酸。为了证实这些化合物是否具有与PLx相似的功能，我们研究了这些化合物对乙醇性小鼠肝损伤的影响。结果表明，PLx抑制了乙醇诱导的肝脏谷胱甘肽水平下降，硫代巴比妥酸反应物质（TBARS）升高，谷氨酸丙酮转氨酶、谷氨酸草酰乙酸转氨酶和超氧化物歧化酶活性升高，过氧化氢酶活性降低。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。虽然这些结果表明PLx有一些其他未知的成分可以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酒精性肝损伤的能力。接下来，采用三氯乙烯（TCE）诱导的小鼠肝脏氧化应激模型，研究姜黄素的体内抗氧化作用。姜黄素可抑制TCE对小鼠肝脏过氧化物酶体和TBARS含量的升高和GSH含量的降低。姜黄素也降低了tce诱导的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（G6PD）等抗氧化酶活性。这些结果表明，姜黄素通过清除多种自由基显著抑制tce诱导的氧化应激，其抗氧化活性可能来源于抑制过氧化物酶体含量的增加和GPx和G6PD活性的降低。少

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