EFFECTS OF DEHP ON LIVER

邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种增塑剂， 聚乙烯塑料的制造。 由于DEHP在 塑料，它可能会从塑料容器中迁移并污染食物， 水、血液成分，或者可以直接从塑料中摄入。 DEHP是微粒体脂肪酸ω-羟基化的强效诱导剂 和过氧化物酶体脂肪酸β-氧化系统的比率，但其他 据报道，仓鼠、豚鼠和人类等物种的死亡率较低， 对DEHP治疗有反应。 据报道，DEHP具有多种毒性， 影响率，但其对其他物种的影响还没有得到 研究了 DEHP已经成为一个有争议的话题，因为它 广泛用作增塑剂及其可能的毒性作用。 政府 监管机构必须决定是否应限制DEHP的使用。 该建议将确定羟基化的比活性， 脂肪酸和DEHP的水解产物，邻苯二甲酸单乙基己酯 在大鼠、仓鼠、豚鼠和人微粒体中的MEHP。 结果 这项研究的结果将确定是否存在物种特异性， 邻苯二甲酸盐的代谢。 微粒体和过氧化物酶体的诱导 将在DEHP处理的动物和原代肝细胞中研究酶 用MEHP处理培养物1至5天。 细胞色素P-450 催化脂肪酸的ω-羟基化， DEHP治疗将被隔离和表征。 的定量 DEHP诱导的P-450将在肝脏和肝外器官中进行 通过蛋白质印迹分析对照和DEHP处理的大鼠。 微粒体 将进行电泳和选择性鉴定， 通过其抗体介导ω-羟基化的P-450。 述抗体 并通过与标准曲线比较来定量抗原复合物。 DEHP的影响也将在灌注的大鼠肝脏中进行研究， 检查过氧化氢的解毒作用， 谷胱甘肽二硫化物的释放。 脂质过氧化积累 副产物和ω-氧化脂肪酸衍生物的掺入 将被测量为磷脂。 这些研究将有助于描述 DEHP对肝细胞的急性生化影响。

Di-(2-ethylhexyl)phthalate (DEHP) is a plasticizer that is used in the manufacture of polyvinyl plastics. Since DEHP is not polymerized in the plastic, it may migrate from plastic containers and contaminate food, water, blood components, or may be ingested directly from the plastic. DEHP is a potent inducer of the microsomal fatty acid omega-hydroxylation and peroxisomal fatty acid beta-oxidation systems in rates, but other species such as hamsters, guinea pigs, and humans are reported to be less responsive to DEHP treatment. DEHP is reported to have a variety of toxic effects in the rate, but its effects on other species have not been studied. DEHP has become a controversial subject, because of its widespread use as a plasticizer and its possible toxic effects. Government regulatory bodies must decide if DEHP usage should be restricted. This proposal will determine the specific activities of hydroxylation of fatty acids and the hydrolysis product of DEHP, mono-ethylhexyl phthalate (MEHP) in rats, hamsters, guinea pigs, and human microsomes. The results of this study will determine if a species specificity exists in the metabolism of phthalates. The induction of microsomal and peroxisomal enzymes will be studied in DEHP-treated animals and in primary hepatocyte cultures treated with MEHP for 1 to 5 days. The cytochrome P-450 that catalyzes the omega-hydroxylation of fatty acids that is induced by DEHP-treatment will be isolated and characterized. Quantitation of the P-450 induced by DEHP will be performed in livers and extrahepatic organs of control and DEPH-treated rats by Western blot analysis. The microsomes will be subjected to electrophoresis and the selective identification of the P-450 that mediates omega-hydroxylation by its antibody. The antibody and antigen complex will be quantitated by comparison with standard curves. The effects of DEHP also will be studied in perfused rat livers by examining the detoxification of hydrogen peroxide as measured by the release of glutathione disulfide. the accumulation of lipid peroxidation by-products and the incorporation of omega-oxidized fatty acid derivatives into phospholipids will be measured. These studies will help characterize the acute biochemical effects of DEHP on liver cells.