EFFECTS OF DEHP ON LIVER

邻苯二甲酸二乙基己酯(DEHP)是一种增塑剂，用于 聚乙烯塑料的制造。由于DEHP不是在 塑料，它可能会从塑料容器中迁移出来，污染食物， 水、血液成分，或可直接从塑料摄取。 DEHP是微体脂肪酸omega-羟化的有效诱导剂 和过氧异构体脂肪酸β-氧化系统，但其他 据报道，仓鼠、豚鼠和人类等物种较少。 对DEHP治疗有反应。据报道，DEHP有多种有毒物质 但它对其他物种的影响还没有 学习。DEHP已经成为一个有争议的话题，因为它 作为增塑剂的广泛使用及其可能的毒性影响。政府 监管机构必须决定是否应该限制DEHP的使用。 这一建议将确定羟基化的具体活性 脂肪酸及其邻苯二甲酸单乙基己酯的水解产物 (MEHP)在大鼠、仓鼠、豚鼠和人类微粒体中。结果是 这项研究将决定一种物种专一性是否存在于 邻苯二甲酸酯的代谢。微粒体和过氧化物体的诱导 将在DEHP处理的动物和原代肝细胞中研究酶 用MEHP处理培养1~5天。细胞色素P-450 催化脂肪酸的欧米伽-羟基化，这是由 将对DEHP处理进行分离和鉴定。量化的问题 DEHP诱导的P-450将在肝脏和肝外器官中进行 免疫印迹法检测对照组和DEPH处理组大鼠的DNA含量。微生物体 将接受电泳法和选择性鉴定 通过其抗体介导omega羟化的P-450。抗体 通过与标准曲线的比较，对抗原复合体进行定量。 在灌流的大鼠肝脏中，DEHP的作用也将被研究 检测过氧化氢的解毒作用 释放谷胱甘肽二硫化物。脂质过氧化的堆积 副产物和欧米茄氧化脂肪酸衍生物的加入 转化为磷脂将被测量。这些研究将有助于确定 DEHP对肝细胞的急性生化效应。

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.