MECHANISM OF DI(2-ETHYLHEXYL)PHTHALATE HEPATOTOXICITY

邻苯二甲酸二(2-乙基己基)酯的肝毒性机制

• 批准号: 4693194
• 负责人: R L MELNICK
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4693194
• 关键词: acetyl coA; catalase; chemical carcinogenesis; diethylhexylphthalate; free radicals; glutathione peroxidase; hepatotoxin; hydrogen peroxide; lipid peroxides; liver neoplasms; peroxidation; peroxisome; superoxide dismutase; superoxides; toxicant interaction

In a rodent bioassay conducted by the National Toxicology Program, di(2-ethyl-hexyl)phthalate (DEHP) was found to be carcinogenic for the liver in B6C3F1 mice and F344 rats. Since DEHP also causes peroxisome proliferation, it has been suggested that the carcinogenicity of this chemical may be related to excessive peroxisomal production of H2O2. It is the objective of this project to examine the changes in H2O2 concentrations resulting from peroxisomal fatty acyl-CoA oxidation and catalase activity in livers of rats and mice treated with DEHP. Further assessment of an involvement of reactive intermediates of oxygen reduction in DEHP induced hepatotoxicity will be made from measurements of (a) activities of enzymes that eliminate toxic oxygen products (catalase, superoxide dismutase, glutathione peroxidase), (b) lipid peroxidation, and (c) superoxide anion radical production.

在国家毒理学计划进行的啮齿动物生物测定中， 邻苯二甲酸二（2-乙基己基）酯（DEHP）被发现是致癌的， B6 C3 F1小鼠和F344大鼠的肝脏。 由于DEHP也会导致过氧化物酶体 增殖，已经表明，这种致癌性 化学物质可能与过氧化氢的过量产生有关。 是 本项目的目的是检查H2 O2浓度的变化 由过氧化物酶体脂肪酰辅酶A氧化和过氧化氢酶活性引起 在用DEHP处理的大鼠和小鼠的肝脏中。 进一步评估 DEHP诱导的氧还原反应中间体的参与 肝毒性将通过测量（a）酶的活性 清除有毒的氧产物（过氧化氢酶，超氧化物歧化酶， 谷胱甘肽过氧化物酶），（B）脂质过氧化，和（c）超氧阴离子 激进的生产。