Antiatherogenic Properties of tert-Butylhydroquinone

叔丁基氢醌的抗动脉粥样硬化特性

• 批准号: 6786512
• 负责人: William L Stone
• 金额: $ 10万
• 依托单位: BIOINVENTIONS, LLC
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6786512
• 关键词: acute phase protein; antiatherogenic agent; aorta disorder; atherosclerosis; cardiovascular disorder chemotherapy; cardiovascular disorder risk; cardiovascular pharmacology; cholesterol; computer program /software; dietary lipid; disease /disorder model; drug design /synthesis /production; drug screening /evaluation; genetically modified animals; hydroquinones; laboratory mouse; lipid metabolism; nonhuman therapy evaluation; protein localization; protein metabolism; statistics /biometry; triglycerides

DESCRIPTION (provided by applicant): Atherosclerosis is the underlying cause of most cardiovascular disease and considerable evidence supports the role of hypercholesterolemia as a risk factor for this disease. In preliminary work, we found that tertiary-butyl hydroquinone (TBHQ), at a dose lower than approved for human use, was effective in reducing plasma levels of both total cholesterol and triglycerides in a rat model. TBHQ is phenolic antioxidant commonly used as a food preservative. A patent, "Method for Reducing Blood Cholesterol and/or Blood Triglycerides," was subsequently obtained. The long-term objective of this research proposal is to determine the antiatherogenic potential of TBHQ and advance its commercial development. Our specific aims are to test the efficacy of TBHQ in: (1) reducing aortic atherosclerosis; (2) lowering plasma lipid levels; (3) promoting a less atherogenic lipoprotein profile and; (4) reducing plasma levels of C-reactive protein (CRP). Elevated levels of CRP are a risk factor for cardiovascular disease. In our phase I experiments, we will use the apoE knockout (apoE-/-) mouse model since it has been extensively used to study the antiatherogenic potential of other phenolic antioxidants. Our preliminary market analysis suggests that TBHQ could have a potential market of $100 million per year as a lipid-lowering agent. Commercial development should be accelerated since NIH has already conducted extensive toxicological studies with TBHQ.

描述(申请人提供)：动脉粥样硬化是大多数心血管疾病的根本原因，相当多的证据支持高胆固醇血症是这种疾病的危险因素。在初步工作中，我们发现叔丁基对苯二酚(TBHQ)在低于批准的人类使用剂量时，可以有效地降低大鼠模型中总胆固醇和甘油三酯的水平。TBHQ是一种酚类抗氧化剂，通常用作食品防腐剂。随后获得了专利“降低血液胆固醇和/或甘油三酯的方法”。这项研究计划的长期目标是确定TBHQ的抗动脉粥样硬化潜力，并推动其商业化发展。我们的具体目标是测试TBHQ在以下方面的有效性：(1)减少主动脉粥样硬化；(2)降低血脂水平；(3)促进较少的动脉粥样硬化形成脂蛋白；(4)降低血浆C-反应蛋白(CRP)水平。C反应蛋白水平升高是心血管疾病的危险因素。在我们的第一阶段实验中，我们将使用apoE基因敲除(apoE-/-)小鼠模型，因为它已被广泛用于研究其他酚类抗氧化剂的抗动脉粥样硬化潜力。我们的初步市场分析表明，TBHQ作为一种降脂剂，每年可能有1亿美元的潜在市场。应该加快商业开发，因为NIH已经与TBHQ进行了广泛的毒理学研究。