Nano-Antioxidants as a Therapeutic for Preclinical Models of NAFLD

纳米抗氧化剂作为 NAFLD 临床前模型的治疗方法

基本信息

批准号：
8537451
负责人：
ROBIA G PAUTLER
金额：
$ 22.12万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8537451
关键词：
Address Antioxidants Ascorbic Acid Biochemistry Carbon Cells Cessation of life Choline Cirrhosis Clinical Trials Data Deposition Development Diabetes Mellitus Diet Digestive System Disorders Disease Disease model Dose Effectiveness Enzymes Exhibits Fatty acid glycerol esters Fibrosis Foundations Goals Health Hepatocyte Histopathology Hypertriglyceridemia Image Individual Institutes Insulin Resistance Kidney Diseases Knowledge Leptin Lipids Liver Liver Dysfunction Liver diseases Manuscripts Metabolic syndrome Methionine Methods Mission Modeling Nanostructures Nanotechnology Obesity Outcome Oxidants Oxidative Stress Pathology Physiological Polyethylenes Porifera Portal Hypertension Pre-Clinical Model Preparation Prevalence Primary carcinoma of the liver cells Process Public Health Reactive Oxygen Species Recycling Research Risk Factors Role Structure Superoxide Dismutase Therapeutic Time Vitamin E Work alpha Tocopherol base cell type choline deficient diet chronic liver disease cohort diabetic fast food high risk improved in vivo innovation liver function liver injury mitochondrial dysfunction mouse model nano nanomaterials nanostructured non-alcoholic fatty liver nonalcoholic steatohepatitis novel prevent

项目摘要

DESCRIPTION (provided by applicant): Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver diseases, ranging from simple steatosis (fat in the liver) to non-alcoholic steatohepatitis (NASH) to cirrhosis. According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), it is the most common form of chronic liver disease and with the risk factors of obesity, diabetes, and metabolic syndrome on the rise, the prevalence of NAFLD is also expected to increase. While the role of oxidative stress in NAFLD is accepted, what is not known is the effectiveness of reducing oxidative stress in preclinical models of NAFLD. Without this knowledge, we cannot determine the utility of novel classes of high- potency antioxidants as potential therapeutics for NAFLD damage. To develop antioxidants for NAFLD that exhibit potent antioxidant activity, that do not pass radicals on to other molecules and that can be targeted, we have turned to nanotechnology. These nano-antioxidants, polyethylene glycolated hydrophilic carbon clusters (PEG-HCCs), are based on carbon nano structures that have conjugated ring structures so that they act as terminal oxidant acceptors or radical "sponges". We have also demonstrated that these PEG-HCCs can be targeted to specific cell types (manuscript in preparation). Our long term goal is to understand the mechanisms of reactive oxygen species (ROS) in NAFLD pathology in order to develop effective therapeutics that can prevent and potentially reverse damage due to oxidative stress. Our objective is to determine the effect of reducing ROS through high-efficiency novel antioxidant compounds on the development of NAFLD pathology by in vivo imaging, biochemistry and histopathology in mouse models of NAFLD. Our central hypothesis is that reducing ROS will improve liver function, reduce liver damage and oxidative stress in mouse models of NAFLD. The rationale for the proposed work is that a mechanistic understanding of oxidative stress on NAFLD pathologies will lay the foundation for viable therapeutic approaches.

描述（由申请人提供）：非酒精性脂肪肝病（NAFLD）涵盖了一系列肝病，从简单的脂肪变性（肝脏中的脂肪）到非酒精性脂肪性肝炎（NASH）到cirrhosis。根据美国国家糖尿病和消化和肾脏疾病（NIDDK）的说法，它是慢性肝病的最常见形式，并且肥胖，糖尿病和代谢综合征的危险因素随着兴起而上升，NAFLD的流行也有望增加。尽管接受氧化应激在NAFLD中的作用，但尚不清楚的是减少NAFLD临床前模型中氧化应激的有效性。没有这些知识，我们将无法确定新颖的高效力抗氧化剂类别作为NAFLD损害的潜在治疗剂。为了开发出具有有效抗氧化活性的NAFLD的抗氧化剂，这些活性不会将自由基传递到其他分子，并且可以靶向，我们已转向纳米技术。这些纳米抗氧化剂，聚乙烯糖溶质的亲水碳液（PEG-HCC）是基于具有共轭环结构的碳纳米结构，使它们充当末端氧化剂受体或自由基“ spongens”。我们还证明，这些PEG-HCC可以针对特定的细胞类型（制备中的手稿）。我们的长期目标是了解NAFLD病理中活性氧（ROS）的机制，以开发有效的治疗剂，这些治疗剂可以预防并可能由于氧化应激而导致的损害。我们的目标是通过高效新颖的抗氧化剂化合物来确定ROS对NAFLD小鼠模型中体内成像，生物化学和组织病理学的NAFLD病理学发展的影响。我们的中心假设是，减少ROS将改善肝功能，减少NAFLD小鼠模型中的肝损伤和氧化应激。拟议工作的理由是，对NAFLD病理学的氧化应激的机械理解将为可行的治疗方法奠定基础。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Hydrophilic carbon clusters as therapeutic, high-capacity antioxidants.

DOI：
10.1016/j.tibtech.2014.08.005
发表时间：
2014-10
期刊：
TRENDS IN BIOTECHNOLOGY
影响因子：
17.3
作者：
Samuel, Errol L. G.;Duong, MyLinh T.;Bitner, Brittany R.;Marcano, Daniela C.;Tour, James M.;Kent, Thomas A.
通讯作者：
Kent, Thomas A.

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