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）：非酒精性脂肪性肝病（NAFLD）涵盖一系列肝脏疾病，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）再到肝硬化。根据美国国家糖尿病、消化和肾脏疾病研究所 (NIDDK) 的数据，NAFLD 是最常见的慢性肝病，随着肥胖、糖尿病和代谢综合征危险因素的增加，预计 NAFLD 的患病率也会增加增加。虽然氧化应激在 NAFLD 中的作用已被接受，但尚不清楚在 NAFLD 临床前模型中减少氧化应激的有效性。如果没有这些知识，我们就无法确定新型高效抗氧化剂作为 NAFLD 损伤的潜在治疗方法的效用。为了开发具有强大抗氧化活性、不会将自由基传递给其他分子并且可以靶向的 NAFLD 抗氧化剂，我们转向了纳米技术。这些纳米抗氧化剂聚乙二醇化亲水碳簇（PEG-HCC）基于具有共轭环结构的碳纳米结构，因此它们充当末端氧化剂受体或自由基“海绵”。我们还证明这些 PEG-HCC 可以靶向特定的细胞类型（手稿正在准备中）。我们的长期目标是了解 NAFLD 病理学中活性氧 (ROS) 的机制，以便开发有效的治疗方法，预防并可能逆转氧化应激造成的损伤。我们的目标是通过 NAFLD 小鼠模型的体内成像、生物化学和组织病理学，确定通过高效新型抗氧化剂化合物减少 ROS 对 NAFLD 病理学发展的影响。我们的中心假设是，减少 ROS 将改善 NAFLD 小鼠模型的肝功能，减少肝损伤和氧化应激。这项工作的基本原理是，对 NAFLD 病理学氧化应激的机制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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