Mechanisms Of Drug-induced Toxicities

药物引起的毒性机制

• 批准号: 7594368
• 负责人: Lance R Pohl
• 金额: $ 206.43万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 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/7594368
• 关键词: Acetaminophen; Acute Liver Failure; Animal Model; Annual Reports; Antidiabetic Drugs; Antihypertensive Agents; Biological; Blood; Cells; Cholestasis; Chronic Hepatitis; Cirrhosis; Class; Condition; Corticosterone; Dose; Face; Flow Cytometry; Genetic Polymorphism; Genome; Glucocorticoid Receptor; Granuloma; Hepatic; Hepatoprotective Agent; Herbal Medicine; Immunoblastic Lymphadenopathy; Industry; Inhalation Anesthetics; Injury; Interleukin 4 Receptor; Interleukin-10; Interleukin-13; Interleukin-4; Interleukin-6; Interleukins; Knowledge; Lesion; Life; Link; Lipids; Liver; Liver Regeneration; Liver diseases; MAPK9 gene; Marketing; Mediating; Migration Inhibitory Factor; Mitogen-Activated Protein Kinases; Monitor; Mus; Nature; Non-Steroidal Anti-Inflammatory Agents; Pharmaceutical Preparations; Play; Predisposition; Protein Overexpression; Psychotropic Drugs; Public Health; Reaction; Research; Risk; Role; Serum; Severities; Stress; T-Lymphocyte; Testing; Toxic effect; Wild Type Mouse; antimicrobial drug; base; cyclooxygenase 2; cytokine; drug induced liver disease; drug mechanism; mRNA Expression; monocyte; neutrophil; osteopontin; phenylpyruvate tautomerase; post-market; prospective

ANNUAL REPORT FOR 2007 1. This year flow cytometry revealed that the hepatoprotective effects of interleukin (IL)-4 in AILI appeared to be due in part to the regulatory actions of this cytokine on infiltrating neutrophils and monocytes that express IL-4 receptors. 2. This year genome-wide mRNA expression analysis led to the discovery of numerous cellular factors that may play a role in the hepatoprotective effects of IL-13 in AILI. 3. This year we discovered that NK(T) cells played a role in AILI in IL-13 deficient mice, but not in wild type mice suggesting that IL-13 regulates these cells. 4. This year we discovered that endogenous corticosterone released into the blood as a result of hepatocellular injury enhanced the severity of AILI through a mechanism(s) that is mediated by its glucocorticoid receptor. 5. This year we found that stress-induced activation of the mitogen-activated protein kinase, JNK2, protected mice from AILI in part by promoting liver regeneration.

2007年年度报告 1. 今年的流式细胞术显示，白细胞介素 (IL)-4 在 AILI 中的保肝作用似乎部分归因于该细胞因子对表达 IL-4 受体的浸润性中性粒细胞和单核细胞的调节作用。 2. 今年全基因组 mRNA 表达分析发现了许多细胞因子，这些因子可能在 IL-13 对 AILI 的保肝作用中发挥作用。 3. 今年，我们发现 NK(T) 细胞在 IL-13 缺陷小鼠的 AILI 中发挥作用，但在野生型小鼠中则不然，表明 IL-13 调节这些细胞。 4. 今年，我们发现，由于肝细胞损伤，内源性皮质酮释放到血液中，通过其糖皮质激素受体介导的机制增强了 AILI 的严重程度。 5. 今年，我们发现应激诱导的丝裂原激活蛋白激酶 JNK2 的激活部分通过促进肝脏再生来保护小鼠免受 AILI。