DRUG-INDUCED NEPHROTOXICITY: A CELL CULTURE APPROACH

药物引起的肾毒性：细胞培养方法

• 批准号: 3447341
• 负责人: MARY ANN SENS
• 金额: $ 4.86万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-23 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3447341
• 关键词: aminoglycoside antibiotics; cell bank /registry; cell population study; cytotoxicity; dosage; drug adverse effect; growth media; histopathology; human tissue; image processing; ion transport; kidney function; kidney pharmacology; lysozyme; radiotracer; renal toxin; renal tubule; streptomycin

The long-term objective of the proposed research plan is the formation of an in vitro cell culture model system for the study of aminoglycoside-induced nephrotoxicity. The foundation for this model system rests on a newly established cell culture of the human renal proximal convoluted tubule. Preliminary data has clearly shown that these cells respond to aminoglycoside exposure by formation of lysosomal myeloid bodies. The specific aims of the proposed research is initially to reinforce preliminary findings suggesting that aminoglycoside toxicity and myeloid body formation do not correlate directly. Rather, it appears that the least toxic aminoglycosides are the most efficient at inducing myeloid body formation. Additional specific aims center on an overall assessment of lysosomal function and ion transport alterations elicited by exposure to the aminoglycosides. The above parameters will be further perturbed to enhance and/or correct these alterations by changing the cation composition of the serum-free growth medium in which these cells grow. An understanding of the mechanism of aminoglycoside-induced nephrotoxicity may lead to clinical improvements in hospitalized patients suffering from sepsis.

拟议研究计划的长期目标是形成 一种用于体外细胞培养研究的模型系统 氨基糖苷类药物致肾毒性。这一模式的基础 该系统建立在新建立的人类肾脏细胞培养基础上 近端曲管。初步数据清楚地表明，这些 细胞对氨基糖苷类化合物的反应是通过形成溶酶体髓系来实现的 身体。拟议研究的具体目的最初是 加强了初步研究结果，表明氨基糖苷类毒性和 髓系小体的形成并不直接相关。相反，看起来 毒性最小的氨基糖苷类化合物诱导髓系细胞的效率最高 身体编队。其他具体目标以全面评估为中心 接尘引起的溶酶体功能和离子转运改变 氨基糖苷类。上述参数将进一步扰动到 通过改变阳离子组成来增强和/或纠正这些变化 这些细胞在无血清的生长介质中生长。一个 了解氨基糖苷类药物所致肾毒性的机制可能 导致住院患者的临床改善 败血症。