DRUG-INDUCED NEPHROTOXICITY: A CELL CULTURE APPROACH

拟议研究计划的长期目标是形成 用于研究的体外细胞培养模型系统 氨基糖苷类诱导的肾毒性。 这个模型的基础 系统依赖于新建立的人肾细胞培养， 近曲小管 初步数据显示， 细胞通过形成溶酶体髓样对氨基糖苷类药物的暴露作出反应 尸体 拟议研究的具体目标最初是 强化了初步发现，表明氨基糖苷类药物具有毒性， 髓样体形成没有直接关系。 相反， 毒性最小的氨基糖苷类药物在诱导骨髓细胞增殖方面最有效 身体形成 额外的具体目标集中在总体评估上 溶酶体功能和离子转运改变引起的暴露于 氨基糖苷类 上述参数将进一步扰动， 通过改变阳离子组成来增强和/或校正这些改变 这些细胞生长的无血清生长培养基。 一个 了解氨基糖苷类抗生素诱导的肾毒性机制， 导致患有以下疾病的住院患者的临床改善： 败血症

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.