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A Highly Sensitive Fluorogenic Assay for the Detection of Nephrotoxin-Induced Oxidative Stress in Live Cells and Renal Tissue
bioRxiv - Biochemistry Pub Date : 2020-06-01 , DOI: 10.1101/2020.06.01.121707
Kamalika Mukherjee , Tak Ian Chio , Han Gu , Dan L. Sackett , Susan L. Bane , Sanja Sever

A common manifestation of drug toxicity is kidney injury or nephrotoxicity. Nephrotoxicity frequently leads to termination of clinical trials and drug withdrawals, which jeopardize biomedical progress. Efficient preclinical screening platforms capable of detecting mild signs of kidney damage, which may elicit considerable toxic response in vivo, are essential. A common manifestation of chemical toxicity is oxidative modification of cellular biomolecules. Therefore, we have developed a facile biomolecule carbonyl detection assay that well surpasses the sensitivity of the standard assays in identifying modest forms of renal injury. Using a novel fluorogenic sensor, TFCH, we have demonstrated the applicability of the assay in live kidney cells and in renal tissue. This robust assay can help inform preclinical decisions to recall unsafe drug candidates. Application of this assay in identifying and analyzing diverse pathologies is envisioned.

中文翻译:

用于检测肾毒素诱导的活细胞和肾组织中氧化应激的高灵敏荧光检测法

药物毒性的常见表现是肾损伤或肾毒性。肾毒性经常导致临床试验终止和药物停药,从而危害生物医学进展。有效的临床前筛查平台必须能够检测到轻度的肾脏损害迹象,这可能在体内引起相当大的毒性反应。化学毒性的常见表现是细胞生物分子的氧化修饰。因此,我们已经开发出一种简便的生物分子羰基检测方法,该方法在鉴定适度形式的肾脏损伤方面远远超过了标准方法的敏感性。使用新型荧光传感器TFCH,我们已经证明了该测定法在活肾细胞和肾组织中的适用性。这种强大的测定方法可以帮助您做出临床前决定,以召回不安全的候选药物。设想了该测定法在鉴定和分析各种病理学中的应用。
更新日期:2020-06-01
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