Illumination of Hydroxyl Radical in Kidney Injury and High‐Throughput Screening of Natural Protectants Using a Fluorescent/Photoacoustic Probe

Abstract The hydroxyl radical (•OH) is shown to play a crucial role in the occurrence and progression of acute kidney injury (AKI). Therefore, the development of a robust •OH probe holds great promise for the early diagnosis of AKI, high‐throughput screening (HTS) of natural protectants, and elucida...

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Main Authors: Han Gao, Lei Sun, Jiwei Li, Qilin Zhou, Haijun Xu, Xiao‐Nan Ma, Renshi Li, Bo‐Yang Yu, Jiangwei Tian
Format: Article
Language:English
Published: Wiley 2023-11-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202303926
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author Han Gao
Lei Sun
Jiwei Li
Qilin Zhou
Haijun Xu
Xiao‐Nan Ma
Renshi Li
Bo‐Yang Yu
Jiangwei Tian
author_facet Han Gao
Lei Sun
Jiwei Li
Qilin Zhou
Haijun Xu
Xiao‐Nan Ma
Renshi Li
Bo‐Yang Yu
Jiangwei Tian
author_sort Han Gao
collection DOAJ
description Abstract The hydroxyl radical (•OH) is shown to play a crucial role in the occurrence and progression of acute kidney injury (AKI). Therefore, the development of a robust •OH probe holds great promise for the early diagnosis of AKI, high‐throughput screening (HTS) of natural protectants, and elucidating the molecular mechanism of intervention in AKI. Herein, the design and synthesis of an activatable fluorescent/photoacoustic (PA) probe (CDIA) for sensitive and selective imaging of •OH in AKI is reported. CDIA has near‐infrared fluorescence/PA channels and fast activation kinetics, enabling the detection of the onset of •OH in an AKI model. The positive detection time of 12 h using this probe is superior to the 48‐hour detection time for typical clinical assays, such as blood urea nitrogen and serum creatinine detection. Furthermore, a method is established using CDIA for HTS of natural •OH inhibitors from herbal medicines. Puerarin is screened out by activating the Sirt1/Nrf2/Keap1 signaling pathway to protect renal cells in AKI. Overall, this work provides a versatile and dual‐mode tool for illuminating the •OH‐related pathological process in AKI and screening additional compounds to prevent and treat AKI.
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spelling doaj.art-b5011b492faf4ea3ab446d36298a808e2023-11-24T08:40:29ZengWileyAdvanced Science2198-38442023-11-011033n/an/a10.1002/advs.202303926Illumination of Hydroxyl Radical in Kidney Injury and High‐Throughput Screening of Natural Protectants Using a Fluorescent/Photoacoustic ProbeHan Gao0Lei Sun1Jiwei Li2Qilin Zhou3Haijun Xu4Xiao‐Nan Ma5Renshi Li6Bo‐Yang Yu7Jiangwei Tian8State Key Laboratory of Natural Medicines Jiangsu Key Laboratory of TCM Evaluation and Translational Research Cellular and Molecular Biology Center School of Traditional Chinese Pharmacy China Pharmaceutical University Nanjing 211198 P. R. ChinaJiangsu Co‐innovation Center of Efficient Processing and Utilization of Forest Resources, Key Laboratory of Forestry Genetics & Biotechnology of Ministry of Education, Jiangsu Provincial Key Lab for the Chemistry and Utilization of Agroforest Biomass College of Chemical Engineering Nanjing Forestry University Nanjing 210037 P. R. ChinaState Key Laboratory of Natural Medicines Jiangsu Key Laboratory of TCM Evaluation and Translational Research Cellular and Molecular Biology Center School of Traditional Chinese Pharmacy China Pharmaceutical University Nanjing 211198 P. R. ChinaState Key Laboratory of Natural Medicines Jiangsu Key Laboratory of TCM Evaluation and Translational Research Cellular and Molecular Biology Center School of Traditional Chinese Pharmacy China Pharmaceutical University Nanjing 211198 P. R. ChinaJiangsu Co‐innovation Center of Efficient Processing and Utilization of Forest Resources, Key Laboratory of Forestry Genetics & Biotechnology of Ministry of Education, Jiangsu Provincial Key Lab for the Chemistry and Utilization of Agroforest Biomass College of Chemical Engineering Nanjing Forestry University Nanjing 210037 P. R. ChinaState Key Laboratory of Natural Medicines Jiangsu Key Laboratory of TCM Evaluation and Translational Research Cellular and Molecular Biology Center School of Traditional Chinese Pharmacy China Pharmaceutical University Nanjing 211198 P. R. ChinaState Key Laboratory of Natural Medicines Jiangsu Key Laboratory of TCM Evaluation and Translational Research Cellular and Molecular Biology Center School of Traditional Chinese Pharmacy China Pharmaceutical University Nanjing 211198 P. R. ChinaState Key Laboratory of Natural Medicines Jiangsu Key Laboratory of TCM Evaluation and Translational Research Cellular and Molecular Biology Center School of Traditional Chinese Pharmacy China Pharmaceutical University Nanjing 211198 P. R. ChinaState Key Laboratory of Natural Medicines Jiangsu Key Laboratory of TCM Evaluation and Translational Research Cellular and Molecular Biology Center School of Traditional Chinese Pharmacy China Pharmaceutical University Nanjing 211198 P. R. ChinaAbstract The hydroxyl radical (•OH) is shown to play a crucial role in the occurrence and progression of acute kidney injury (AKI). Therefore, the development of a robust •OH probe holds great promise for the early diagnosis of AKI, high‐throughput screening (HTS) of natural protectants, and elucidating the molecular mechanism of intervention in AKI. Herein, the design and synthesis of an activatable fluorescent/photoacoustic (PA) probe (CDIA) for sensitive and selective imaging of •OH in AKI is reported. CDIA has near‐infrared fluorescence/PA channels and fast activation kinetics, enabling the detection of the onset of •OH in an AKI model. The positive detection time of 12 h using this probe is superior to the 48‐hour detection time for typical clinical assays, such as blood urea nitrogen and serum creatinine detection. Furthermore, a method is established using CDIA for HTS of natural •OH inhibitors from herbal medicines. Puerarin is screened out by activating the Sirt1/Nrf2/Keap1 signaling pathway to protect renal cells in AKI. Overall, this work provides a versatile and dual‐mode tool for illuminating the •OH‐related pathological process in AKI and screening additional compounds to prevent and treat AKI.https://doi.org/10.1002/advs.202303926acute kidney injuryhigh‐throughput screeninghydroxyl radicalmolecular probenatural products
spellingShingle Han Gao
Lei Sun
Jiwei Li
Qilin Zhou
Haijun Xu
Xiao‐Nan Ma
Renshi Li
Bo‐Yang Yu
Jiangwei Tian
Illumination of Hydroxyl Radical in Kidney Injury and High‐Throughput Screening of Natural Protectants Using a Fluorescent/Photoacoustic Probe
Advanced Science
acute kidney injury
high‐throughput screening
hydroxyl radical
molecular probe
natural products
title Illumination of Hydroxyl Radical in Kidney Injury and High‐Throughput Screening of Natural Protectants Using a Fluorescent/Photoacoustic Probe
title_full Illumination of Hydroxyl Radical in Kidney Injury and High‐Throughput Screening of Natural Protectants Using a Fluorescent/Photoacoustic Probe
title_fullStr Illumination of Hydroxyl Radical in Kidney Injury and High‐Throughput Screening of Natural Protectants Using a Fluorescent/Photoacoustic Probe
title_full_unstemmed Illumination of Hydroxyl Radical in Kidney Injury and High‐Throughput Screening of Natural Protectants Using a Fluorescent/Photoacoustic Probe
title_short Illumination of Hydroxyl Radical in Kidney Injury and High‐Throughput Screening of Natural Protectants Using a Fluorescent/Photoacoustic Probe
title_sort illumination of hydroxyl radical in kidney injury and high throughput screening of natural protectants using a fluorescent photoacoustic probe
topic acute kidney injury
high‐throughput screening
hydroxyl radical
molecular probe
natural products
url https://doi.org/10.1002/advs.202303926
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