Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421002, China.
Hunan Provincial Clinical Research Center for Metabolic Associated Fatty Liver Disease, Clinical Research Institute, the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421002, China.
Adv Healthc Mater. 2024 Jan;13(2):e2302466. doi: 10.1002/adhm.202302466. Epub 2023 Nov 7.
Diabetes and its complications, such as diabetes liver disease, is a major problem puzzling people's health. The detection of redox states in its pathological process can effectively help us gain a deeper understanding of the disease. The pair of oxidation-reduction substances peroxynitrite (ONOO ) and glutathione (GSH) is considered to be closely related to their occurrence and development. Thus, direct visualization of ONOO and GSH in diabetes liver disease is critical to evaluate the disease at the molecular level. Herein, two activatable agents NTCF-ONOO and NTCF-GSH are prepared for selectively detecting ONOO and GSH through protection and deprotection strategies based on hydroxyl and amino groups of near-infrared fluorophore. Fluorescence imaging of exogenous and endogenous ONOO and GSH changes in living cells and in vivo is observed. The ONOO and GSH level in the diabetes liver disease cellular model are visualized and the possible redox imbalance mechanism related to the oxidized (NAD ) and reduced (NADH) nicotinamide adenine dinucleotides is explored in this process. Moreover, these probes can sensitively recognize ONOO and GSH in the process of oxidative stress resulting from streptozotocin and streptozotocin/acetaminophen-induced complex diabetic liver disease in vivo. In addition, they can be applied for monitoring the clinical serum sample related with diabetic patients.
糖尿病及其并发症，如糖尿病肝病，是一个令人困扰的健康主要问题。在其病理过程中检测氧化还原状态可以有效地帮助我们更深入地了解这种疾病。过氧亚硝酸盐（ONOO）和谷胱甘肽（GSH）这一对氧化还原物质被认为与它们的发生和发展密切相关。因此，直接可视化糖尿病肝病中的 ONOO 和 GSH 对于在分子水平上评估疾病至关重要。在这里，我们制备了两种可激活的试剂 NTCF-ONOO 和 NTCF-GSH，通过基于近红外荧光团的羟基和氨基的保护和去保护策略，选择性地检测 ONOO 和 GSH。观察了活细胞内和体内外源性和内源性 ONOO 和 GSH 变化的荧光成像。可视化了糖尿病肝病细胞模型中的 ONOO 和 GSH 水平，并探讨了与氧化（NAD）和还原（NADH）烟酰胺腺嘌呤二核苷酸相关的可能氧化还原失衡机制。此外，这些探针可以在链脲佐菌素和乙酰氨基酚诱导的复杂糖尿病肝损伤引起的体内氧化应激过程中，灵敏地识别 ONOO 和 GSH。此外，它们还可以用于监测与糖尿病患者相关的临床血清样本。
