Evaluation of Glutathione S-Transferase Inhibition Effects on Idiopathic Pulmonary Fibrosis Therapy with a Near-Infrared Fluorescent Probe in Cell and Mice Models.

Abstract	Idiopathic pulmonary fibrosis (IPF) is a lung-limited and progressive fibrotic disease. The early diagnosis and therapies of IPF are still full of clinical challenges. Glutathione S-transferase (GSTs) plays significant roles in promoting the formation of pulmonary fibrosis. Herein, we report a fluorescent probe (Cy-GST) for the detection of GSTs concentration fluctuations in cells and in mice models. The probe can selectively and sensitively respond to GSTs with an "off-on" type fluorescence switch. Our results demonstrated that the level of intracellular GSTs increase in the pulmonary fibrosis cells and mice models. And the IPF patients hold high levels of GSTs concentrations. Thus, GSTs are likely to play important roles in pulmonary fibrosis. The inhibitor of GSTs TLK117 can reduce the severity of pulmonary fibrosis. The synergistic treatment of TLK117 and pirfenidone have better therapeutic effects than only using pirfenidone in pulmonary fibrosis mice models. The level of GSTs in IPF may be a new potential marker for IPF diagnosis. And the inhibition of GSTs may be a new therapeutic strategy for IPF treatment.
Authors	Na He, Song Bai, Yan Huang, Yanlong Xing, Lingxin Chen, Fabiao Yu, Changjun Lv
Journal	Analytical chemistry (Anal Chem) Vol. 91 Issue 8 Pg. 5424-5432 (04 16 2019) ISSN: 1520-6882 [Electronic] United States
PMID	30869868 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Carbocyanines Enzyme Inhibitors Fluorescent Dyes gamma-Glu-S-BzCys-PhGly diethyl ester Glutathione Transferase Glutathione
Topics	Animals Carbocyanines (chemical synthesis, chemistry) Disease Models, Animal Enzyme Inhibitors (chemical synthesis, chemistry, pharmacology) Fluorescent Dyes (chemical synthesis, chemistry) Glutathione (analogs & derivatives, chemical synthesis, chemistry, pharmacology) Glutathione Transferase (analysis, antagonists & inhibitors, metabolism) Idiopathic Pulmonary Fibrosis (diagnostic imaging, drug therapy, metabolism) Infrared Rays Mice Mice, Inbred C57BL Optical Imaging Particle Size Surface Properties

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