Analytical chemistry 2018, 90, 8108–8115Full text

Han Xiaoyue ,Wang Rui , Song Xinyu,Yu Fabiao* ,Chen Lingxin*

https://pubs.acs.org/doi/abs/10.1021/acs.analchem.8b01306

Abstract

As important active sites of oxidoreductase in mitochondria, selenocysteine (Sec) takes the responsibility for cytoprotective effect and intracellular redox homeostasis. Carbon disulfide (CS₂) is a common solvent in industry, which can inhibit the activities of oxidoreductase and induce oxidative stress. It is necessary to investigate the cytoprotective effect of Sec against CS₂exposure. After integrated, the response moiety 2,4-dinitrobenzenesulfonamide and mitochondrial targeting moiety into the near-infrared heptamethine cyanine fluorophore, we develop a mitochondrial targeting near-infrared ratiometric fluorescent probe Mito-diNO₂ for the selective and sensitive analysis of Sec concentration fluctuations in living cells and in mice models under the stimulation of CS₂. The probe can effectively accumulate in mitochondria and selectively detect the endogenous Sec concentrations in BRL 3A, RH-35, HL-7702, HepG2, and SMMC-7721 cell lines. The results indicate that CS₂ exposure can lead to a decrease of Sec level and result in mitochondrial related acute inflammation. The exogenous supplement of Sec can protect cells from oxidative damage and reduce the symptoms of inflammation. We also establish CS₂ induced acute and chronic hepatitis mice models to examine the tissue toxicity of CS₂ and cytoprotection of Sec in liver. The organism can increase the concentration of Sec to deal with the damage caused by CS₂ in acute hepatitis mice model. Also the exogenous supplement of Sec for the two mice models can effectively defend the CS₂ induced liver damage. The real-time imaging of Sec concentrations in liver can be used to assess the degrees of liver injury during CS₂ poisoning. The above applications make our probe a potential candidate for the clinical accurate diagnosis and treatment of CS₂ poisoning.