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Evaluation Selenocysteine Protective Effect in Carbon Disulfide Induced Hepatitis with a Mitochondrial Targeting Ratiometric Near-Infrared Fluorescent Probe
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posted on 2018-06-04, 00:00 authored by Xiaoyue Han, Rui Wang, Xinyu Song, Fabiao Yu, Lingxin ChenAs
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 CS2 exposure. 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.
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Sec concentration fluctuationsRHnear-infrared heptamethine cyanine fluorophoreCS 2 poisoningmice modelsintracellular redox homeostasisHLCS 2 exposurecytoprotective effectMitochondrial Targeting Ratiometric Near-InfraredCarbon Disulfide Induced Hepatitishepatitis mice modelsexogenous supplementhepatitis mice modelBRLSec concentrationsSMMC -7721 cell linesCS 2
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