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1.
Chem Sci ; 8(5): 4006-4011, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28580117

RESUMO

Drug-induced injury has attracted increasing attention in public health issues. Among them, hepatotoxicity has been regarded as the leading clinical problem caused by drug toxicity. However, owing to the complexity of the involved pathophysiological mechanisms and the lack of noninvasive, straightforward, and real-time tools, drug-induced hepatotoxicity has rarely been predicted satisfactorily. In this paper, by utilizing the reactive species peroxynitrite (ONOO-) as a biomarker, we present a two-photon fluorescent probe, TP-KA, holding rapid response, high specificity and sensitivity towards ONOO-, to investigate drug (acetaminophen and tolcapone)-related liver injury and the remediate effect of N-acetyl cysteine (NAC). With the support of TP-KA, we obtained direct and visual evidence of the upregulation of ONOO- during drug challenge both in live cells and mice, which was accompanied by liver tissue injury and tyrosine nitration. These findings demonstrate that ONOO- is a good and appropriate biomarker of hepatotoxicity, and nitrosative stress may be necessary for acetaminophen and tolcapone to exert their toxicity. Moreover, TP-KA can be employed as a powerful tool to pre-detect drug-induced organism injury and study the effect of antidotes.

2.
Anal Chem ; 88(16): 8019-25, 2016 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-27442152

RESUMO

Hydrogen peroxide, an important biomolecule, receives earnest attention because of its physiological and pathological functions. In this Article, we present the rational design, characterization, and biological application of a mitochondria-targetable NIR fluorescent sensor, Mito-NIRHP, for hydrogen peroxide visualization. Mito-NIRHP utilizes a unique reaction switch, α-ketoamide moiety, to turn on a highly specific, sensitive, and rapid fluorescence response toward hydrogen peroxide coupled with the intramolecular charge transfer strategy. Mito-NIRHP is competent to track endogenously produced hydrogen peroxide in both living cells and living animals. In addition, utilizing Mito-NIRHP, overgeneration of hydrogen peroxide during ischemia-reperfusion injury was directly visualized at both cell and organ levels.


Assuntos
Amidas/química , Corantes Fluorescentes/química , Peróxido de Hidrogênio/análise , Traumatismo por Reperfusão/diagnóstico por imagem , Amidas/síntese química , Animais , Modelos Animais de Doenças , Corantes Fluorescentes/síntese química , Células Hep G2 , Humanos , Raios Infravermelhos , Camundongos , Camundongos Endogâmicos , Estrutura Molecular , Imagem Óptica
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