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Ecotoxicol Environ Saf ; 223: 112597, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34365213


Quercetin is reported to be beneficial to or pose hazards to the health of animals, the inconsistence remains to be recognized and debated. This work was conducted to understand the neuroprotective or neurotoxic properties of quercetin, and investigate the different action mechanisms between low- and high-level quercetin. Therefore, we evaluated brain oxidative stress and monoamine neurotransmitters in adult zebrafish (Danio rerio) after exposure to 1 and 1000 µg/L quercetin. In addition, the brain transcriptional profiles were analyzed to identify genes and pathways that were differentially regulated in the brains. The results of oxidative stress and neurotransmitters suggest that low-level quercetin might be beneficial to nervous system, while high-level quercetin might exert detrimental effects. Furthermore, transcriptional profiles also suggested different toxic mechanisms occurred between low- and high-level quercetin. At 1 µg/L quercetin, enrichment analysis of differently expressed genes (DEGs) revealed that the fanconi anemia pathway might be an important mechanism in neuroprotective effects. At 1000 µg/L quercetin, the up-regulated DEGs were enriched in many Gene Ontology (GO) terms related to neuronal synapses, indicating potential neuroprotective effects; however, enrichment of up-regulated DEGs in GO terms of response to stimulus and the MAPK signaling pathway was also found, which indicated increases of stress. Notably, at 1000 µg/L quercetin, the down-regulated DEGs were enriched in several GO terms related to the proteostasis and the proteasome pathway, indicating impairment of proteasome functions which was involved in neurodegenerative diseases. Moreover, several hub genes involved in the pathology of neurodegenerative diseases were identified by Protein-protein interaction analysis at 1000 µg/L quercetin. Thus, high-level quercetin might pose potential risk inducing neurodegenerative diseases, which should receive more attention in the future. Additionally, our findings may provide awareness to society and researchers about toxicity possibilities of phytochemicals on wildlife and human.

Fármacos Neuroprotetores , Peixe-Zebra , Animais , Encéfalo , Perfilação da Expressão Gênica , Humanos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Quercetina/farmacologia , Peixe-Zebra/genética
Anal Chem ; 92(1): 699-706, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31789017


Pulmonary fibrosis (PF) is a fatal disease with increasing prevalence. Nonradioactive and noninvasive diagnosis of PF at an early stage can improve the prognosis but represents a daunting challenge. Up-regulation of nitric oxide (NO) is a typical microenvironmental feature of PF. Here, we report a small-molecule probe, PNO1, that can fluorogenically sense this microenvironmental feature for PF diagnosis. We demonstrate that PNO1 fluorescence is 6-fold higher in PF-diseased mice lungs than in normal-control groups. In addition to this in vivo result, PNO1 can also be applied in vitro to detect PF-diseased cells and ex vivo to detect PF-diseased tissues from clinical patients. These results highlight PNO1 as a complement to the traditional immunostaining-based methods for PF detection to facilitate quick screening for anti-PF drug candidates.

Corantes Fluorescentes/química , Fibrose Pulmonar/diagnóstico , Bibliotecas de Moléculas Pequenas/química , Animais , Linhagem Celular , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/síntese química , Injeções Intravenosas , Camundongos , Estrutura Molecular , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Imagem Óptica , Fibrose Pulmonar/metabolismo , Bibliotecas de Moléculas Pequenas/administração & dosagem , Bibliotecas de Moléculas Pequenas/síntese química