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Title: Large graphene quantum dots alleviate immune-mediated liver damage
Authors: Volarevic, Vladislav
Paunovic, Verica
Markovic, Zoran
Simovic Markovic, Bojana
Misirkic Marjanovic, Maja
Todorović Marković, Biljana
Bojic, Sanja
Vucicevic, Ljubica
J, Svetlana
Arsenijevic, Nebojsa
Holclajtner-Antunović J.
Milosavljevic, Milos
Dramicanin, Miroslav
Kravic-Stevovic, Tamara
Ćirić, Darko
Lukic, Miodrag
Trajkovic, Vladimir
Journal: ACS Nano
Issue Date: 1-Jan-2014
Abstract: © 2014 American Chemical Society. We investigated the effect of large (40 nm) graphene quantum dots (GQDs) in concanavalin A (Con A; 12 mg/kg i.v.)-induced mouse hepatitis, a T cell-mediated liver injury resembling fulminant hepatitis in humans. Intravenously injected GQDs (50 mg/kg) accumulated in liver and reduced Con A-mediated liver damage, as demonstrated by histopathological analysis and a decrease in liver lipid peroxidation and serum levels of liver transaminases. The cleavage of apoptotic markers caspase-3/PARP and mRNA levels of proapoptotic mediators Puma, Noxa, Bax, Bak1, Bim, Apaf1, and p21, as well as LC3-I conversion to autophagosome-Associated LC3-II and expression of autophagy-related (Atg) genes Atg4b, Atg7, Atg12, and beclin-1, were attenuated by GQDs, indicating a decrease in both apoptosis and autophagy in the liver tissue. This was associated with the reduced liver infiltration of immune cells, particularly the T cells producing proinflammatory cytokine IFN-γ, and a decrease in IFN-γ serum levels. In the spleen of GQD-exposed mice, mRNA expression of IFN-γ and its transcription factor T-bet was reduced, while that of the IL-33 ligand ST2 was increased. The hepatoprotective effect of GQDs was less pronounced in ST2-deficient mice, indicating that it might depend on ST2 upregulation. In vitro, GQDs inhibited splenocyte IFN-γ production, reduced the activation of extracellular signal-regulated kinase in macrophage and T cell lines, inhibited macrophage production of the free radical nitric oxide, and reduced its cytotoxicity toward hepatocyte cell line HepG2. Therefore, GQDs alleviate immune-mediated fulminant hepatitis by interfering with T cell and macrophage activation and possibly by exerting a direct hepatoprotective effect.
Type: Article
DOI: 10.1021/nn502466z
ISSN: 19360851
SCOPUS: 84919725926
Appears in Collections:Faculty of Medical Sciences, Kragujevac
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