TY  - JOUR
AU  - Volarevic, Vladislav
AU  - Paunović, Verica G.
AU  - Marković, Zoran M.
AU  - Marković-Simović, Bojana
AU  - Misirkić-Marjanović, Maja
AU  - Todorović-Marković, Biljana
AU  - Bojic, Sanja
AU  - Vucicevic, Ljubica
AU  - Jovanović, Svetlana P.
AU  - Arsenijević, Nebojša N.
AU  - Holclajtner-Antunović, Ivanka D.
AU  - Milosavljević, Momir
AU  - Dramićanin, Miroslav
AU  - Kravić-Stevović, Tamara K.
AU  - Ćirić, Darko
AU  - Lukić, Miodrag L.
AU  - Trajković, Vladimir S.
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/324
AB  - 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-?, and a decrease in IFN-gamma serum levels. In the spleen of GQD-exposed mice, mRNA expression of IFN-? 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-gamma 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.
T2  - ACS Nano
T1  - Large Graphene Quantum Dots Alleviate Immune-Mediated Liver Damage
VL  - 8
IS  - 12
SP  - 12098
EP  - 12109
DO  - 10.1021/nn502466z
ER  - 

@article{
author = "Volarevic, Vladislav and Paunović, Verica G. and Marković, Zoran M. and Marković-Simović, Bojana and Misirkić-Marjanović, Maja and Todorović-Marković, Biljana and Bojic, Sanja and Vucicevic, Ljubica and Jovanović, Svetlana P. and Arsenijević, Nebojša N. and Holclajtner-Antunović, Ivanka D. and Milosavljević, Momir and Dramićanin, Miroslav and Kravić-Stevović, Tamara K. and Ćirić, Darko and Lukić, Miodrag L. and Trajković, Vladimir S.",
year = "2014",
abstract = "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-?, and a decrease in IFN-gamma serum levels. In the spleen of GQD-exposed mice, mRNA expression of IFN-? 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-gamma 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.",
journal = "ACS Nano",
title = "Large Graphene Quantum Dots Alleviate Immune-Mediated Liver Damage",
volume = "8",
number = "12",
pages = "12098-12109",
doi = "10.1021/nn502466z"
}

Volarevic, V., Paunović, V. G., Marković, Z. M., Marković-Simović, B., Misirkić-Marjanović, M., Todorović-Marković, B., Bojic, S., Vucicevic, L., Jovanović, S. P., Arsenijević, N. N., Holclajtner-Antunović, I. D., Milosavljević, M., Dramićanin, M., Kravić-Stevović, T. K., Ćirić, D., Lukić, M. L.,& Trajković, V. S.. (2014). Large Graphene Quantum Dots Alleviate Immune-Mediated Liver Damage. in ACS Nano, 8(12), 12098-12109.
https://doi.org/10.1021/nn502466z

Volarevic V, Paunović VG, Marković ZM, Marković-Simović B, Misirkić-Marjanović M, Todorović-Marković B, Bojic S, Vucicevic L, Jovanović SP, Arsenijević NN, Holclajtner-Antunović ID, Milosavljević M, Dramićanin M, Kravić-Stevović TK, Ćirić D, Lukić ML, Trajković VS. Large Graphene Quantum Dots Alleviate Immune-Mediated Liver Damage. in ACS Nano. 2014;8(12):12098-12109.
doi:10.1021/nn502466z .

Volarevic, Vladislav, Paunović, Verica G., Marković, Zoran M., Marković-Simović, Bojana, Misirkić-Marjanović, Maja, Todorović-Marković, Biljana, Bojic, Sanja, Vucicevic, Ljubica, Jovanović, Svetlana P., Arsenijević, Nebojša N., Holclajtner-Antunović, Ivanka D., Milosavljević, Momir, Dramićanin, Miroslav, Kravić-Stevović, Tamara K., Ćirić, Darko, Lukić, Miodrag L., Trajković, Vladimir S., "Large Graphene Quantum Dots Alleviate Immune-Mediated Liver Damage" in ACS Nano, 8, no. 12 (2014):12098-12109,
https://doi.org/10.1021/nn502466z . .