Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes
Siniša Đurašević,
Snežana Pejić,
Ilijana Grigorov,
Gorana Nikolić,
Dragana Mitić-Ćulafić,
Milan Dragićević,
Jelena Đorđević,
Nevena Todorović Vukotić,
Neda Đorđević,
Ana Todorović,
Dunja Drakulić,
Filip Veljković,
Snežana B. Pajović,
Zoran Todorović
Affiliations
Siniša Đurašević
Faculty of Biology, University of Belgrade, Studentski Trg 16, 11000 Belgrade, Serbia
Snežana Pejić
“Vinča” Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Mike Petrovića Alasa 12–14, 11000 Belgrade, Serbia
Ilijana Grigorov
Institute for Biological Research “Siniša Stanković”, National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia
Gorana Nikolić
Faculty of Medicine, University of Belgrade, Dr. Subotića 8, 11000 Belgrade, Serbia
Dragana Mitić-Ćulafić
Faculty of Biology, University of Belgrade, Studentski Trg 16, 11000 Belgrade, Serbia
Milan Dragićević
Institute for Biological Research “Siniša Stanković”, National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia
Jelena Đorđević
Faculty of Biology, University of Belgrade, Studentski Trg 16, 11000 Belgrade, Serbia
Nevena Todorović Vukotić
“Vinča” Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Mike Petrovića Alasa 12–14, 11000 Belgrade, Serbia
Neda Đorđević
“Vinča” Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Mike Petrovića Alasa 12–14, 11000 Belgrade, Serbia
Ana Todorović
“Vinča” Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Mike Petrovića Alasa 12–14, 11000 Belgrade, Serbia
Dunja Drakulić
“Vinča” Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Mike Petrovića Alasa 12–14, 11000 Belgrade, Serbia
Filip Veljković
“Vinča” Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Mike Petrovića Alasa 12–14, 11000 Belgrade, Serbia
Snežana B. Pajović
“Vinča” Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Mike Petrovića Alasa 12–14, 11000 Belgrade, Serbia
Zoran Todorović
Faculty of Medicine, University of Belgrade, Dr. Subotića 8, 11000 Belgrade, Serbia
Thioacetamide (TAA) is widely used to study liver toxicity accompanied by oxidative stress, inflammation, cell necrosis, fibrosis, cholestasis, and hepatocellular carcinoma. As an efficient free radical’s scavenger, C60 fullerene is considered a potential liver-protective agent in chemically-induced liver injury. In the present work, we examined the hepatoprotective effects of two C60 doses dissolved in virgin olive oil against TAA-induced hepatotoxicity in rats. We showed that TAA-induced increase in liver oxidative stress, judged by the changes in the activities of SOD, CAT, GPx, GR, GST, the content of GSH and 4-HNE, and expression of HO-1, MnSOD, and CuZnSOD, was more effectively ameliorated with a lower C60 dose. Improvement in liver antioxidative status caused by C60 was accompanied by a decrease in liver HMGB1 expression and an increase in nuclear Nrf2/NF-κB p65 ratio, suggesting a reduction in inflammation, necrosis and fibrosis. These results were in accordance with liver histology analysis, liver comet assay, and changes in serum levels of ALT, AST, and AP. The changes observed in gut microbiome support detrimental effects of TAA and hepatoprotective effects of low C60 dose. Less protective effects of a higher C60 dose could be a consequence of its enhanced aggregation and related pro-oxidant role.
