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Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes.

ABSTRACT: 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.

SUBMITTER: Đurasevic S

PROVIDER: S-EPMC8226855 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes.

Đurašević Siniša S Pejić Snežana S Grigorov Ilijana I Nikolić Gorana G Mitić-Ćulafić Dragana D Dragićević Milan M Đorđević Jelena J Todorović Vukotić Nevena N Đorđević Neda N Todorović Ana A Drakulić Dunja D Veljković Filip F Pajović Snežana B SB Todorović Zoran Z

Antioxidants (Basel, Switzerland) 20210604 6

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 incre ...[more]

PMID: 34199786

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Project description:Introduction: C60 fullerene has received great attention as a candidate for biomedical applications. Due to unique structure and properties, C60 fullerene nanoparticles are supposed to be useful in drug delivery, photodynamic therapy (PDT) of cancer, and reversion of tumor cells' multidrug resistance. The aim of this study was to elucidate the possible molecular mechanisms involved in photoexcited C60 fullerene-dependent enhancement of cisplatin toxicity against leukemic cells resistant to cisplatin. Methods: Stable homogeneous pristine C60 fullerene aqueous colloid solution (10-4 ?, purity 99.5%) was used in the study. The photoactivation of C60 fullerene accumulated by L1210R cells was done by irradiation in microplates with light-emitting diode lamp (420-700 nm light, 100 mW·cm-2). Cells were further incubated with the addition of Cis-Pt to a final concentration of 1 ?g/mL. Activation of p38 MAPK was visualized by Western blot analysis. Flow cytometry was used for the estimation of cells distribution on cell cycle. Mitochondrial membrane potential (??m) was estimated with the use of fluorescent potential-sensitive probe TMRE (Tetramethylrhodamine Ethyl Ester). Results: Cis-Pt applied alone at 1 ?g/mL concentration failed to affect mitochondrial membrane potential in L1210R cells or cell cycle distribution as compared with untreated cells. Activation of ROS-sensitive proapoptotic p38 kinase and enhanced content of cells in subG1 phase were detected after irradiation of L1210R cells treated with 10-5M C60 fullerene. Combined treatment with photoexcited C60 fullerene and Cis-Pt was followed by the dissipation of ??m at early-term period, blockage of cell transition into S phase, and considerable accumulation of cells in proapoptotic subG1 phase at prolonged incubation. Conclusion: The effect of the synergic cytotoxic activity of both agents allowed to suppose that photoexcited C60 fullerene promoted Cis-Pt accumulation in leukemic cells resistant to Cis-Pt. The data obtained could be useful for the development of new approaches to overcome drug-resistance of leukemic cells.

Dataset Information

Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes.

Publications

Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes.

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