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Published in: Digestive Diseases and Sciences 1/2020

01-01-2020 | Primary Sclerosing Cholangitis | Original Article

Effects of Pristine C60 Fullerenes on Liver and Pancreas in α-Naphthylisothiocyanate-Induced Cholangitis

Authors: Halyna M. Kuznietsova, Natalia V. Dziubenko, Oksana V. Lynchak, Tetyana S. Herheliuk, Dmytro K. Zavalny, Olga V. Remeniak, Yuriy I. Prylutskyy, Uwe Ritter

Published in: Digestive Diseases and Sciences | Issue 1/2020

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Abstract

Background

A significant role in pathogenesis of cholangitis is attributed to excessive reactive oxygen species production and oxidative stress. Therefore, antioxidants could be promising therapeutics.

Aims

The effects of powerful free radical scavenger C60 fullerene on hepatic and pancreatic manifestations of acute and chronic cholangitis in rats were aimed to be discovered.

Methods

Acute (AC, 3 days) and chronic (CC, 28 days) cholangitis models were simulated by single (AC) and 4 weekly (CC) α-naphthylisothiocyanate per os administrations. Pristine C60 fullerene aqueous colloid solution (C60FAS, 0.15 mg/ml, size of aggregates 1.2–100 nm) was administered either per os or intraperitoneally at a dose of 0.5 mg/kg C60 fullerene daily (AC) and every other day (CC). Prednisolone was used as a reference. Liver and pancreas autopsies were analyzed, and blood serum biochemical markers were measured. Pan-cytokeratin expression in HepG2 cells was assessed after 48-h incubation with C60FAS.

Results

On AC, C60FAS normalized elevated bilirubin, alkaline phosphatase, and triglycerides, diminished fibrotic alterations in liver, and improved pancreas state when applied by both ways. Additionally, C60FAS per os significantly reduced the signs of inflammation in liver and pancreas. On CC, C60FAS also mitigated liver fibrosis and inflammation, improved pancreas state, and normalized alkaline phosphatase and triglycerides. The remedy effect of C60FAS was more expressed compared to that of prednisolone on both models. Furthermore, C60FAS inhibited pan-cytokeratin expression in HepG2 cells in a dose-dependent manner.

Conclusion

Pristine C60 fullerene inhibits liver inflammation and fibrogenesis and partially improved liver and pancreas state under acute and chronic cholangitis.
Literature
1.
go back to reference Molodecky NA, Kareemi H, Parab R, et al. Incidence of primary sclerosing cholangitis: a systematic review and meta-analysis. Hepatology. 2011;53:1590–1599.PubMed Molodecky NA, Kareemi H, Parab R, et al. Incidence of primary sclerosing cholangitis: a systematic review and meta-analysis. Hepatology. 2011;53:1590–1599.PubMed
2.
go back to reference Sirpal S, Chandok N. Primary sclerosing cholangitis: diagnostic and management challenges. Clin Exp Gastroenterol. 2017;10:265–273.PubMedPubMedCentral Sirpal S, Chandok N. Primary sclerosing cholangitis: diagnostic and management challenges. Clin Exp Gastroenterol. 2017;10:265–273.PubMedPubMedCentral
3.
go back to reference Hirschfield GM, Beuers U, Corpechot C, et al. EASL Clinical Practice Guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017;67:145–172. Hirschfield GM, Beuers U, Corpechot C, et al. EASL Clinical Practice Guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017;67:145–172.
4.
go back to reference Zhu GQ, Shi KQ, Huang GQ, et al. A network meta-analysis of the efficacy and side effects of UDCA-based therapies for primary sclerosing cholangitis. Oncotarget. 2015;6:26757–26769.PubMedPubMedCentral Zhu GQ, Shi KQ, Huang GQ, et al. A network meta-analysis of the efficacy and side effects of UDCA-based therapies for primary sclerosing cholangitis. Oncotarget. 2015;6:26757–26769.PubMedPubMedCentral
6.
go back to reference Islam MA, Alam F, Solayman M, et al. Dietary phytochemicals: natural swords combating inflammation and oxidation-mediated degenerative diseases. Oxid Med Cell Longev. 2016;2016:5137431.PubMedPubMedCentral Islam MA, Alam F, Solayman M, et al. Dietary phytochemicals: natural swords combating inflammation and oxidation-mediated degenerative diseases. Oxid Med Cell Longev. 2016;2016:5137431.PubMedPubMedCentral
7.
go back to reference Morrya J, Ngamcherdtrakula W, Yantasee W. Oxidative stress in cancer and fibrosis: opportunity for therapeutic intervention with antioxidant compounds, enzymes, and nanoparticles. Redox Biol. 2017;11:240–253. Morrya J, Ngamcherdtrakula W, Yantasee W. Oxidative stress in cancer and fibrosis: opportunity for therapeutic intervention with antioxidant compounds, enzymes, and nanoparticles. Redox Biol. 2017;11:240–253.
8.
go back to reference Gharbi N, Pressac M, Hadchouel M, et al. [60] Fullerene is a powerful antioxidant in vivo with no acute or subacute toxicity. Nano Lett. 2005;5:2578–2585.PubMed Gharbi N, Pressac M, Hadchouel M, et al. [60] Fullerene is a powerful antioxidant in vivo with no acute or subacute toxicity. Nano Lett. 2005;5:2578–2585.PubMed
9.
go back to reference Lynchak OV, Prylutskyy YI, Rybalchenko VK, et al. Comparative analysis of the antineoplastic activity of C60 fullerene with 5-fluorouracil and pyrrole derivative in vivo. Nanoscale Res Lett. 2017;12:8.PubMedPubMedCentral Lynchak OV, Prylutskyy YI, Rybalchenko VK, et al. Comparative analysis of the antineoplastic activity of C60 fullerene with 5-fluorouracil and pyrrole derivative in vivo. Nanoscale Res Lett. 2017;12:8.PubMedPubMedCentral
10.
go back to reference Eswaran SV. Water soluble nanocarbon materials: a panacea for all? Curr Sci. 2018;114:1846–1850. Eswaran SV. Water soluble nanocarbon materials: a panacea for all? Curr Sci. 2018;114:1846–1850.
11.
go back to reference Prylutskyy YI, Vereshchaka IV, Maznychenko AV, et al. C60 fullerene as promising therapeutic agent for correcting and preventing skeletal muscle fatigue. J Nanobiotechnol. 2017;15:8. Prylutskyy YI, Vereshchaka IV, Maznychenko AV, et al. C60 fullerene as promising therapeutic agent for correcting and preventing skeletal muscle fatigue. J Nanobiotechnol. 2017;15:8.
12.
go back to reference Hendrickson OD, Morozova OV, Zherdev AV, et al. Study of distribution and biological effects of fullerene C60 after single and multiple intragastrical administrations to rats. Fuller Nanotub Carbon Nanostruct. 2015;23:658–668. Hendrickson OD, Morozova OV, Zherdev AV, et al. Study of distribution and biological effects of fullerene C60 after single and multiple intragastrical administrations to rats. Fuller Nanotub Carbon Nanostruct. 2015;23:658–668.
13.
go back to reference Sumner SCJ, Snyder RW, Wingard C, et al. Distribution and biomarkers of carbon-14-labeled fullerene C60 ([14C(U)]C60) in female rats and mice for up to 30 days after intravenous exposure. J Appl Toxicol. 2015;35:1452–1464.PubMedPubMedCentral Sumner SCJ, Snyder RW, Wingard C, et al. Distribution and biomarkers of carbon-14-labeled fullerene C60 ([14C(U)]C60) in female rats and mice for up to 30 days after intravenous exposure. J Appl Toxicol. 2015;35:1452–1464.PubMedPubMedCentral
14.
go back to reference Halenova TI, Vareniuk IM, Roslova NM, et al. Hepatoprotective effect of orally applied water-soluble pristine C60 fullerene against CCl4-induced acute liver injury in rats. RSC Adv. 2016;6:100046–100055. Halenova TI, Vareniuk IM, Roslova NM, et al. Hepatoprotective effect of orally applied water-soluble pristine C60 fullerene against CCl4-induced acute liver injury in rats. RSC Adv. 2016;6:100046–100055.
15.
go back to reference Byelinska IV, Kuznietsova HM, Dziubenko NV, et al. Effect of C60 fullerenes on the intensity of colon damage and hematological signs of ulcerative colitis in rats. Mater Sci Eng C. 2018;93:505–517. Byelinska IV, Kuznietsova HM, Dziubenko NV, et al. Effect of C60 fullerenes on the intensity of colon damage and hematological signs of ulcerative colitis in rats. Mater Sci Eng C. 2018;93:505–517.
17.
go back to reference Prylutskyy YI, Yashchuk VM, Kushnir KM, et al. Biophysical studies of fullerene-based composite for bio-nanotechnology. Mater Sci Eng C. 2003;23:109–111. Prylutskyy YI, Yashchuk VM, Kushnir KM, et al. Biophysical studies of fullerene-based composite for bio-nanotechnology. Mater Sci Eng C. 2003;23:109–111.
18.
go back to reference Ritter U, Prylutskyy YI, Evstigneev MP, et al. Structural features of highly stable reproducible C60 fullerene aqueous colloid solution probed by various techniques. Fuller Nanotub Carbon Nanostruct. 2015;23:530–534. Ritter U, Prylutskyy YI, Evstigneev MP, et al. Structural features of highly stable reproducible C60 fullerene aqueous colloid solution probed by various techniques. Fuller Nanotub Carbon Nanostruct. 2015;23:530–534.
19.
go back to reference Fickert P, Pollheimer MJ, Beuers U, et al. Characterization of animal models for primary sclerosing cholangitis (PSC). J Hepatol. 2014;60:1290–1303.PubMedPubMedCentral Fickert P, Pollheimer MJ, Beuers U, et al. Characterization of animal models for primary sclerosing cholangitis (PSC). J Hepatol. 2014;60:1290–1303.PubMedPubMedCentral
20.
go back to reference Bothe MK, Meyer C, Mueller U, et al. Characterization of a rat model of moderate liver dysfunction based on alpha-naphthylisothiocyanate-induced cholestasis. J Toxicol Sci. 2017;42:715–721.PubMed Bothe MK, Meyer C, Mueller U, et al. Characterization of a rat model of moderate liver dysfunction based on alpha-naphthylisothiocyanate-induced cholestasis. J Toxicol Sci. 2017;42:715–721.PubMed
21.
22.
go back to reference Cogliati B, Crespo Yanguas S, da Silva TC, et al. Connexin32 deficiency exacerbates carbon tetrachloride-induced hepatocellular injury and liver fibrosis in mice. Toxicol Mech Methods. 2016;26:362–370.PubMedPubMedCentral Cogliati B, Crespo Yanguas S, da Silva TC, et al. Connexin32 deficiency exacerbates carbon tetrachloride-induced hepatocellular injury and liver fibrosis in mice. Toxicol Mech Methods. 2016;26:362–370.PubMedPubMedCentral
23.
go back to reference Kawa S, Hamano H, Umemura T, et al. Sclerosing cholangitis associated with autoimmune pancreatitis. Hepatol Res. 2007;37:S487–S495.PubMed Kawa S, Hamano H, Umemura T, et al. Sclerosing cholangitis associated with autoimmune pancreatitis. Hepatol Res. 2007;37:S487–S495.PubMed
24.
go back to reference Valko M, Leibfritz D, Moncol J, et al. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39:44–84.PubMed Valko M, Leibfritz D, Moncol J, et al. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39:44–84.PubMed
25.
go back to reference Grattagliano I, Calamita G, Cocco T, et al. Pathogenic role of oxidative and nitrosative stress in primary biliary cirrhosis. WJG. 2014;20:5746–5759.PubMed Grattagliano I, Calamita G, Cocco T, et al. Pathogenic role of oxidative and nitrosative stress in primary biliary cirrhosis. WJG. 2014;20:5746–5759.PubMed
26.
go back to reference Prylutskyy Y, Bychko A, Sokolova V, et al. Interaction of C60 fullerene complexed to doxorubicin with model bilipid membranes and its uptake by HeLa Cells. Mater Sci Eng C. 2016;59:398–403. Prylutskyy Y, Bychko A, Sokolova V, et al. Interaction of C60 fullerene complexed to doxorubicin with model bilipid membranes and its uptake by HeLa Cells. Mater Sci Eng C. 2016;59:398–403.
27.
go back to reference Franskevych D, Palyvoda K, Petukhov D, et al. Fullerene C60 penetration into leukemic cells and its photoinduced cytotoxic effects. Nanoscale Res Lett. 2017;12:40.PubMedPubMedCentral Franskevych D, Palyvoda K, Petukhov D, et al. Fullerene C60 penetration into leukemic cells and its photoinduced cytotoxic effects. Nanoscale Res Lett. 2017;12:40.PubMedPubMedCentral
28.
go back to reference Yang H, Ramani K, Xia M, et al. Dysregulation of glutathione synthesis during cholestasis in mice: molecular mechanisms and therapeutic implications. Hepatology. 2009;49:1982–1991.PubMedPubMedCentral Yang H, Ramani K, Xia M, et al. Dysregulation of glutathione synthesis during cholestasis in mice: molecular mechanisms and therapeutic implications. Hepatology. 2009;49:1982–1991.PubMedPubMedCentral
29.
go back to reference Markiewski MM, DeAngelis RA, Lambris JD. Liver inflammation and regeneration: two distinct biological phenomena or parallel pathophysiological processes. Mol Immunol. 2006;43:45–56.PubMed Markiewski MM, DeAngelis RA, Lambris JD. Liver inflammation and regeneration: two distinct biological phenomena or parallel pathophysiological processes. Mol Immunol. 2006;43:45–56.PubMed
30.
go back to reference den Broeder AA, Verhoef LM, Fransen J, et al. Ultra-low dose of rituximab in rheumatoid arthritis: study protocol for a randomised controlled trial. Trials. 2017;18:403. den Broeder AA, Verhoef LM, Fransen J, et al. Ultra-low dose of rituximab in rheumatoid arthritis: study protocol for a randomised controlled trial. Trials. 2017;18:403.
31.
go back to reference Piróg M, Jach R, Undas A. Effects of ultra-low-dose versus standard hormone therapy on fibrinolysis and thrombin generation in postmenopausal women. Eur J Obstet Gynecol Reprod Biol. 2017;217:77–82.PubMed Piróg M, Jach R, Undas A. Effects of ultra-low-dose versus standard hormone therapy on fibrinolysis and thrombin generation in postmenopausal women. Eur J Obstet Gynecol Reprod Biol. 2017;217:77–82.PubMed
32.
go back to reference Boldyreva LB. A theoretical approach to selection of a biologically active substance in ultra-low doses for effective action on a biological system. Homeopathy. 2018;107:137–142.PubMed Boldyreva LB. A theoretical approach to selection of a biologically active substance in ultra-low doses for effective action on a biological system. Homeopathy. 2018;107:137–142.PubMed
33.
go back to reference Didenko G, Prylutska S, Kichmarenko Y, et al. Evaluation of the antitumor immune response to C60 fullerene. Mat.-wiss u Werkstofftech. 2013;44:124–128. Didenko G, Prylutska S, Kichmarenko Y, et al. Evaluation of the antitumor immune response to C60 fullerene. Mat.-wiss u Werkstofftech. 2013;44:124–128.
34.
go back to reference Turabekova M, Rasulev B, Theodore M, et al. Immunotoxicity of nanoparticles: a computational study suggests that CNTs and C60 fullerenes might be recognized as pathogens by Toll-like receptors. Nanoscale. 2014;6:3488–3495.PubMed Turabekova M, Rasulev B, Theodore M, et al. Immunotoxicity of nanoparticles: a computational study suggests that CNTs and C60 fullerenes might be recognized as pathogens by Toll-like receptors. Nanoscale. 2014;6:3488–3495.PubMed
35.
go back to reference Skivka LM, Prylutska SV, Rudyk MP, et al. C60 fullerene and its nanocomplexes with anticancer drugs modulate circulating phagocyte functions and dramatically increase ROS generation in transformed monocytes. Cancer Nanotechnol. 2018;9:8.PubMedPubMedCentral Skivka LM, Prylutska SV, Rudyk MP, et al. C60 fullerene and its nanocomplexes with anticancer drugs modulate circulating phagocyte functions and dramatically increase ROS generation in transformed monocytes. Cancer Nanotechnol. 2018;9:8.PubMedPubMedCentral
36.
go back to reference Huebener P, Schwabe RF. Regulation of wound healing and organ fibrosis by Toll-like receptors. Biochim Biophys Acta. 2013;1832:1005–1017.PubMed Huebener P, Schwabe RF. Regulation of wound healing and organ fibrosis by Toll-like receptors. Biochim Biophys Acta. 2013;1832:1005–1017.PubMed
38.
go back to reference Shershakova N, Baraboshkina E, Andreev S, et al. Anti-inflammatory effect of fullerene C60 in a mice model of atopic dermatitis. J Nanobiotechnol. 2016;14:8. Shershakova N, Baraboshkina E, Andreev S, et al. Anti-inflammatory effect of fullerene C60 in a mice model of atopic dermatitis. J Nanobiotechnol. 2016;14:8.
39.
go back to reference Libbrecht L, Roskams T. Hepatic progenitor cells in human liver diseases. Semin Cell Dev Biol. 2002;13:389–396.PubMed Libbrecht L, Roskams T. Hepatic progenitor cells in human liver diseases. Semin Cell Dev Biol. 2002;13:389–396.PubMed
40.
go back to reference Nygard IE, Mortensen KE, Hedegaard J, et al. Tissue remodelling following resection of porcine liver. Biomed Res Int. 2015;2015:248920.PubMedPubMedCentral Nygard IE, Mortensen KE, Hedegaard J, et al. Tissue remodelling following resection of porcine liver. Biomed Res Int. 2015;2015:248920.PubMedPubMedCentral
41.
go back to reference Wang S, Lee Y, Kim J, et al. Potential role of Hedgehog pathway in liver response to radiation. PLoS ONE. 2013;8:e74141.PubMedPubMedCentral Wang S, Lee Y, Kim J, et al. Potential role of Hedgehog pathway in liver response to radiation. PLoS ONE. 2013;8:e74141.PubMedPubMedCentral
42.
go back to reference Li J, Chen L, Zhang X, et al. Detection of circulating tumor cells in hepatocellular carcinoma using antibodies against asialoglycoprotein receptor, carbamoyl phosphate synthetase 1 and pan-cytokeratin. PLoS ONE. 2014;9:e96185.PubMedPubMedCentral Li J, Chen L, Zhang X, et al. Detection of circulating tumor cells in hepatocellular carcinoma using antibodies against asialoglycoprotein receptor, carbamoyl phosphate synthetase 1 and pan-cytokeratin. PLoS ONE. 2014;9:e96185.PubMedPubMedCentral
43.
go back to reference Affo S, Yu LX, Schwabe RF. The role of cancer-associated fibroblasts and fibrosis in liver cancer. Annu Rev Pathol. 2016;12:153–186.PubMedPubMedCentral Affo S, Yu LX, Schwabe RF. The role of cancer-associated fibroblasts and fibrosis in liver cancer. Annu Rev Pathol. 2016;12:153–186.PubMedPubMedCentral
44.
go back to reference Tabibian JH, Trussoni CE, O’Hara SP, et al. Characterization of cultured cholangiocytes isolated from livers of patients with primary sclerosing cholangitis. Lab Invest. 2014;94:1126–1133.PubMedPubMedCentral Tabibian JH, Trussoni CE, O’Hara SP, et al. Characterization of cultured cholangiocytes isolated from livers of patients with primary sclerosing cholangitis. Lab Invest. 2014;94:1126–1133.PubMedPubMedCentral
45.
go back to reference Chougule P, Sumitran-Holgersson S. Cytokeratins of the liver and intestine epithelial cells during development and disease. In: Hamilton G, ed. Cytokeratins—Tools in Oncology. InTech; 2012. https://doi.org/10.5772/33491. Chougule P, Sumitran-Holgersson S. Cytokeratins of the liver and intestine epithelial cells during development and disease. In: Hamilton G, ed. CytokeratinsTools in Oncology. InTech; 2012. https://​doi.​org/​10.​5772/​33491.
46.
go back to reference Ranganathan P, Jayakumar C, Manicassamy S, et al. CXCR46 knockout mice are protected against DSS-colitis-induced acute kidney injury and inflammation. Am J Physiol Renal Physiol. 2013;305:F1422–F1427.PubMedPubMedCentral Ranganathan P, Jayakumar C, Manicassamy S, et al. CXCR46 knockout mice are protected against DSS-colitis-induced acute kidney injury and inflammation. Am J Physiol Renal Physiol. 2013;305:F1422–F1427.PubMedPubMedCentral
Metadata
Title
Effects of Pristine C60 Fullerenes on Liver and Pancreas in α-Naphthylisothiocyanate-Induced Cholangitis
Authors
Halyna M. Kuznietsova
Natalia V. Dziubenko
Oksana V. Lynchak
Tetyana S. Herheliuk
Dmytro K. Zavalny
Olga V. Remeniak
Yuriy I. Prylutskyy
Uwe Ritter
Publication date
01-01-2020
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 1/2020
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-019-05730-3

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