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

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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.

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Acknowledgments

The scientific results in the manuscript were presented and discussed at the 27th Annual Conference of Asian Pacific Association for the Study of the Liver (APASL 2018) that was held in New Delhi, India, at March 14–18, 2018.

Funding

This work was funded by Fundamental research grant of Ministry of Education and Science of Ukraine for young scientists “Biocompatible water-soluble C60 fullerenes as antifibrotic and antineoplastic treatment of liver malignancies” (No. 0118U000244). The funding source had no involvement in study design, the collection, analysis, and interpretation of data, the writing of the report and in the decision to submit the article for publication.

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Authors and Affiliations

  1. Institute of Biology and Medicine, Taras Shevchenko National University of Kyiv, Volodymyrska Str. 64/13, Kiev, 01601, Ukraine

    Halyna M. Kuznietsova, Natalia V. Dziubenko, Oksana V. Lynchak, Tetyana S. Herheliuk, Dmytro K. Zavalny & Yuriy I. Prylutskyy

  2. Department of Biotechnical Problems in Diagnostic, Institute for Problems of Cryobiology and Cryomedicine, Nauki Ave. 42/1, Kiev, 03028, Ukraine

    Tetyana S. Herheliuk

  3. Department of Biophysics, Informatics and Medical Equipment, National Pirogov Memorial Medical University, Vinnytsya, Pyrogova Str. 56, Vinnytsya, 21018, Ukraine

    Olga V. Remeniak

  4. Institute of Chemistry and Biotechnology, Technical University of Ilmenau, Weimarer Str. 25, 98693, Ilmenau, Germany

    Uwe Ritter

Authors
  1. Halyna M. Kuznietsova
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Correspondence to Halyna M. Kuznietsova.

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All experiments with animals’ use were conducted in compliance with bioethics principles, legislative norms, and provisions of the European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes (Strasbourg, 1986), General Ethical Principles for Experiments on Animals, adopted by the First National Bioethics Congress (Kyiv, 2001), and approved by an institutional review committee.

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Kuznietsova, H.M., Dziubenko, N.V., Lynchak, O.V. et al. Effects of Pristine C60 Fullerenes on Liver and Pancreas in α-Naphthylisothiocyanate-Induced Cholangitis. Dig Dis Sci 65, 215–224 (2020). https://doi.org/10.1007/s10620-019-05730-3

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