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Bioimpacts. 2019;9(4): 227-237.
doi: 10.15171/bi.2019.28
  Abstract View: 84
  PDF Download: 28

Original Research

Water-soluble pristine C60 fullerene attenuates acetaminophen-induced liver injury

Halyna Kuznietsova 1 * ORCID logo, Oksana Lynchak 1, Natalia Dziubenko 1, Tetyana Herheliuk 1, Yuriy Prylutskyy 1, Volodymyr Rybalchenko 1, Uwe Ritter 2

1 Taras Shevchenko National University of Kyiv, Institute of Biology and Medicine, 64 Volodymyrska Str., 01601 Kyiv, Ukraine
2 Technical University of Ilmenau, Institute of Chemistry and Biotechnology, 25 Weimarer Str., 98693 Ilmenau, Germany

Abstract

Introduction: Oxidative stress has been suggested as the main trigger and pathological mechanism of toxic liver injury. Effects of powerful free radical scavenger С60 fullerene on rat liver injury and liver cells (HepG2 line) were aimed to be discovered.
Methods: Acute liver injury (ALI) was simulated by single acetaminophen (APAP, 1000 mg/kg) administration, on a chronic CLI, by 4 weekly APAP administrations. Pristine C60 fullerene aqueous colloid solution (C60FAS; initial concentration 0.15 mg/mL) was administered per os or intraperitoneally at a dose of 0.5 mg/kg (ALI) or 0.25 mg/kg (CLI) daily for 2 or 28 days, respectively, after first APAP dose. Animals were sacrificed at 24th hour after the last dose. Biochemical markers of blood serum and liver autopsies were analyzed. EGFR expression in HepG2 cells after 48-hour incubation with C60FAS was assessed.
Results: Increase of serum conjugated and unconjugated bilirubin (up to 1.4-3.7 times), ALT (by 31-37%), and AST (by 18%) in non-treated ALI and CLI rats were observed, suggesting the hepatitis (confirmed by histological analysis). Liver morphological state (ALI, CLI), ALT (ALI and CLI), bilirubin (CLI), α-amylase, and creatinine (ALI) were normalized with C60FAS administration in both ways, which may indicate its protective impact on liver. However, unconjugated bilirubin sharply increased in ALI animals receiving C60FAS (up to 12 times compared to control), suggesting the augmentation of bilirubin metabolism. Furthermore, C60FAS inhibited EGFR expression in HepG2 cells in a dose-dependent manner.
Conclusion: C60FAS could partially correct acute and chronic toxic liver injury, however, it could not normalize bilirubin metabolism after acute exposure.
Keywords: C60 fullerene, Acetaminophen-induced liver injury, EGFR, HepG2 cells
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Submitted: 25 Jan 2019
Revision: 19 Mar 2019
Accepted: 16 Apr 2019
ePublished: 22 May 2019
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