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

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.

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

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.