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

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. 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. 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. C₆₀FAS could partially correct acute and chronic toxic liver injury, however, it could not normalize bilirubin metabolism after acute exposure.