The prepared C60FAS was characterized by AFM and DLS techniques

The prepared C60FAS was characterized by AFM and DLS techniques. The AFM study of C60 fullerene film deposited from an aqueous solution revealed a high degree of molecule dispersion in solution. to interact with epidermal, vasoendothelial, platelet-derived, and fibroblast growth factor receptors (EGFR, VEGFR, PDGFR, and FGFR, respectively) was estimated by computational modeling. We observed that C60FAS reduced the severity of fibrosis in fibrotic rats (0.75 vs. 3.0 points according to Ishak score), attenuated the hepatocyte injury, normalized elevated blood serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and mitigated oxidative stress manifestation in liver tissue restoring its redox balance. When applied to cirrhotic animals, C60FAS reduced connective tissue deposition as well (2.4 vs. 5.4 points according to Ishak score), diminished ALP and LDH (by 16% and 61%), and normalized conjugated and nonconjugated bilirubin, restoring the liver function. Altered liver lipid and protein peroxides and glutathione peroxidase activity were also leveled. Within a computer simulation, it was shown that C60 fullerenes can block hinge prohibiting ATP binding for EGFR and FGFR and thus blocking associated signal pathways. This ability in addition to their antioxidant properties may contribute to C60 fullerene’s antifibrotic action. Thus, C60FAS may have a substantial therapeutic potential as an inhibitor of liver fibrosis and cirrhosis. 1. Introduction Liver cirrhosis is the end-stage condition of YM348 a wide variety of chronic liver diseases and an increasing cause of morbidity and mortality worldwide. Its 1-year mortality ranges from 1% to 57% depending on the stage. To date, the only treatment of developed cirrhosis is liver transplantation [1]. Liver fibrosis, as a pathological process, is characterized by the growth of connective tissue without changing the gland structure wherein the liver lobules are not altered, but YM348 there are wide bands of fibrous connective tissue around them. The cirrhosis develops during fibrosis progress: the liver lobes become replaced with connective tissue with the formation of cirrhotic nodes. This YM348 leads to a significant decrease in the liver functional activity and the development of liver failure. Furthermore, liver fibrosis and cirrhosis are considered as main risk factors of nonviral etiology of IL23R antibody hepatocellular carcinoma (HCC) development. Thus, HCC arises from chronic liver inflammation, fibrosis, and eventually cirrhosis in 70-80% of instances [2]. Liver fibrosis is an excessive healing with the formation of an excess amount of connective cells incorporated into the liver parenchyma. This process is accompanied by extracellular matrix overproduction and/or its incomplete degradation [3]. The liver chronic injury is the result in of fibrogenesis. Usually, it is accompanied by excessive production of reactive oxygen varieties (ROS), lipid peroxidation products, and proinflammatory cytokines, which cause activation of hepatic stellate cells (HSCs) that proliferate with the formation of myofibroblasts. Hence, oxidative stress can play a key part in HSC activation, fibrogenesis initiation, progression, and transition to cirrhosis [4]. HSCs after becoming activated require growth factors for his or her proliferation, as any cells do. Indeed, growth element receptor signaling is essential for HSC proliferation and subsequent liver fibrogenesis and attracts the attention as promising target of antifibrotic treatment [5, 6]. The main YM348 etiological factors of liver fibrosis and cirrhosis are as follows: alcohol, storage diseases, hepatitis viruses, and hepatotoxic medicines. There is no specific remedy for liver fibrosis to day. Some compounds having restorative activity against liver fibrosis are undergoing preclinical and I-II phases of medical tests. They include (1) the monoclonal antibodies and low molecular inhibitors of important signaling pathways involved in the regulation of swelling, HSC life cycle, and collagen rate of metabolism [7] (however, these substances are highly specific, i.e., target the only link of a separate signaling pathway) and (2) the broad-spectrum providers exhibiting.