Nanochemistry and biotechnology
Comparative effects of water-soluble С60 fullerenes and protein kinase inhibitor on rat liver under colon cancer model 

Chereschuk I.O. 1, Kuznietsova H.M.1, Dziubenko N.V.1, Lynchak O.V.1, Prylutskyy Yu.I.1, Rybalchenko V.K.1, Scharff P.2, Ritter U.2 

1Taras Shevchenko National University of Kyiv, Volodymyrska str., 64/13, 01601, Kyiv, Ukraine; E-mail: richairis@gmail.com 
2Ilmenau University of Technology, Institute of Chemistry and Biotechnology, Weimarer str. 25, 98693 Ilmenau, Germany

To date cancer is one of the most problems of Humanity. It is known that fullerene C60 nanostructures due to their physical-chemical properties are powerful antioxidants enabling them to possess anti-inflammatory and anti-tumor effects with relatively low toxicity in in vitro and in vivo systems [1]. Protein kinase inhibitors are high-specific and low-toxic cytostatics. So their combined action could be the promising strategy for cancer treatment. 
The effects of water-soluble biocompatible С60 fullerenes (C60FAS) on liver function under rat colon cancer model were aimed to be discovered. The model was simulated by 20 1,2-dimethylhydrazine weekly injections, then tumor development followed for 7 weeks and animals were treated with C60FAS (0,5 mg/kg per injection, total received dose 10 mg/kg), or protein kinase inhibitor 1-(4-Cl-benzyl)-3-chloro-4-CF3-phenylamino)-1H-pyrrole-2,5-dione (MI) (2,7 mg/kg daily), or those combined. The liver state was assessed by microscopic (hematoxylin-eosin staining) and biochemical (plasma blood ALT, AST, total and direct bilirubin) methods.
Non-treated rats demonstrated liver inflammatory features, vascular endothelium thickening, thrombosis and fibrosis, ALT and AST growth (by 11 and 24%). However, bilirubin levels remained constant, suggesting the liver function retention. Colonic tumor lesions number were reduced under all treatments (by 30-50%). However, liver reactions were different: in C60FAS group inflammatory and fibrotic features persisted, ALT and AST remained elevated. MI normalized aminotransferases activity and inhibited inflammation, but not fibrosis. Combined action of C60FAS and MI caused AST (by 43%) and direct bilirubin (by 90%) growth, however, diminished inflammation and connective tissue expansion.
Thus, C60FAS and MI acting simultaneously cause quite different effects on liver compared with their separate impact: as C60FAS didn’t improve liver state and MI inhibited inflammation and normalized function, as those combined affect the liver function but normalized its morphology. 
1.	Prylutska S.V. Matyshevska O.P., Grynyuk I.I. et al. Biological effects of C60 fullerenes in vitro and in a model system//Mol Cryst Liq Cryst.-2007.-468: 265-274.