The Antitumor and Toxicity Effects of Ruthenium(II) Complexes on Heterotopic Murine Colon Carcinoma Model

Abstract

Abstract The aim of the present study was to examine the antitumor and toxicity effects of ruthenium(II) complexes, [Ru(Cltpy)(en)Cl][Cl] (Ru-1) and [Ru(Cl-tpy)(dach)Cl][Cl] (Ru-2) on heterotopic murine colon carcinoma model. For tumor induction, 1×106 CT26 cells suspended in 100 μl of DMEM were injected subcutaneously into flank of male BALB/c mice. Treatment groups were as follows: Ru-1, Ru-2, oxaliplatin and control (saline). The intraperitoneal administration of the tested complexes began on 6th day after CT26 cells inoculation. Each complex was administered at dose of 5 mg/kg, twice weekly, four doses in total. To assess toxicity, serum values of urea, creatinine, AST and ALT were determined and histopathological analysis of organs and tumor were performed. In order to assess the effects of Ru(II) complexes on markers of oxidative stress and antioxidant defense system, we determined the TBARS, GSH, SOD and CAT in the homogenate of tumor, heart, liver, lungs and kidney tissues. The findings indicate that Ru-1 and Ru-2 exerts equal or better antitumor activity in comparison with oxaliplatin, but with pronounced toxic effects such as reduced survival rate, cardiotoxicity, nephrotoxicity and hepatotoxicity. The increased index of lipid peroxidation in the tissues of the kidneys and heart, but decreased in tumor tissue, after Ru(II) complexes administration, indicates the importance of the induction of oxidative stress as a possible mechanism of nephrotoxicity and cardiotoxicity, but not the mechanism by which they realize antitumor activity. Additional studies are needed to elucidate the mechanism of antitumor activity and toxicity of the Ru(II) complexes.