Cytotoxic and toxicological characteristics of oxidation-reduction dendrimers

Introduction. Oxidation-reduction dendrimers can produce anion-radicals, that is singlet oxygen and hydrogen peroxide. In this study toxicity of newly synthesized REDOX-dendrimer (RD) in mammalian cells in vitro and in vivo were preliminary evaluated. Objective: toxicity assessment of new RD for mammalian cells in vitro and in vivo. Materials and methods. Cytotoxicity studies of RD was made with MTT and direct living cells counting methods in Syrian hamster embryonic fibroblasts, modified with Src gene (HETR-SR); Syrian hamster embryonic fibroblasts, modified with NRAS gene (HEТR-NRAS); Chinese hamster ovary cancer cell line CHO-K1; erythroid human leukosis K562 and it’s subclone K562/iS9. In vivo toxicity was evaluated in healthy BDF mice using single intraperitoneal injection. Results. RD studies showed that it effectively influences cell lines with different catalase activity. 50 % growth inhibition (1C_%) was observed at concentration of RD: 6,871E-09- 7,031E-09 М - for HEТR-NRAS; 1,64E-08-1,78E-08 М - for HETR-SR; 2,92E-08- 3,06E-08 M-for СНО-К1 strain. For K562/iS9 and К562 IC₅₀ value was within the range from 1,698Е-005 to 2,606Е-005 М and from 1,288Е-005 to 1,722Е-005 М, respectively. Acute toxicity studies in mice showed that LD₁₀ = 948 + 4 mg/kg and LD₅₀ = 1000 + 21 (958 - 1043) mg/kg. Conclusion. New RD was studied in this research both in vitro and in vivo. It’s toxic parameters were determined in mammalian cells with different catalase strength. Obtained values of IC₅₀ ≤10^-4 М show that studied RD is cytotoxic. Acute toxicity studies in mice showed that RD influence on animals is dose dependant.

REDOX-дендример, цитотоксичность, токсикология, REDOX-dendrimer, cytotoxity, toxicology