Toxicity of the C60 fullerene aqueous colloid solution in vitro and in vivo experiments was studied. C60 fullerene in the concentration range of 3.6-144 µg/mL demonstrated low toxicity against human embryonic kidney (HEK293) cells with 383.4 μg/mL IC50 value. The acute toxicity of C60 fullerene in a dose progression (75, 150, 300, 600, 1200 and 1800 mg/kg) was investigated at 14th day after single intraperitoneal (i.p.) administration into mice. No toxic effect of С60 fullerene in the dose range of 75-150 mg/kg was observed; the calculated LD50 value was 721 mg/kg. The toxic effect of C60 fullerene was observed at a concentration of 300 mg/kg and higher, it was accompanied with mice behavior disturbance, hematotoxicity and pathomorphological changes in spleen, hepatic and kidney tissues. In mice treated with 600 mg/kg of C60 fullerene indices of inflammatory process were detected, whereas at 1200 mg/kg dose leukopoies and thrombocytopoies were found to be suppressed. Thus, C60 fullerene aqueous colloid solution in a dose range of 75-150 mg/kg is nontoxic and could be used for biomedical purposes.
1 January 2018 in Oxidative Medicine and Cellular Longevity
The effects of C60FAS (50 and 500 μg/kg) supplementation, in a normal physiological state and after restraint stress exposure, on prooxidant/antioxidant balance in rat tissues were explored and compared with the effects of the known exogenous antioxidant N‐acetylcysteine. Oxidative stress biomarkers (ROS, O2⋅−, H2O2, and lipid peroxidation) and indices of antioxidant status (MnSOD, catalase, GPx, GST, γ‐GCL, GR activities, and GSH level) were measured in the brain and the heart. In addition, protein expression of Nrf2 in the nuclear and cytosol fractions as well as the protein level of antiradical enzyme MnSOD and GSH‐related enzymes γ‐GCLC, GPx, and GSTP as downstream targets of Nrf2 was evaluated by western blot analysis. Under a stress condition, C60FAS attenuates ROS generation and O2⋅− and H2O2 releases and thus decreases lipid peroxidation as well as increases rat tissue antioxidant capacity. We have shown that C60FAS supplementation has dose‐dependent and tissue‐specific effects. C60FAS strengthened the antiradical defense through the upregulation of MnSOD in brain cells and maintained MnSOD protein content at the control level in the myocardium. Moreover, C60FAS enhanced the GSH level and the activity/protein expression of GSH‐related enzymes. Correlation of these changes with Nrf2 protein content suggests that under stress exposure, along with other mechanisms, the Nrf2/ARE‐antioxidant pathway may be involved in regulation of glutathione homeostasis. In our study, in an in vivo model, when C60FAS (50 and 500 μg/kg) was applied alone, no significant changes in Nrf2 protein expression as well as in activity/protein levels of MnSOD and GSH‐related enzymes in both tissues types were observed. All these facts allow us to assume that in the in vivo model, C60FAS affects on the brain and heart endogenous antioxidative statuses only during the oxidative stress condition.
Fullerene C60 as a representative of carbon nanocompounds is suggested to be promising agent for application in photodynamic therapy due to its unique phys
Growth experiments of transplanted malignant tumors in the presence of water-soluble C60 fullerenes were performed on groups of mice. It was found that C60 fullerenes efficiently inhibit the growth of transplanted malignant tumors. This behavior can be explained through their high antioxidant activity and the blocking of the specific cell receptors (for example, endothelial growth factor). The findings demonstrate the possibility of using C60 fullerenes in anticancer therapy.