Evaluation of toxicity of functionalized graphene with ginsenoside rh2, lysine and arginine on rbcs, blood coagulation and cardiovascular tissue: in vitro and in vivo study

Hadi Zare-zardini,1,* Asghar taheri kafrani ,2 Ahmad amiri ,3



In this study, blood and cardiotoxicity of functionalized graphene with ginsenoside rh2 (rh2), lysine and arginine was evaluated.


Rh2–treated graphene oxide (go-rh2), lysine-treated highly porous graphene (gr-lys), arginine-treated gr (gr-arg), rh2–treated gr-lys (gr-lys-rh2) and rh2–treated gr-arg (gr-arg-rh2) were synthesized. for characterization of produced nanostrcutrs, ftir, raman, and hrtem were used. after preparation, the hemolysis activity of rh2-based graphene was performed by radial diffusion and spectrophotometric assay. hemagglutination assay was performed using fresh human blood. for in vivo toxiciy assay, two concentrations of each nanostructures (200 and 1000 µg/ml) was injected to rats. after 2 weeks, the effects of agents was evaluted on heart tissue by histopathological assayes.


Results were shown that a maximum 50% hemolysis occurred in the presence of 250 μg/ml, 360 μg/ml, 420 μg/ml, 435 μg/ml, 500 μg/ml, and 575 μg/ml of go, go-rh2, go-lys, go-arg, go-lys-rh2, and go-arg-rh2, respectively. at 5-100 µg/ml, none of functionalized nanostructures cause rbc aggregation and morphological change except go. all of nanostructures had slight effect on blood coagulation system, espetially on ptt. go-arg-rh2 and go-lys-rh2 had lower effect on blood coagulation system than other examine nanosystems. between all nanostructures, go-rh2, go-arg-rh2, and go-lys-rh2 had the lowest toxicity on heart tissue.


The results of this study showed that modified go with basic aminoacids (lys and arg) and rh2 may be a potential and promising strategy to enhance the therapeutic index for graphene because of reduction of side effcets on normal cells (rbcs, heart tissue, and etc).


Arginine, cardiotoxicity, ginsenoside rh2, graphene, hemolysis, lysine