Erythrocytes as model cells for biocompatibility assessment, cytotoxicity screening of xenobiotics and drug delivery.

Erythrocytes (RBCs) represent the main cell component in circulation and recently have become a topic of intensive scientific interest. The relevance of erythrocytes as a model for cytotoxicity screening of xenobiotics is under the spotlight of this review. Erythrocytes constitute a fundamental cellular model to study potential interactions with blood components of manifold novel polymer or biomaterials. Morphological changes, subsequent disruption of RBC membrane integrity, and hemolysis could be used to determine the cytotoxicity of various compounds. Erythrocytes undergo a programmed death (eryptosis) which could serve as a good model for evaluating certain mechanisms which correspond to apoptosis taking place in nucleated cells. Importantly, erythrocytes can be successfully used as a valuable cellular model in examination of oxidative stress generated by certain diseases or multiple xenobiotics since red cells are subjected to permanent oxidative stress. Additionally, the antioxidant capacity of erythrocytes, and the activity of anti-oxidative enzymes could reflect reactive oxygen species (ROS) generating properties of various substances and allow to determine their effects on tissues. The last part of this review presents the latest findings on the possible application of RBCs as drug delivery systems (DDS). In conclusion, all these findings make erythrocytes highly valuable cells for in vitro biocompatibility assessment, cytotoxicity screening of a wide variety of substances as well as drug delivery.

In vitro assessment of eryptotic potential of tetrabromobisphenol A and other bromophenolic flame retardants.

Brominated flame retardants (BFRs) such as tetrabromobisphenol A (TBBPA) and tetrabromobisphenol S (TBBPS) as well as bromophenols, i.e. 2,4-dibromophenol (2,4-DBP), 2,4,6-tribromophenol (2,4,6-TBP) and pentabromophenol (PBP) have raised wide concerns due to their widespread occurrence in the environment and adverse effects observed in living organisms including human. The effect of BFRs on apoptosis of human erythrocytes has not been examined, that is why we have decided to assess eryptotic potential of these substances by determining changes in phosphatidylserine (PS) translocation, alterations in intracellular ROS and calcium ion levels, as well as caspase-3 and calpain activation in this cell type. It has been found that all BFRs studied even in the concentration of 0.001 µg/mL induced ROS formation. The compounds examined caused apoptosis by PS externalization and caspase-3 activation in human red blood cells. It has also been shown that calcium ions and calpain did not play a significant role in eryptosis induction by BFRs studied in human erythrocytes.