Red blood cell microrheological effects of some antitumor chemotherapy drugs: In vitro study

Abstract

In consequence of limitation of capillary dilatation reserve the role of erythrocyte membrane elasticity and their microrheological properties is very important for the tissue perfusion. The drugs that enter blood flow could be as signaling molecules and their action can lead to alteration of red blood cell aggregation and whole cell deformability. Therefore the subject of this study was to estimate the effect of some antitumor chemotherapy drugs on red blood cell aggregation (RBCA) and deformability (RBCD). It was found that an exposure of red blood cells (RBCs) to cisplatin and epoetin alfa led to significant positive changes in the RBC microrheological properties. It was shown that cisplatin could activate tyrosine protein kinase (TPK). Preincubation of RBCs with the inhibitor of EGF-R and Src kinase lavendustin A was accompanied by a significant decrease of the cisplatin effect. It was found RBC aggregation rise after cell incubation with 5-fluorouracil. This effect was removed with Ca2+ chelation with EGTA and also with pentoxifylline. The drug for the targeted antitumor therapy sunitinib raised RBCA markedly. Whereas RBC deformability index was altered only slightly. The combination of two chemicals: sunitinib and cisplatin led to an elimination of proaggregative effect of sunitinib. Examination of the effects of some antitumor drugs on red blood cell microrheological properties has enabled us to suggest that the observed changes in red cell aggregation and deformability may be partly related to the effects of tyrosine protein kinase activation. It is accompanied by the alteration of red blood cell microrheology and the blood transport efficacy.