Abstract
We recently presented a unique, chemically-induced rat model of hemolytic anemia and disseminated thrombosis. In this 2-butoxyethanol (BE)-induced model the organs developing infarction are comparable to those seen in human diseases, characterized by hemolysis and thrombosis (e.g., thalassemia, sickle-cell disease, paroxysmal nocturnal hemoglobinuria, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome). Red blood cells (RBCs) have special flow properties, namely, self-aggregability, deformability, and potential adherence to endothelial cells (ECs) of the blood vessel wall, which are essential for adequate blood flow and tissue perfusion; their alteration facilitates circulatory disorders. To examine the possible contribution of alterations in RBC flow properties to the observed thrombosis in the present investigation we determined the BE-induced changes in adherence, aggregability, and deformability of RBCs from male and female Fischer F344 rats exposed to two, three, or four daily doses of BE at 250 mg BE/kg body weight. Control animals were treated with the vehicle alone. Blood was taken on days 2, 3, 4, and 29. The administration of BE did not affect the RBCs aggregability but markedly enhanced their adherence to extracellular matrix; such enhancement was correlated with adherence to cultured ECs. RBC/EC interaction has been shown to be a potent catalyst of vascular occlusion in hemolytic hemoglobinopathies; thus the enhanced RBC adherence to EC is a likely mechanism by which thrombosis and organ infarct are induced in BE-treated rats.
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Acknowledgements
The authors gratefully acknowledge Ms. JoAnne Johnson, Dr. June Dunnick, and Sandy Ward from the NIEHS for their critical review of the manuscript. We are indebted to O. Fredman for technical assistance. This study was supported by a grant to S.Y. and G.B. from the United States–Israel Binational Science Foundation (#2001203).
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This investigation is dedicated to the memory of Professor Amiram Eldor
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Koshkaryev, A., Barshtein, G., Nyska, A. et al. 2-Butoxyethanol enhances the adherence of red blood cells. Arch Toxicol 77, 465–469 (2003). https://doi.org/10.1007/s00204-003-0471-x
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DOI: https://doi.org/10.1007/s00204-003-0471-x