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2-Butoxyethanol enhances the adherence of red blood cells

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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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References

  • Barker JE, Wandersee NJ (1999) Thrombosis in heritable hemolytic disorders. Curr Opin Hematol 6:71–75

    Article  CAS  PubMed  Google Scholar 

  • Ben-Ami R, Barshtein G, Zeltser D, Goldberg Y, Shapira I, Roth A Keren G, Miller H, Prochorov V, Eldor A, Berliner S, Yedgar S (2001) Parameters of red blood cell aggregation as correlates of the inflammatory state. Am J Physiol Heart Circ Physiol 280:H1982–H1988

    CAS  PubMed  Google Scholar 

  • Borgna Pignatti C, Carnelli V, Caruso V, Dore F, De Mattia D, Di Palma A, Di Gregorio F, Romeo MA, Longhi R, Mangiagli A, Melevendi C, Pizzarelli G, Musumeci S (1999) Thromboembolic events in beta thalassemia major: an Italian multicenter study. Acta Haematol 99:76–79

    Article  Google Scholar 

  • Chen S, Barshtein G, Gavish B, Mahler Y, Yedgar S (1994) Monitoring of red blood cell aggregability by computerized imaging. Clin Hemorheology 14:497–508

    Google Scholar 

  • Chen S, Gavish B, Zhang S, Mahler Y, Yedgar S (1995) Monitoring of erythrocyte aggregate morphology under flow by computerized image analysis. Biorheology 32:487–496

    Article  CAS  PubMed  Google Scholar 

  • Chen S, Eldor A, Barshtein G, Zhang S, Goldfarb A, Rachmilewitz E, Yedgar S (1996) Enhanced aggregability of red blood cells of beta-thalassemia major patients. Am J Physiol 270:H1951–H1956

    CAS  PubMed  Google Scholar 

  • Chien S (1987) Physiological and pathophysiological significance of hemorheology. In Chien S, Dormandi J, Ernst E, Matrai A (eds) Clinical hemorheology. Nijhoff, Dordrecht, pp 125–164

  • Demiroglu H (1997) The importance of erythrocyte aggregation in blood rheology: considerations on the pathophysiology of thrombotic disorders. Blood 89:4236

    CAS  PubMed  Google Scholar 

  • Eldor A, Maclouf J, Lellouche F, Ben-Yashar V, Barenholz Y, Durst R, Hy-Am E, Goldfarb A, Rachmilewitz E (1993) A chronic hypercoagulable state and life-long platelet activation in beta thalassemia major. Southeast Asian J Trop Med Public Health 24 Suppl 1:92–95

    Google Scholar 

  • Eldor A, Durst R, Hy-Am E, Goldfarb A, Gillis S, Rachmilewitz EA, Abramov A, MacLouf J, Godefray YC, De Raucourt E, Guillin MC (1999) A chronic hypercoagulable state in patients with beta-thalassaemia major is already present in childhood. Br J Haematol 107:739–746

    Article  CAS  PubMed  Google Scholar 

  • Ezov N, Levin-Harrus T, Mittelman M, Redlich M, Shabat S, Ward SM, Peddada S, Nyska M, Yedgar S, Nyska A (2002) Chemically induced rat model of hemolysis with disseminated thrombosis. Cardiovasc Toxicol 2:181–194

    PubMed  Google Scholar 

  • Ghanayem BI (1989) Metabolic and cellular basis of 2-butoxyethanol-induced hemolytic anemia in rats and assessment of human risk in vitro. Biochem Pharmacol 38:1679–1684

    Article  CAS  PubMed  Google Scholar 

  • Ghanayem BI (1996) An overview of the hematotoxicity of ethylene glycol ethers. Occup Med 2:253–268

    CAS  Google Scholar 

  • Ghanayem BI, Sullivan CA (1993) Assessment of the hemolytic activity of 2-butoxyethanol and its major metabolite, butoxyacetic acid, in various mammals including humans. Hum Exp Toxicol 12:305–311

    CAS  PubMed  Google Scholar 

  • Ghanayem BI, Blair PC, Thompson HB, Maronpot RR, Matthews HB (1987a) Effect of age on the toxicity and metabolism of ethylene glycol monobutyl ether (2-butoxyethanol) in rats. Toxicol Appl Pharmacol 91:222–234

    CAS  PubMed  Google Scholar 

  • Ghanayem BI, Burka LT, Matthews HB (1987b) Metabolic basis of ethylene glycol monobutyl ether (2-butoxyethanol) toxicity: role of alcohol and aldehyde dehydrogenases. J Pharmacol Exp Ther 242:222–231

    CAS  PubMed  Google Scholar 

  • Ghanayem BI, Sanchez IM, Matthews HB (1992) Development of tolerance to 2-butoxyethanol-induced hemolytic anemia and studies to elucidate the underlying mechanisms. Toxicol Appl Pharmacol 112:198–206

    CAS  PubMed  Google Scholar 

  • Ghanayem BI, Ward SM, Chanas B, Nyska A (2000) Comparison of the acute hematotoxicity of 2-butoxyethanol in male and female F344 rats. Hum Exp Toxicol 19:185–192

    Article  CAS  PubMed  Google Scholar 

  • Ghanayem BI, Long PH, Ward SM, Chanas B, Nyska M, Nyska A (2001) Hemolytic anemia, thrombosis, and infarction in male and female F344 rats following gavage exposure to 2-butoxyethanol. Exp Toxicol Pathol 53:97–105

    CAS  PubMed  Google Scholar 

  • Grossblatt N (ed) (1996) Guide for the care and use of laboratory animals. National Academy, Washington

  • Hovav T, Goldfarb A, Artmann G, Yedgar S, Barshtein G (1999) Enhanced adherence of beta-thalassaemic erythrocytes to endothelial cells. Br J Haematol 106:178–181

    CAS  PubMed  Google Scholar 

  • Jones JG (1990) New aspects of red cell aggregation. J R Soc Med 83:663–664

    Google Scholar 

  • Kaul DK, Nagel RL (1993) Sickle cell vasoocclusion: many issues and some answers. Experientia 49:5–15

    CAS  PubMed  Google Scholar 

  • Koshkaryev A, Barshtein G, Yedgar S (2001) Red blood cell-endothelial cells interaction in oxidative stress states. Proceeding of the 7thWorld Congress for Microcirculation (Sydney, Australia). Monduzzi, Bologna

  • Logothetis J, Constantoulakis M, Economidou J, Stefanis C, Hakas P, Augoustaki O, Sofroniadou K, Loewenson R, Bilek M (1972) Thalassemia major (homozygous beta-thalassemia). A survey of 138 cases with emphasis on neurologic and muscular aspects. Neurology 22:294–304

    CAS  PubMed  Google Scholar 

  • Mohandas N, Chasis JA (1993) Red blood cell deformability, membrane material properties and shape: regulation by transmembrane, skeletal and cytosolic proteins and lipids. Semin Hematol 30:171–192

    CAS  PubMed  Google Scholar 

  • Nyska A, Maronpot RR, Long PH, Hailey RJ, Travlos GS, Roycroft JH, Ghanayem BI (1999) Disseminated thrombosis and bone infarction in female rats following inhalation exposure to 2-butoxyethanol. Toxicol Pathol 27:287–294

    CAS  PubMed  Google Scholar 

  • Setty BN, Stuart MJ (1996) Vascular cell adhesion molecule-1 is involved in mediating hypoxia-induced sickle red blood cell adherence to endothelium: potential role in sickle cell disease. Blood 88:2311–2320

    CAS  PubMed  Google Scholar 

  • Shiu YT, Udden MM, McIntire LV (2000) Perfusion with sickle erythrocytes up-regulates ICAM-1 and VCAM-1 gene expression in cultured human endothelial cells. Blood 95:3232–3241

    PubMed  Google Scholar 

  • Udden MM (2000) Rat erythrocyte morphological changes after gavage dosing with 2-butoxyethanol: a comparison with the in vitro effects of butoxyacetic acid on rat and human erythrocytes. J Appl Toxicol 20:381–387

    Article  CAS  PubMed  Google Scholar 

  • Udden MM (2002) In vitro sub-hemolytic effects of butoxyacetic acid on human and rat erythrocytes. Toxicol Sci 69:258–264

    Article  CAS  PubMed  Google Scholar 

  • Wautier JL, Wautier MP, Schmidt AM, Anderson GM, Hori O, Zoukourian C, Capron L, Chappey O, Yan SD, Guillausseau P, Stern D (1994) Advanced glycation end products (AGEs) on the surface of diabetic erythrocytes bind to the vessel wall via a specific receptor inducing oxidant stress in the vasculature: a link between surface-associated AGEs and diabetic complications. Proc Natl Acad Sci USA 91:7742–7746

    CAS  PubMed  Google Scholar 

  • Yedgar S, Hovav T, Barshtein G (1999) Red blood cell intercellular interactions in oxidative stress states. Clin Hemorheol Microcirc 21:189–193

    CAS  PubMed  Google Scholar 

Download references

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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Correspondence to Abraham Nyska.

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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

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