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A chemically induced rat model of hemolysis with disseminated thrombosis

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Abstract

Although hemolytic anemia and thrombosis, which can be serious or even lethal, are often encountered in daily common practice., their pathogenesis has remained obscure, partially because of the absence of appropriate models. Here we present a unique chemically induced rat model of hemolytic anemia and disseminated thrombosis in which the organs developing infarction are comparable to those seen in humans. We exposed male and female Fischer F344 rats to two, three, or four daily doses of 2-butoxyethanol (BE) at 250 mg/kg body weight and examined for hemolysis and histopathological evidence of disseminated thrombosis on d 2, 3, 4, and 29. Time-course BE-related erythrocytic changes were statistically significant in both sexes. Evidence of thrombosis and infarction was seen mainly in females dosed more than once with widespread thrombotic crisis after two or three dosings, likely explicable by the more significant morphological changes in erythrocytes and hemolysis observed in this gender. We documented thrombosis and infarction in the heart, brain, Jungs, eyes, and bones. Our model with its list of target organs similar to that observed in human diseases characterized by hemolysis and thrombosis [for example, thalassemia, sickle cell disease (SCD), paroxysmal nocturnal hemoglobinuria (PNF), disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), and hemolytic uremic syndrome (HUS)] suggests that it can be an excellent tool to study the pathogenesis of such complications.

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Author information

Authors and Affiliations

  1. Harlan Biotech Israel Ltd., Kiryat Weizmann, Bld. 13B, 76326, Rehovot, Israel

    Nathan Ezov & Tal Levin-Harrus

  2. Department of Internal Medicine “B”, Rabin Medical Center-Hasharon Hospital, Petah-Tikva, Israel

    Moshe Mittelman

  3. Department of Orthodontics, Faculty of Dental Medicine, Hebrew University-Hadassah Medical School, Jerusalem, Israel

    Meir Redlich

  4. Orthopaedic Surgery Department, Sapir Medical Center, Kfar-Saba, Israel

    Shay Shabat & Meir Nyska

  5. Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, MD B3-06, 111 T.W. Alexander Drive, P.O. Box 12233, 27709-9998, Research Triangle Park, NC

    Sandy M. Ward & Abraham Nyska

  6. Department of Biostatistics, National Institute of Environmental Health Sciences (NIEHS), 27709, Research Triangle Park, NC

    Shymal Peddada

  7. Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel

    Saul Yedgar

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  1. Nathan Ezov
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  2. Tal Levin-Harrus
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  8. Meir Nyska
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  10. Abraham Nyska
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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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Ezov, N., Levin-Harrus, T., Mittelman, M. et al. A chemically induced rat model of hemolysis with disseminated thrombosis. Cardiovasc Toxicol 2, 181–193 (2002). https://doi.org/10.1007/s12012-002-0003-6

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