A chemically induced rat model of hemolysis with disseminated thrombosis

Nathan Ezov, Tal Levin-Harrus, Moshe Mittelman, Meir Redlich, Shay Shabat, Sandy M. Ward, Shymal Peddada, Meir Nyska, Saul Yedgar, Abraham Nyska*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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, lungs, 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.

Original languageEnglish
Pages (from-to)181-193
Number of pages13
JournalCardiovascular Toxicology
Volume2
Issue number3
DOIs
StatePublished - 2002
Externally publishedYes

Funding

FundersFunder number
National Institute of Environmental Health SciencesZ01ES045005

    Keywords

    • 2-Butoxyethanol
    • Heart
    • Hemolysis
    • Infarct
    • Rat model
    • Thrombosis

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