A chemically induced rat model of hemolysis with disseminated thrombosis.
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 BErelated 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 dosing, 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.
Ezov
Nathan
N
Harlan Biotech Israel Ltd, Rehovot, Israel.
Levin-Harrus
Tal
T
Mittelman
Moshe
M
Redlich
Meir
M
Shabat
Shay
S
Ward
Sandy M
SM
Peddada
Shymal
S
Nyska
Meir
M
Yedgar
Saul
S
Nyska
Abraham
A
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D005026:Ethylene Glycols / Q000633:toxicity; D005260:Female; D006461:Hemolysis / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced* / Q000473:pathology
D005026:Ethylene Glycols; C017096:n-butoxyethanol