Age and dose sensitivities in the 2-butoxyethanol F344 rat model of hemolytic anemia and disseminated thrombosis.

Abstract

In hemolytic disorders, such as sickle cell disease and beta-thalassemia, the mechanisms of thrombosis are poorly understood. Appropriate animal models would increase the understanding of the pathophysiology of thrombosis. We previously reported that rats exposed to 2-butoxyethanol (2-BE) developed hemolytic anemia and disseminated thrombosis resembling sickle cell disease and beta-thalassemia. To characterize our model further, we investigated age- and dose-related differences in sensitivity to 2-BE. We exposed groups of 6- and 12-week-old F344 rats (5 animals/group) to 62.5, 125, and 250 mg/kg/day of 2-BE for up to 4 days. Blood was collected on days 2-4 for complete blood count and measurement of intracellular adhesion molecule-1 (ICAM-1). Histopathological evaluation was performed to find evidence of disseminated thrombosis. The maximum hemolytic response, resulting in decreased erythrocyte count and higher mean cell volume (MCV) occurred in the 12-week-old rats treated with the highest dose of 2-BE (250 mg/kg, p<0.0001). The highest increase in ICAM-1 levels occurred in the 12-week-old rats treated with 125 and 250 mg/kg 2-BE (p<0.0001). No intravascular thrombi were noted in the 6-week-old 2-BE-treated animals. The majority of intravascular thrombi occurred in the 12-week-old rats treated with 250 mg/kg 2-BE. Because our findings show age- and dose-related sensitivities, we suggest that 12-week-old rats and doses of 250 mg/kg be used in the 2-BE model.

• Authors: Yuval Ramot, Deborah A Lewis, Thomas L Ortel, Mike Streicker, Glenda Moser, Susan Elmore, Sandra M Ward, Shyamal Peddada, Abraham Nyska
• Journal: Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie (Exp Toxicol Pathol) Vol. 58 Issue 5 Pg. 311-22 (Apr 2007) ISSN: 0940-2993 [Print] Germany
• PMID: 17261363 (Publication Type: Journal Article)

Chemical References

• Ethylene Glycols
• Intercellular Adhesion Molecule-1
• n-butoxyethanol

Topics

• Aging (blood)
• Anemia, Hemolytic (blood, chemically induced)
• Animals
• Disease Models, Animal
• Disseminated Intravascular Coagulation (blood, chemically induced)
• Dose-Response Relationship, Drug
• Erythrocyte Count
• Erythrocyte Indices
• Erythrocytes (cytology, drug effects)
• Ethylene Glycols (pharmacology)
• Intercellular Adhesion Molecule-1 (metabolism)
• Rats
• Rats, Inbred F344
• Thrombosis (blood, chemically induced)