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2-Butoxyethanol Female-Rat Model of Hemolysis and Disseminated Thrombosis: X-Ray Characterization of Osteonecrosis and Growth-Plate Suppression
1 Laboratory of Experimental Pathology Correspondence: Address correspondence to: Dr. Abraham Nyska, Laboratory of Experimental Pathology, MD B3-06, National Institute of Environmental Health Sciences, 111 T. W. Alexander Drive, Research Triangle Park, North Carolina 27709-9998, USA; e-mail:nyska{at}niehs.nih.gov. We recently proposed a chemically induced rat model for human hemolytic disorders associated with thrombosis. The objective of the present investigation was to apply a noninvasive, high-magnification X-ray analysis, the Faxitron radiography system, to characterize the protracted bone damage associated with this 2-butoxyethanol model and to validate it by histopathology. Groups of female Fischer 344 rats were given 0, 250, or 300 mg of 2-butoxyethanol/kg body weight daily for 4 consecutive days. Groups were then sacrificed 2 hours or 26 days after the final treatment. The treated animals displayed a darkened purple-red discoloration on the distal tail. Histopathological evaluation, including phosphotungstic acid-hematoxylin staining of animals sacrificed 2 hours after the final treatment, revealed disseminated thrombosis and infarction in multiple organs, including bones. The Faxitron MX-20 specimen radiography system was used to image selected bones of rats sacrificed 26 days posttreatment. Premature thinning of the growth plate occurred in the calcaneus, lumbar and coccygeal vertebrae, femur, and ilium of the treated animals. Areas of decreased radiographic densities were seen in the diaphysis of the femur of all treated animals. The bones were then examined histologically and showed a range of changes, including loss or damage to growth plates and necrosis of cortical bone. No thrombi were seen in the animals sacrificed at 30 days, but bone and growth plate changes consistent with prior ischemia were noted. The Faxitron proved to be an excellent noninvasive tool that can be used in future studies with this animal model to examine treatment modalities for the chronic effects of human thrombotic disorders.
Key Words: 2-Butoxyethanol • hemolysis • thrombosis • osteonecrosis • growth plate • ischemia Abbreviations: BAA, 2-butoxyacetic acid • BE, 2-butoxyethanol • H&E, hematoxylin and eosin • Hct, hematocrit • Hgb, hemoglobin • MCH, mean cell hemoglobin • MCHC, mean cell hemoglobin concentration • MCV, mean cell volume • MRI, magnetic resonance imaging • NBF, neutral buffered formalin • PCV, packed cell volume • PTAH, phosphotungstic acid-hematoxylin • RBC, red blood cells • WBC, white blood cells
Toxicologic Pathology, Vol. 33, No. 2,
272-282 (2005) |
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