title: 2-Butoxyethanol female-rat model of hemolysis and disseminated thrombosis: X-ray characterization of osteonecrosis and growth-plate suppression.
abstract: 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.
authors.affiliation: Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709-9998, USA.
authors.forename: Danielle N
authors.initials: DN
authors.lastname: Lewis
authors.forename: Abraham
authors.initials: A
authors.lastname: Nyska
authors.forename: Kennita
authors.initials: K
authors.lastname: Johnson
authors.forename: David E
authors.initials: DE
authors.lastname: Malarkey
authors.forename: Sandy
authors.initials: S
authors.lastname: Ward
authors.forename: Michael
authors.initials: M
authors.lastname: Streicker
authors.forename: Shay
authors.initials: S
authors.lastname: Shabat
authors.forename: Shyamal
authors.initials: S
authors.lastname: Peddada
authors.forename: Meir
authors.initials: M
authors.lastname: Nyska
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000000981:diagnostic imaging; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced* / Q000150:complications / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005026:Ethylene Glycols / Q000633:toxicity*; D005260:Female; D006132:Growth Plate / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D010020:Osteonecrosis / Q000139:chemically induced* / Q000209:etiology / Q000473:pathology; D011859:Radiography / Q000295:instrumentation; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D012997:Solvents / Q000633:toxicity*
chemical_list: D005026:Ethylene Glycols; D012997:Solvents; C017096:n-butoxyethanol