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Evaluation of bone toxicity in various bones of aged rats
Authors:Noguchi Chihiro  Miyata Hiroto  Sato Yasushi  Iwaki Yoshinobu  Okuyama Shigeru
Institution:Drug Safety and Pharmacokinetics Laboratories, Taisho Pharmaceutical Co., Ltd., 403 Yoshino-cho 1, Kita-ku, Saitama-shi, Saitama 331-9530, Japan.
Abstract:The aim of the present study was to provide a method for evaluating bone toxicity induced by drugs in various bones in aged rats. Male Crl:CD (SD) rats at 46 weeks of age were administered 15 mg/m(2) body surface area of doxorubicin, which effects the growth plate in weanling rats, weekly for 9 weeks by intravenous injection, and the femur, sternum, humerus and tibia were examined histopathologically. In the doxorubicin-treated group, thinning of the growth plate was remarkably observed in the proximal tibia and humerus; however, these changes were not observed in other regions. In addition, the osteoclast number per bone perimeter in the proximal tibia was significantly higher than others in control aged rat. Thus, recognizing the various histological reactions related to the time of epiphyseal closure is important for evaluating bone toxicity in aged rats.
Keywords:bone toxicity  rat  growth plate  epiphyseal closure  doxorubicin
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