Takamatsu Kazuhiko, Yamashita Hiroyuki, Satake Shigeru, Kazusa Katsuyuki, Tabata Hajime, Nishikata Takahito
Drug Safety Research Laboratories, Astellas Pharma Inc., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan.
Exp Anim. 2015;64(3):269-80. doi: 10.1538/expanim.14-0098. Epub 2015 Mar 30.
This study was conducted to examine any changes caused by feed restriction in dogs to contribute to safety evaluation in toxicity studies. Two male 7-month-old beagle dogs/group were fed 300 (control), 150 (50% of control), or 70 g/animal of diet daily (23% of control) for 4 weeks. Effects of feed restriction, except for clinical signs, were noted depending on the feed dosage in almost all examinations. The principal outcomes were: decreased body weight and water consumption, ECG changes (decreased heart rate and prolonged QTc), and hematopoietic and lymphopoietic suppression (decreased reticulocyte ratio or white blood cell count in hematology, decreased nucleated cell count in bone marrow, decreased erythroid parameters in myelography, and hypocellularity of bone marrow and thymic atrophy in histopathology). In addition, some changes were noted in urinalysis (decreased urine volume and sodium and potassium excretion), blood chemistry (decreased ALP and inorganic phosphorus and increased creatinine), organ weights, and gastric histopathology. These results provide important reference data for distinguishing the primary effects of test compounds from secondary effects of decreased food consumption in toxicity studies in beagle dogs.
本研究旨在检测犬只饲料限制所引起的任何变化，以有助于毒性研究中的安全性评估。每组两只7月龄雄性比格犬，分别每日喂食300克（对照组）、150克（对照组的50%）或70克/只的日粮（对照组的23%），持续4周。在几乎所有检查中，除临床症状外，饲料限制的影响根据饲料剂量而有所不同。主要结果包括：体重和饮水量下降、心电图变化（心率降低和QTc延长）、造血和淋巴细胞生成抑制（血液学中网织红细胞比例或白细胞计数降低、骨髓中有核细胞计数降低、骨髓造影中红系参数降低、组织病理学中骨髓细胞减少和胸腺萎缩）。此外，尿液分析（尿量、钠和钾排泄减少）、血液化学（碱性磷酸酶和无机磷降低、肌酐升高）、器官重量和胃组织病理学也有一些变化。这些结果为在比格犬毒性研究中区分受试化合物的主要作用与食物摄入量减少的次要作用提供了重要的参考数据。
