Raheja K L, Linscheer W G, Cho C
Comp Biochem Physiol C Comp Pharmacol Toxicol. 1986;85(2):397-400. doi: 10.1016/0742-8413(86)90215-x.
An animal model for clinically observed clofibrate (p-chlorophenoxy isobutyrate, CPIB)-induced toxicity has been tested. It is demonstrated that propylthiouracil-induced hypothyroid-hyperlipidemic chick develops severe toxic manifestations following clofibrate administration. Toxic symptoms are characterized by listlessness, drowziness, and extreme muscular weakness. This is associated with elevation of blood urea nitrogen, creatine phosphokinase, uric acid and glutamic oxaloacetic transaminase. Histological examination of muscle specimen from chicks exhibiting toxic syndrome showed degeneration and vacuolization of muscle fibers. The biochemical and histological changes observed are quite similar to those reported in clinical practice in some patients given clofibrate. It is suggested that this chick model could be used to investigate the biochemical basis of clofibrate toxicity.
已对一种用于临床观察到的氯贝丁酯(对氯苯氧异丁酸,CPIB)诱导毒性的动物模型进行了测试。结果表明,丙硫氧嘧啶诱导的甲状腺功能减退-高脂血症雏鸡在给予氯贝丁酯后会出现严重的毒性表现。毒性症状的特征为无精打采、嗜睡和极度肌肉无力。这与血尿素氮、肌酸磷酸激酶、尿酸和谷草转氨酶升高有关。对表现出毒性综合征的雏鸡肌肉标本进行组织学检查,显示肌纤维变性和空泡化。观察到的生化和组织学变化与临床实践中一些服用氯贝丁酯的患者所报告的变化非常相似。建议该雏鸡模型可用于研究氯贝丁酯毒性的生化基础。