Bergeron R J, Streiff R R, Wiegand J, Vinson J R, Luchetta G, Evans K M, Peter H, Jenny H B
Department of Medicinal Chemistry, Medicine University of Florida, Gainesville 32610.
Ann N Y Acad Sci. 1990;612:378-93. doi: 10.1111/j.1749-6632.1990.tb24325.x.
A comparative study of the non-iron-overloaded, bile duct-cannulated rat and of the Cebus monkey as iron-clearance models is presented. The ability of desferrioxamine, desferrithiocin, and a pyridoxal isonicotinoyl hydrazone (PIH) analogue to clear the metal from these two animals is evaluated. Data suggest that although rodents represent a viable first-line animal screen, there is no strict correspondence between the effectiveness of a chelator in rodents and that in primates. Rodent data should be interpreted carefully as it relates to potential human trials. Iron-loading response, the similarity between multiple human and Cebus serum and hematological values, and the ability to easily observe changes in behavioral patterns clearly render the Cebus monkey the best preclinical screen.
本文介绍了非铁过载、胆管插管大鼠和卷尾猴作为铁清除模型的比较研究。评估了去铁胺、去铁硫素和一种吡哆醛异烟酰腙(PIH)类似物从这两种动物体内清除金属的能力。数据表明,尽管啮齿动物是可行的一线动物筛选模型,但螯合剂在啮齿动物和灵长类动物中的有效性之间没有严格的对应关系。啮齿动物的数据在涉及潜在人体试验时应谨慎解读。铁负荷反应、多个人类和卷尾猴血清及血液学值之间的相似性,以及轻松观察行为模式变化的能力,显然使卷尾猴成为最佳的临床前筛选模型。