...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>BioMetals: An International Journal on the Role of Metal Ions in Biology, Biochemistry and Medicine >LIVER IRON DEPLETION AND TOXICITY OF THE IRON CHELATOR DEFERIPRONE (L-1, CP20) IN THE GUINEA PIG
【24h】

LIVER IRON DEPLETION AND TOXICITY OF THE IRON CHELATOR DEFERIPRONE (L-1, CP20) IN THE GUINEA PIG

机译：LIVER IRON DEPLETION AND TOXICITY OF THE IRON CHELATOR DEFERIPRONE (L-1, CP20) IN THE GUINEA PIG

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相关主题

摘要

The use of the iron chelator deferiprone (L-1, CP20, 1,2-dimethyl-3-hydroxypyrid-4-one) for the treatment of diseases of iron overload and other disorders is problematic and requires further evaluation. In this study the efficacy, toxicity and mechanism of action of orally administered L-1 were investigated in the guinea pig using the carbonyl iron model of iron overload. In an acute trial, depletion of liver non-heme iron in drug-treated guinea pigs (normal iron status) was maximal (approximately 50% of control) after a single oral dose of L-1 of 200 mg kg(-1), suggesting a limited chelatable pool in normal tissue. There was no apparent toxicity up to 600 mg kg(-1). In each of two sub-acute trials, normal and iron-loaded animals were fed L-1 (300 mg kg(-1) day(-1)) or placebo for six days. Final mortalities were 12/20 (L-1) and 0/20 (placebo). Symptoms included weakness, weight loss and eye discharge. Iron-loaded as well as normal guinea pigs were affected, indicating that at this drug level iron loading was not protective. In a chronic trial guinea pigs received L-1 (50 mg kg(-1) day(-1)) or placebo for six days per week over eight months. Liver non-heme iron was reduced in animals iron-loaded prior to the trial. The increase in a wave latency (electroretinogram), the foci of hepatic, myocardial and musculo-skeletal necrosis, and the decrease in white blood cells in the drug-treated/normal diet group even at the low-dose of 50 mg kg(-1) day(-1) suggests that L-1 may be unsuitable for the treatment of diseases which do not involve Fe overload. However, the low level of pathology in animals treated with iron prior to the trial suggests that even a small degree of iron overload (two-fold after eight months) is protective at this drug level. We conclude that the relationship between drug dose and iron status is critical in avoiding toxicity and must be monitored rigorously as cellular iron is depleted. [References: 41]

著录项

获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号