• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of applied toxicology >Effect of structural modifications on 3 (3,5-dichlorophenyl) 2, 4-thiazolidinedione-induced hepatotoxicity in Fischer 344 rats
【24h】

Effect of structural modifications on 3 (3,5-dichlorophenyl) 2, 4-thiazolidinedione-induced hepatotoxicity in Fischer 344 rats

机译：三（3,5-二氯苯基）2，4-噻唑烷二酮诱导的肝毒性在Fischer 344大鼠中的影响

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

摘要

ABSTRACT: Glitazones, used for type II diabetes, have been associated with liver damage in humans. A structural feature known as a 2,4-thiazolidinedione (TZD) ring may contribute to this toxicity. TZD rings are of interest since continued human exposure via the glitazones and various prototype drugs is possible. Previously, we found that 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione (DCPT) was hepatotoxic in rats. To evaluate the importance of structure on DCPT toxicity, we therefore studied two series of analogs. The TZD ring was replaced with: a mercaptoacetic acid group {[[[(3,5-dichlorophenyl)amino] carbonyl]thio]acetic acid, DCTA}; a methylated TZO ring [3-(3,5-dichlorophenyl)-5-methyl-2,4-thiazolidinedione, DPMT]; and isomeric thiazolidinone rings [3-(3,5-dichlorophenyl)-2- and 3-(3,5-dichlorophenyl)-4-thiazolidinone, 2-DCTD and 4-DCTD, respectively]. The following phenyl ring-modified analogs were also tested: 3-phenyl-, 3-(4-chlorophenyl)-, 3-(3,5-dimethylphenyl)- and 3-[3,5-bis(trifluoromethyl)phenyl]-2,4-thiazolidinedione (PTZD, CPTD, DMPT and DFMPT, respectively). Toxicity was assessed in male Fischer 344 rats 24 h after administration of the compounds. In the TZD series only DPMT produced liver damage, as evidenced by elevated serum alanine aminotransferase (ALT) activities at 0.6 and 1.0 mmol kg"1 (298.6 +-176.1 and 327.3 +-102.9 Sigma-Frankel units ml~(-1) respectively) vs corn oil controls (36.0 +-11.3) and morphological changes in liver sections. Among the phenyl analogs, hepatotoxicity was observed in rats administered PTZD, CPTD and DMPT; with ALT values of 1196.2 +-133.6, 1622.5 +-218.5 and 2071.9 +-217.8, respectively (1.0 mmol kg~(-1) doses). Morphological examination revealed severe hepatic necrosis in these animals. Our results suggest that hepatotoxicity of these compounds is critically dependent on the presence of a TZD ring and also the phenyl substituents.
机译：摘要：用于II型糖尿病的Gliitazones与人类的肝损伤有关。称为2,4-噻唑烷二酮（TZD）环的结构特征可能有助于这种毒性。由于持续通过峡谷和各种原型药物持续的人体暴露，TZD环非常感兴趣。以前，我们发现3-（3,5-二氯苯基）-2,4-噻唑烷二酮（DCPT）在大鼠中是肝毒性。为了评估结构对DCPT毒性的重要性，因此研究了两种类似物。 TZD环被替代：巯基乙酸基团（[[（3,5-二氯苯基）氨基]羰基]乙酸，DCTA};甲基化的TZO环[3-（3,5-二氯苯基）-5-甲基-2,4-噻唑烷基，DPMT];和异构噻唑烷酮环[3-（3,5-二氯苯基）-2-和3-（3,5-二氯苯基）-4-噻唑烷酮，2-DCTD和4-DCTD]。还测试以下苯基环改性类似物：3-苯基，3-（4-氯苯基） - ，3-（3,5-二甲基苯基） - 和3- [3,5-双（三氟甲基）苯基] - 2,4-噻唑烷二酮（PTZD，CPTD，DMPT和DFMPT）。在给予化合物后24小时在雄性费斯344大鼠中评估毒性。在TZD系列中，只有DPMT产生的肝损伤，如0.6和1.0mmol kg“1（298.6 + -176.1和327.3 + -102.9 sigma-frankel单位ml〜（-1）的升高的血清丙氨酸氨基转移酶（ALT）活性所证明玉米油控制（36.0±11.3）和肝脏部分的形态变化。在苯基类似物中，在施用PTZD，CPTD和DMPT的大鼠中观察到肝毒性; ALT值为1196.2 + -133.6,1622.5 + -218.5和2071.9 + -217.8分别（1.0mmol kg〜（-1）剂量）。形态学检查显示这些动物的严重肝脏坏死。我们的研究结果表明这些化合物的肝毒性依赖于TZD环和苯基取代基的存在。 。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
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