Toovey Stephen
Royal Free and University College Medical School, London, UK; Travel Clinic, Cape Town, South Africa.
Toxicol Lett. 2006 Oct 10;166(2):95-104. doi: 10.1016/j.toxlet.2006.06.001. Epub 2006 Jun 7.
In vitro, animal, and human clinical studies suggest currently deployed artemisinins possess neurotoxic potential. A specific and consistent pattern of brainstem injuries that includes auditory processing centers has been reported from all laboratory animals studied. Hearing loss, ataxia, and tremor are reported from humans. Neurotoxicity appears mediated in part through artemisinin induced oxidative stress in exposed brainstems. In vitro studies suggest that artemisinin neurotoxicity does not manifest immediately upon exposure, but that once commenced it is inevitable and irreversible; extrapolation from in vitro data suggests that 14 days may possibly be required for full development, casting doubt upon some animal safety studies and human necropsy studies. Uncertainty remains over the neurotoxicity of currently deployed artemisinins, and their safety profile should be reviewed, especially in pediatric use. The development of non-neurotoxic artemisinins is possible and should be encouraged.
体外、动物和人体临床研究表明，目前使用的青蒿素具有神经毒性潜力。在所有研究的实验动物中，均报告了包括听觉处理中枢在内的特定且一致的脑干损伤模式。人类中也有听力丧失、共济失调和震颤的报告。神经毒性似乎部分是由青蒿素诱导暴露脑干中的氧化应激介导的。体外研究表明，青蒿素神经毒性在暴露后不会立即显现，但一旦开始就不可避免且不可逆转；从体外数据推断，可能需要14天才能完全显现，这对一些动物安全性研究和人体尸检研究提出了质疑。目前使用的青蒿素的神经毒性仍存在不确定性，其安全性概况应予以审查，尤其是在儿科使用中。开发无神经毒性的青蒿素是可能的，应该予以鼓励。
