Yamada Takashi, Nakaoka Ryusuke, Sawada Rumi, Matsuoka Atsuko, Tsuchiya Toshie
Division of Medical Devices, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
J Nanosci Nanotechnol. 2010 Jan;10(1):604-11. doi: 10.1166/jnn.2010.1720.
Fullerenes are condensed ring aromatic compounds with extended pi systems; they have unique cage structures. Current studies suggest that several fullerene derivatives have neuroprotective effects, and it is expected that fullerenes will be useful in drug delivery system and novel medical devices targeting the brain. However, little is known about the effects of fullerenes and its derivative on brain function. We examined the effect of fullerene(OH)24 on the central nervous system in this study. In a V79 colony assay, the IC50 of fullerene(OH)24 was 1.74 microg/ml. In an MTT assay, fullerene(OH)24 reduced proliferation of normal human astrocytes obviously. In an vivo study, 0.25 mg/kg(-1) of fullerene(OH)24 was injected into the lateral ventricle of rat brains. The intracerebral injection of fullerene(OH)24 remarkably decreased body weight and locomotor behavior of rats on day 1, but drastically increased locomotor behavior on day 7. The intracerebral injection of fullerene(OH)24 changed the monoamine concentration greatly on day 1 and slightly on day 30 after the injection. These results suggest that intracerebral injection of fullerene(OH)24 had strong and acute effects on the central nervous system, but that the effects were not permanent. In conclusion, we suggest that fullerene's derivative, fullerene(OH)24 had toxic effects on brain cells and that intracerebral injection of fullerene(OH)24 had acute harmful effects on brain monoamines neurotransmission and locomotor activity.
富勒烯是具有扩展π体系的稠环芳香化合物；它们具有独特的笼状结构。目前的研究表明，几种富勒烯衍生物具有神经保护作用，并且预计富勒烯将用于药物递送系统和针对大脑的新型医疗器械。然而，关于富勒烯及其衍生物对脑功能的影响知之甚少。在本研究中，我们检测了富勒烯(OH)24对中枢神经系统的影响。在V79集落试验中，富勒烯(OH)24的IC50为1.74微克/毫升。在MTT试验中，富勒烯(OH)24明显降低了正常人星形胶质细胞的增殖。在一项体内研究中，将0.25毫克/千克(-1)的富勒烯(OH)24注入大鼠脑侧脑室。脑内注射富勒烯(OH)24在第1天显著降低了大鼠的体重和运动行为，但在第7天显著增加了运动行为。脑内注射富勒烯(OH)24在注射后第1天极大地改变了单胺浓度，在第30天略有改变。这些结果表明，脑内注射富勒烯(OH)24对中枢神经系统有强烈而急性的影响，但这些影响不是永久性的。总之，我们认为富勒烯的衍生物富勒烯(OH)24对脑细胞有毒性作用，并且脑内注射富勒烯(OH)24对脑单胺神经传递和运动活动有急性有害影响。
