Bostanci M Omer, Bağirici Faruk, Canan Sinan
Department of Physiology, Faculty of Medicine, University of Ondokuz Mayis, 55139, Samsun, Turkey.
Cell Biol Toxicol. 2006 Mar;22(2):119-25. doi: 10.1007/s10565-006-0037-9. Epub 2006 Mar 9.
Iron is a metal highly concentrated in liver and brain tissue, and known to induce neuronal hyperactivity and oxidative stress. It has been established that iron levels rise in the brain in some neurodegenerative diseases such as Parkinson's and Alzheimer's diseases (AD). A body of evidence indicates a link between neuronal death and intracellular excessive calcium accumulation. The aim of the present study was to investigate the effects of a calcium antagonist, flunarizine, on neurotoxicity induced by intracerebroventricular (i.c.v.) iron injection. For this reason rats were divided into three groups as control, iron and iron+flunarizine groups. Animals in iron and iron+flunarizine groups received i.c.v. FeCl(3) injection (200 mM, 2.5 microl), while control rats received the same amount of saline into the cerebral ventricles. Rats in iron+flunarizine group also received i.c.v. flunarizine (1 microM, 2 microl) following FeCl(3) injection. All animals were kept alive for ten days following the operation and animals in iron+flunarizine group received intraperitoneal (i.p.) flunarizine injections once a day (10 mg/kg/day) during this period. After ten days, rats were sacrificed. The total numbers of neurons in hippocampus of all rats were estimated with the latest, unbiased stereological techniques. Findings of the present study suggest that flunarizine may attenuate the neurotoxic effects of iron injection by inhibiting the cellular influx of excessive calcium ions.
铁是一种在肝脏和脑组织中高度浓缩的金属，已知会诱发神经元活动亢进和氧化应激。已经确定，在某些神经退行性疾病如帕金森病和阿尔茨海默病（AD）中，大脑中的铁含量会升高。大量证据表明神经元死亡与细胞内过量钙积累之间存在联系。本研究的目的是探讨钙拮抗剂氟桂利嗪对脑室内（i.c.v.）注射铁诱导的神经毒性的影响。因此，将大鼠分为三组，即对照组、铁组和铁+氟桂利嗪组。铁组和铁+氟桂利嗪组的动物接受脑室内注射FeCl₃（200 mM，2.5微升），而对照组大鼠则向脑室注射等量的生理盐水。铁+氟桂利嗪组的大鼠在注射FeCl₃后还接受脑室内注射氟桂利嗪（1 microM，2微升）。术后所有动物均存活10天，在此期间，铁+氟桂利嗪组的动物每天接受一次腹腔内（i.p.）注射氟桂利嗪（10 mg/kg/天）。10天后，处死大鼠。使用最新的、无偏倚的体视学技术估计所有大鼠海马体中的神经元总数。本研究结果表明，氟桂利嗪可能通过抑制过量钙离子的细胞内流入来减轻铁注射的神经毒性作用。
