Department of Chemistry, Faculty of Science, University of Sarajevo, Zmaja od Bosne 33-35, 71 000, Sarajevo, Bosnia and Herzegovina,
J Neural Transm (Vienna). 2015 Apr;122(4):559-64. doi: 10.1007/s00702-014-1307-y. Epub 2014 Sep 25.
Low intracerebroventricular (icv) doses of streptozotocin (STZ) produce regionally specific brain neurochemical changes in rats that are similar to those found in the brain of patients with sporadic Alzheimer's disease (sAD). Since oxidative stress is thought to be one of the major pathologic processes in sAD, catalase (CAT) activity was estimated in the regional brain tissue of animals treated intracerebroventricularly with STZ and the multitarget iron chelator, antioxidant and MAO-inhibitor M30 [5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline]. Five-day oral pre-treatment of adult male Wistar rats with 10 mg/kg/day M30 dose was followed by a single injection of STZ (1 mg/kg, icv). CAT activity was measured colorimetrically in the hippocampus (HPC), brain stem (BS) and cerebellum (CB) of the control, STZ-, M30- and STZ + M30-treated rats, respectively, 4 weeks after the STZ treatment. STZ-treated rats demonstrated significantly lower CAT activity in all three brain regions in comparison to the controls (p < 0.05 for BS and CB, p < 0.01 for HPC). M30 pre-treatment of the control rats did not influence the CAT activity in HPC and CB, but significantly increased it in BS (p < 0.05). M30 pre-treatment of STZ-treated rats significantly increased CAT activity in the HPC in comparison to the STZ treatment alone (p < 0.05) and normalized to the control values. These findings are in line with the assumption that reactive oxygen species contribute to the pathogenesis of STZ in a rat model of sAD and indicate that multifunctional iron chelators such as M30 might also have beneficial effects in this non-transgenic sAD model.
侧脑室（icv）给予低剂量链脲佐菌素（STZ）可在大鼠脑中产生与散发性阿尔茨海默病（sAD）患者脑中相似的区域性特定脑神经化学变化。由于氧化应激被认为是 sAD 主要病理过程之一，因此估计了用 STZ 和多靶点铁螯合剂、抗氧化剂和 MAO 抑制剂 M30 [5-（N-甲基-N-丙炔基氨基甲基）-8-羟基喹啉] 侧脑室给予动物后，脑内组织的过氧化氢酶（CAT）活性。10 mg/kg/天 M30 剂量连续 5 天口服预处理成年雄性 Wistar 大鼠后，给予 STZ（1 mg/kg，icv）单次注射。STZ 处理后 4 周，分别在对照组、STZ 组、M30 组和 STZ + M30 组大鼠的海马（HPC）、脑干（BS）和小脑（CB）中用比色法测量 CAT 活性。与对照组相比，STZ 处理组大鼠在所有三个脑区的 CAT 活性均显著降低（BS 和 CB 组 p <0.05，HPC 组 p <0.01）。M30 预处理对照组大鼠的 HPC 和 CB 中 CAT 活性没有影响，但显著增加了 BS 中的 CAT 活性（p <0.05）。与单独 STZ 处理相比，M30 预处理 STZ 处理组大鼠的 HPC 中 CAT 活性显著增加（p <0.05），并恢复至对照组水平。这些发现与假设一致，即活性氧物种有助于 sAD 大鼠模型中 STZ 的发病机制，并表明多功能铁螯合剂如 M30 可能在这种非转基因 sAD 模型中也具有有益作用。
