Department of Medical Biochemistry, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey.
Department of Medical Biochemistry, Faculty of Medicine, Duzce University, 81620, Duzce, Turkey.
Neurochem Res. 2019 Aug;44(8):2020-2029. doi: 10.1007/s11064-019-02839-9. Epub 2019 Jun 29.
The neurotoxic effects of aluminum are generally associated with reduced antioxidant capacity, increased oxidative stress and apoptosis, which lead to the induction of neurodegenerative processes. Curcumin has a lipophilic polyphenol character and effects of antioxidant and anti-apoptotic. The present study was undertaken to examine possible aluminum exposure in rats brain synaptosomes and to investigate whether protective and therapeutic effects of curcumin on biochemical and morphological changes in both pre- and post-treated groups. Aluminum chloride (AlCl) at 50 µM concentration and curcumin at 5 and 10 µg/mL doses were applied to hippocampal synaptosomes of rats according to experimental design. Biochemical effects were evaluated by MTT cytotoxicity, malondialdehyde (MDA) levels, nitric oxide (NO) levels, glutathione (GSH) levels, caspase 3 activities, cytochrome c levels, DNA fragmentation values and protein levels. Morphological examinations were done by TEM analysis. AlCI exposure in the synaptosomes enhanced oxidative stress, triggered apoptosis and caused ultrastructural alterations which were well reflected in the TEM images. Curcumin pre-treatment slightly ameliorated the MDA levels, NO levels, cytochrome c levels and caspase 3 activities in AlCI-exposed synaptosomes, but these results were not statistically significant. Furthermore, curcumin post-treatment significantly improved oxidative damage and morphological alterations, and suppressed cytochrome c and caspase 3 activities. Taken together, our data showed that curcumin had more therapeutic effects than protective effects in AlCI-induced neurotoxicity. Nevertheless, the therapeutic (post-protective) effects of curcumin should be further investigated in in vivo neurodegenerative models involving behavioral tests.
铝的神经毒性作用通常与抗氧化能力降低、氧化应激和细胞凋亡增加有关,这会导致神经退行性过程的诱导。姜黄素具有亲脂性多酚特性,具有抗氧化和抗细胞凋亡作用。本研究旨在检查大鼠脑突触体中可能的铝暴露,并研究姜黄素对预处理和后处理组生化和形态变化的保护和治疗作用。根据实验设计,将 50μM 浓度的氯化铝(AlCl)和 5 和 10μg/mL 剂量的姜黄素应用于大鼠海马突触体。通过 MTT 细胞毒性、丙二醛(MDA)水平、一氧化氮(NO)水平、谷胱甘肽(GSH)水平、半胱天冬酶 3 活性、细胞色素 c 水平、DNA 片段化值和蛋白质水平评估生化效应。形态学检查通过 TEM 分析进行。AlCI 在突触体中的暴露增强了氧化应激,引发了细胞凋亡,并导致超微结构改变,这些改变在 TEM 图像中得到了很好的反映。姜黄素预处理略微改善了 AlCI 暴露的突触体中的 MDA 水平、NO 水平、细胞色素 c 水平和半胱天冬酶 3 活性,但这些结果没有统计学意义。此外,姜黄素后处理显著改善了氧化损伤和形态改变,并抑制了细胞色素 c 和半胱天冬酶 3 的活性。总之,我们的数据表明,姜黄素在 AlCI 诱导的神经毒性中具有更多的治疗作用而不是保护作用。然而,姜黄素的治疗(后保护)作用应该在涉及行为测试的体内神经退行性模型中进一步研究。