Clinic of Neurology, University Clinical Centre of Nis, Bul. Dr Zorana Djindjica 48, 18000 Nis, Serbia.
J Neurol Sci. 2012 Jul 15;318(1-2):106-11. doi: 10.1016/j.jns.2012.03.015. Epub 2012 Apr 15.
We explore the nitric oxide synthase modulation by methylated arginines, asymmetric (ADMA) and symmetric (SDMA) dimethyl-l-arginine and arginase, in early phase of experimental autoimmune encephalomyelitis (EAE), the most frequently used animal model for studying the multiple sclerosis (MS), during the treatment with selective inducibile nitric oxide synthase inhibitor - aminoguanidine (AG) and oxidative scavenger N-acetyl-l-cysteine (NAC), compared to the clinical signs, continual to our previous research. The given results showed that the arginase activity was significantly increased in EAE rats compared to the healthy and AG treated EAE animals (p<0.05), and it was significantly decreased compared to the NAC treated EAE animals (p<0.05) in examined tissues. The ADMA and SDMA levels were significantly decreased in EAE untreated animals compared to the AG and NAC treated EAE animals (p<0.05). As we have reported in our previous papers, nitric oxide (NO) production, was significantly increased in examined tissues of EAE rats compared to the control group (p<0.05). In AG and NAC treated EAE group NO production was decreased in all tissues compared to untreated EAE animals (p<0.05). Also, the AG and NAC treatment of EAE rats during the development of the disease, significantly decreased the clinical score of EAE treated animals compared to EAE group. Arginase and methylated arginine derivatives, involving also NO, appear to be essential modulators of the inflammatory response in acute phase of MS. The continued research of these findings may provide a new area in the treatment of multiple sclerosis acute phase.
我们探讨了在实验性自身免疫性脑脊髓炎（EAE）的早期阶段，一氧化氮合酶（NOS）的调节，包括甲基精氨酸、不对称（ADMA）和对称（SDMA）二甲基精氨酸以及精氨酸酶。EAE 是研究多发性硬化症（MS）最常用的动物模型，我们比较了在治疗过程中使用选择性诱导型一氧化氮合酶抑制剂 - 氨基胍（AG）和氧化清除剂 N-乙酰-L-半胱氨酸（NAC）对其的影响，这与我们之前的研究结果一致。结果表明，与健康对照组和 AG 治疗的 EAE 动物相比，EAE 大鼠的精氨酸酶活性显著升高（p<0.05），与 NAC 治疗的 EAE 动物相比，其活性显著降低（p<0.05）。未经治疗的 EAE 动物的 ADMA 和 SDMA 水平明显低于 AG 和 NAC 治疗的 EAE 动物（p<0.05）。正如我们在之前的论文中报道的那样，与对照组相比，EAE 大鼠的组织中一氧化氮（NO）的产生显著增加（p<0.05）。在 AG 和 NAC 治疗的 EAE 组中，与未经治疗的 EAE 动物相比，所有组织中的 NO 产生均降低（p<0.05）。此外，在疾病发展过程中，AG 和 NAC 治疗 EAE 大鼠，可显著降低 EAE 动物的临床评分。精氨酸酶和甲基精氨酸衍生物，包括 NO，似乎是 MS 急性炎症反应的重要调节因子。对这些发现的进一步研究可能为多发性硬化症急性阶段的治疗提供一个新的领域。
