Department of Philosophical and Methodological Disciplines, University Health Sciences Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico.
Department of Chemistry, University Center of Exact Sciences and Engineering, University of Guadalajara, Guadalajara 44430, Jalisco, Mexico.
Molecules. 2022 Jun 30;27(13):4217. doi: 10.3390/molecules27134217.
Experimental autoimmune encephalomyelitis (EAE) is a relevant animal model of multiple sclerosis (MS). Oxidative stress and chronic inflammation play a major role in the pathogenesis of MS and EAE. Melatonin, a neurohormone, has potent anti-inflammatory properties. The aim of our study was to assess the therapeutic properties of melatonin alone or in combination with interferon β-1b (IFNβ-1b) or glatiramer acetate (GA) on EAE. EAE was induced in male Sprague-Dawley rats with an intraperitoneal injection of a homogenate of spinal cord and pig brain. At day 10 post immunization, rats were euthanized, and their brains were immediately excised and processed to measure oxidative stress markers and membrane fluidity. In addition, proinflammatory cytokines were quantified in plasma. Melatonin alone or in combination with GA and IFNβ-1b inhibited the disease process of EAE and the synthesis of proinflammatory cytokines, caused a significant decrement in oxidative stress markers, and preserved the membrane fluidity in the motor cortex, midbrain, and spinal cord. The cumulative index score was significantly reduced in EAE rats treated with melatonin alone or in combination with GA and IFNβ-1b. In conclusion, our findings provide preclinical evidence for the use of melatonin as an adjuvant therapeutic treatment for MS.
实验性自身免疫性脑脊髓炎（EAE）是多发性硬化症（MS）的相关动物模型。氧化应激和慢性炎症在 MS 和 EAE 的发病机制中起主要作用。褪黑素作为一种神经激素，具有强大的抗炎特性。我们的研究目的是评估褪黑素单独或与干扰素β-1b（IFNβ-1b）或醋酸格拉替雷（GA）联合应用于 EAE 的治疗特性。通过腹腔注射脊髓和猪脑匀浆在雄性 Sprague-Dawley 大鼠中诱导 EAE。在免疫后 10 天，处死大鼠，立即取出大脑并进行处理，以测量氧化应激标志物和膜流动性。此外，还定量了血浆中的促炎细胞因子。褪黑素单独或与 GA 和 IFNβ-1b 联合使用可抑制 EAE 的疾病进程和促炎细胞因子的合成，显著降低氧化应激标志物，并在运动皮层、中脑和脊髓中保持膜流动性。单独使用褪黑素或与 GA 和 IFNβ-1b 联合使用的 EAE 大鼠的累积指数评分显著降低。总之，我们的研究结果为褪黑素作为 MS 的辅助治疗提供了临床前证据。
