Valero Nereida, MarinaEspina Luz, Bonilla Ernesto, Mosquera Jesus
Seccion de Virologia, Instituto de Investigaciones Clinicas Dr. Americo Negrette, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela.
J Pineal Res. 2007 Mar;42(2):107-12. doi: 10.1111/j.1600-079X.2006.00381.x.
Melatonin, a potent antioxidant, has shown to be beneficial in murine Venezuelan equine encephalomyelitis (VEE) virus infection. In addition, melatonin can induces the production of interleukin-1 beta (IL-1beta), a cytokine capable of inducing increased expression of inducible nitric oxide synthase; the activity of this enzyme is increased in the brain of mice infected with VEE virus. The aim of this study was to determine the effect of VEE virus on the nitric oxide (NO) production, lipid peroxidation and IL-1beta production in the brain and serum of mice infected with VEE virus, and to investigate the modulatory role of melatonin during this viral infection. Mice were infected with 10 LD(50) of VEE virus and treated with melatonin (500 microg/kg of body weight) starting 3 days before and continuing for 5 days after virus inoculation. Mice were sacrificed on days 1, 3 and 5 postinfection and brains and blood samples were obtained. NO and IL-1beta production and lipid peroxidation levels were measured in perfused brain homogenates and serum. Increased production of brain nitrite was found on days 1, 3 and 5 postinfection and lipid peroxidation products were increased at day 5. Levels of serum nitrite were found elevated on days 3 and 5 postinfection; however, lipid peroxidation products remained similar to basal levels. Melatonin treatment decreased nitrite concentration in brain and serum of infected mice as well as the lipid peroxidation products in the brain. IL-1beta was found to be increased in the brain and serum of infected animals, and melatonin treatment induced higher levels of this cytokine (brain: about 4-fold; serum: about 8-fold). These results may be related to the beneficial effect of melatonin in the VEE experimental disease and address the possible therapeutic potential of the indoleamine in human VEE virus infection.
褪黑素是一种强效抗氧化剂，已证明其对小鼠委内瑞拉马脑炎（VEE）病毒感染有益。此外，褪黑素可诱导白细胞介素 - 1β（IL - 1β）的产生，IL - 1β是一种能够诱导诱导型一氧化氮合酶表达增加的细胞因子；在感染VEE病毒的小鼠大脑中，该酶的活性会增加。本研究的目的是确定VEE病毒对感染VEE病毒小鼠的大脑和血清中一氧化氮（NO）产生、脂质过氧化和IL - 1β产生的影响，并研究褪黑素在这种病毒感染过程中的调节作用。小鼠感染10倍半数致死量（LD50）的VEE病毒，并在病毒接种前3天开始用褪黑素（500微克/千克体重）治疗，并在接种后持续5天。在感染后第1、3和5天处死小鼠，获取大脑和血液样本。在灌注的脑匀浆和血清中测量NO、IL - 1β的产生以及脂质过氧化水平。在感染后第1、3和5天发现脑中亚硝酸盐产生增加，在第5天脂质过氧化产物增加。在感染后第3和5天发现血清亚硝酸盐水平升高；然而，脂质过氧化产物仍与基础水平相似。褪黑素治疗降低了感染小鼠大脑和血清中的亚硝酸盐浓度以及大脑中的脂质过氧化产物。发现感染动物的大脑和血清中IL - 1β增加，褪黑素治疗诱导该细胞因子水平更高（大脑：约4倍；血清：约8倍）。这些结果可能与褪黑素在VEE实验性疾病中的有益作用有关，并揭示了这种吲哚胺在人类VEE病毒感染中可能的治疗潜力。
