Vega-Naredo Ignacio, Poeggeler Burkhard, Sierra-Sánchez Verónica, Caballero Beatriz, Tomás-Zapico Cristina, Alvarez-García Oscar, Tolivia Delio, Rodríguez-Colunga María J, Coto-Montes Ana
Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Asturias, Spain.
J Pineal Res. 2005 Oct;39(3):266-75. doi: 10.1111/j.1600-079X.2005.00243.x.
Quinolinic acid is a well-known excitotoxin that induces oxidative stress and damage. In the present study, oxidative damage to biomolecules was followed by measuring lipid peroxidation and protein carbonyl formation in rat brain tissue culture over a period of 24 hr of exposure to this prooxidant agent at a concentration of 0.5 mm. Quinolinic acid enhanced lipid peroxidation in an early stage of tissue culture, and protein carbonyl at a later stage. These data confirm and extend previous studies demonstrating that quinolinic acid can induce significant oxidative damage. Melatonin, an antioxidant and neuroprotective agent with multiple actions as a radical scavenger and signaling molecule, completely prevented these prooxidant actions of quinolinic acid at a concentration of 1 mm. Morphological lesions and neurotoxicity induced by quinolinic acid were evaluated by light microscopy. Quinolinic acid produced extensive apoptosis/necrosis which was significantly attenuated by melatonin. Cotreatment with melatonin exerted a profound protective effect antagonizing the neurotoxicity induced by quinolinic acid. Glutathione reductase and catalase activities were increased by quinolinic acid and these effects were antagonized by melatonin. Furthermore, melatonin induced superoxide dismutase activity. Quinolinic acid and melatonin acted independently and by different mechanisms in modulating antioxidant enzyme activities. Our findings using quinolinic acid and melatonin clearly demonstrate that such changes should always be seen in the context of oxidative neurotoxicity and antioxidant neuroprotection.
喹啉酸是一种著名的兴奋性毒素，可诱导氧化应激和损伤。在本研究中，通过在大鼠脑组织培养物中暴露于浓度为0.5 mM的这种促氧化剂24小时期间测量脂质过氧化和蛋白质羰基形成，来跟踪对生物分子的氧化损伤。喹啉酸在组织培养的早期增强脂质过氧化，在后期增强蛋白质羰基形成。这些数据证实并扩展了先前的研究，表明喹啉酸可诱导显著的氧化损伤。褪黑素是一种具有多种作用的抗氧化剂和神经保护剂，作为自由基清除剂和信号分子，在浓度为1 mM时完全阻止了喹啉酸的这些促氧化作用。通过光学显微镜评估喹啉酸诱导的形态学损伤和神经毒性。喹啉酸产生广泛的凋亡/坏死，而褪黑素可显著减轻这种情况。褪黑素与喹啉酸共同处理对喹啉酸诱导的神经毒性具有深远的保护作用。喹啉酸可增加谷胱甘肽还原酶和过氧化氢酶的活性，而这些作用可被褪黑素拮抗。此外，褪黑素可诱导超氧化物歧化酶的活性。喹啉酸和褪黑素在调节抗氧化酶活性方面独立发挥作用，且机制不同。我们使用喹啉酸和褪黑素的研究结果清楚地表明，这种变化应始终在氧化神经毒性和抗氧化神经保护的背景下看待。
