Pharmacology Division, Indo Soviet College of Pharmacy, Moga-142001, India; Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India.
Eur J Pharmacol. 2013 Dec 5;721(1-3):373-81. doi: 10.1016/j.ejphar.2013.08.016. Epub 2013 Sep 25.
Oxidative-nitrosative stress and mitochondrial dysfunction plays an important role in the onset of various neurodegenerative diseases. Lycopene, a carotenoid antioxidant, has received considerable scientific interest in recent years. Present study was designed to evaluate the possible nitric oxide mechanism in protective effects of lycopene against the colchicine induced cognitive impairment and mito-oxidative damage in rats. Wistar rats were received i.c.v. colchicine (15 µg/5 µl). Lycopene (2.5 and 5mg/kg), NO modulators e.g. l-Arginine (50mg/kg) l-NAME (5mg/kg) administered for 21 days. Behavioural alterations were assessed in between study period. Animals were killed immediately following the last behavioral session, and mitochondrial enzymes, oxidative parameters, inflammatory mediators (TNF-α, IL-6) and caspase-3 activity were measured. I.C.V. administration of colchicine impaired memory performance in Morris water maze, oxidative defense and mitochondrial complex enzymes activities as compared to sham group. A significant increase of TNF-α, IL-6 and caspase-3 activity in hippocampus and cortex was also noted. Chronic treatment lycopene significantly improved memory retention and attenuated mito-oxidative damage parameters, inflammatory markers and apoptosis in colchicine treated rats. Further, l-arginine pretreatment with sub effective dose of lycopene significantly reversed the protective effect of lycopene. However, l-NAME pretreatment with sub effective dose of lycopene significantly potentiated the protective effect of lycopene which was significant as compared to their effect per se. These results suggest that lycopene exhibit a neuroprotective effect by accelerating brain anti-oxidant defense mechanisms and down regulating nitric oxide pathways. Thus, lycopene may be used as therapeutic agent in preventing complications in memory dysfunction.
氧化应激和线粒体功能障碍在各种神经退行性疾病的发病机制中起着重要作用。番茄红素作为一种类胡萝卜素抗氧化剂，近年来受到了相当多的科学关注。本研究旨在评估番茄红素对 colchicine 诱导的大鼠认知障碍和线粒体氧化损伤的保护作用的可能的一氧化氮机制。Wistar 大鼠接受 icv colchicine（15µg/5µl）。番茄红素（2.5 和 5mg/kg）、NO 调节剂，如 l-精氨酸（50mg/kg）和 l-NAME（5mg/kg），连续给药 21 天。在研究期间评估行为改变。最后一次行为测试后，动物立即处死，测量线粒体酶、氧化参数、炎症介质（TNF-α、IL-6）和 caspase-3 活性。与假手术组相比，icv 给予 colchicine 可损害 Morris 水迷宫中的记忆表现、氧化防御和线粒体复合酶活性。还观察到海马体和皮质中 TNF-α、IL-6 和 caspase-3 活性显著增加。慢性番茄红素治疗可显著改善记忆保留，并减轻 colchicine 处理大鼠的线粒体氧化损伤参数、炎症标志物和细胞凋亡。此外，预先给予 l-精氨酸（亚有效剂量的番茄红素）可显著逆转番茄红素的保护作用。然而，预先给予 l-NAME（亚有效剂量的番茄红素）可显著增强番茄红素的保护作用，与它们本身的作用相比具有统计学意义。这些结果表明，番茄红素通过加速大脑抗氧化防御机制和下调一氧化氮途径来发挥神经保护作用。因此，番茄红素可用作预防记忆功能障碍并发症的治疗剂。
