Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, 160014, India.
Psychopharmacology (Berl). 2009 Dec;207(2):257-70. doi: 10.1007/s00213-009-1652-y. Epub 2009 Sep 18.
The role of oxidative stress has been well known in neurodegenerative disorders. 3-Nitropropionic acid (3-NP) is a plant-based mycotoxin that produces HD like symptoms in animals. Oxidative stress and nitric oxide mechanisms have been recently proposed in the 3-NP-induced neurotoxicity. Epigallocatechin gallate (EGCG) is one of the major components of green tea, known for its potent antioxidant activity. Besides, neuroprotective effect of EGCG has also been suggested in different experimental models.
The present study has been designed to examine possible effect of EGCG against 3-NP induced behavioral, oxidative stress, mitochondrial dysfunction, and striatal damage in rats and its possible interaction with nitric oxide modulators.
Systemic 3-NP (10 mg/kg) administration for 14 days significantly reduced locomotor activity, body weight, grip strength, oxidative defense (raised levels of lipid peroxidation, nitrite concentration, depletion of antioxidant enzyme), and mitochondrial enzymes activity in striatum, cortex, and hippocampal regions of the brain.
Fourteen days of EGCG pretreatment (10, 20, and 40 mg/kg) significantly attenuated behavioral alterations, oxidative damage, mitochondrial complex enzymes dysfunction, and striatal damage in 3-NP-treated animals. L-arginine (50 mg/kg) pretreatment with sub-effective dose of EGCG (20 mg/kg) significantly reversed the protective behavioral, biochemical, cellular, and histological effects of EGCG. However, L-NAME (10 mg/kg) pretreatment with EGCG (20 mg/kg) significantly potentiated the protective effect of EGCG which was significant as compared to their effect per se.
The present study shows that EGCG attenuate 3-NP-induced neurotoxicity, and nitric oxide modulation might be involved in its protective action.
氧化应激在神经退行性疾病中起着重要作用。3-硝基丙酸（3-NP）是一种植物源真菌毒素，能在动物中产生类似亨廷顿病的症状。氧化应激和一氧化氮机制最近被提出是 3-NP 诱导的神经毒性的原因。表没食子儿茶素没食子酸酯（EGCG）是绿茶的主要成分之一，具有很强的抗氧化活性。此外，EGCG 在不同的实验模型中也表现出神经保护作用。
本研究旨在探讨 EGCG 对 3-NP 诱导的大鼠行为、氧化应激、线粒体功能障碍和纹状体损伤的可能作用及其与一氧化氮调节剂的可能相互作用。
连续 14 天系统给予 3-NP（10mg/kg）显著降低了运动活性、体重、握力、氧化防御（升高的脂质过氧化水平、亚硝酸盐浓度、抗氧化酶耗竭）和纹状体、皮质和海马脑区的线粒体酶活性。
14 天的 EGCG 预处理（10、20 和 40mg/kg）显著减轻了 3-NP 处理动物的行为改变、氧化损伤、线粒体复合酶功能障碍和纹状体损伤。L-精氨酸（50mg/kg）预处理亚有效剂量的 EGCG（20mg/kg）显著逆转了 EGCG 的保护行为、生化、细胞和组织学作用。然而，L-NAME（10mg/kg）预处理与 EGCG（20mg/kg）联合使用显著增强了 EGCG 的保护作用，与它们各自的作用相比更为显著。
本研究表明，EGCG 减轻了 3-NP 诱导的神经毒性，一氧化氮调节可能参与其保护作用。
