Abstract

Parkinson’s disease (PD) is the second most prevalent progressive neurodegenerative disease, characterized by loss of dopaminergic neurons in substantia nigra, with deficiency of dopamine in the striatum. Tramadol is safe analgesic but long-term use confirmed to elevate oxidative stress, neuroinflammation, mitochondrial dysfunction, in brain leads to motor deficits. l-Theanine is an active constituent of green tea which prevents neuronal loss, mitochondrial failure and improves dopamine, gamma-aminobutyric acid (GABA), serotonin levels and in the central nervous system (CNS) via antioxidant, anti-inflammatory, and neuromodulatory properties. In the present study, tramadol was injected intraperitoneally to Wister rats for 28 days at a dose of 50 mg/kg. l-Theanine (25, 50, and 100 mg/kg) was administered orally 3 h before tramadol administration from day 14 to day 28. Behavioral analyses including rotarod, narrow beam walk, open field, and grip strength were used to evaluate motor coordination on a weekly basis. On the day 29, all Wistar rats were sacrificed and striatum homogenates were used for biochemical (lipid peroxidation, nitrite, glutathione, glutathione peroxidase activity, superoxide dismutase, catalase, mitochondrial complex I, IV, and cyclic adenosine monophosphate), neuroinflammatory markers (tumor necrosis factor-α, interleukin-1β, and interleukin-17), and neurotransmitters (dopamine, norepinephrine, serotonin, GABA, and glutamate) analysis. Chronic tramadol treatment caused motor deficits reduced antioxidant enzymes level, increased striatal proinflammatory cytokines release, dysbalanced neurotransmitters, and reduced mitochondrial complex activity I, IV, and cAMP activity. However, l-theanine administration attenuated behavioral, biochemical, neuroinflammatory, neurotransmitters, and mitochondrial activity indicated it as a promising neuroprotective potential against degenerative changes in experimental model of PD.

摘要

帕金森病 (PD) 是第二大流行的进行性神经退行性疾病，其特征是黑质中多巴胺能神经元的丧失，纹状体中的多巴胺缺乏。曲马多是安全的镇痛剂，但长期使用证实会增加大脑中的氧化应激、神经炎症、线粒体功能障碍，导致运动障碍。l-茶氨酸是绿茶中的一种活性成分，可通过抗氧化、抗炎和神经调节特性防止神经元丢失、线粒体衰竭并改善多巴胺、γ-氨基丁酸 (GABA)、血清素水平和中枢神经系统 (CNS) . 在本研究中，曲马多以 50 mg/kg 的剂量向 Wister 大鼠腹膜内注射 28 天。l-从第 14 天到第 28 天，在曲马多给药前 3 小时口服茶氨酸（25、50 和 100 mg/kg）。行为分析包括旋转杆、窄束行走、开阔场地和握力来评估运动协调性每周一次。在第 29 天，处死所有 Wistar 大鼠，纹状体匀浆用于生化（脂质过氧化、亚硝酸盐、谷胱甘肽、谷胱甘肽过氧化物酶活性、超氧化物歧化酶、过氧化氢酶、线粒体复合物 I、IV 和环磷酸腺苷）、神经炎症标志物（肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-17）和神经递质（多巴胺、去甲肾上腺素、血清素、GABA和谷氨酸）分析。慢性曲马多治疗导致运动障碍降低抗氧化酶水平，增加纹状体促炎细胞因子释放，神经递质失衡，线粒体复合物活性 I、IV 和 cAMP 活性降低。然而，l-茶氨酸给药减弱了行为、生化、神经炎症、神经递质和线粒体活性，表明它在 PD 实验模型中具有对抗退行性变化的有希望的神经保护潜力。