Ozsoy O, Yildirim F B, Ogut E, Kaya Y, Tanriover G, Parlak H, Agar A, Aslan M
Department of Physiology, Faculty of Medicine, Akdeniz University , Antalya , Turkey.
Free Radic Res. 2015;49(8):1004-14. doi: 10.3109/10715762.2015.1027198. Epub 2015 Apr 25.
Melatonin is known to reduce detrimental effects of free radicals by stimulating antioxidant enzymes; however, its role has not been studied in 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease (PD). Therefore, we aimed to elucidate the effects of melatonin on motor activity and oxidative stress parameters in 6-OHDA-induced rat model of PD. Three-month-old male Wistar rats were divided into 5 groups: vehicle (V), melatonin-treated (M), 6-OHDA-injected (6-OHDA), 6-OHDA-injected + melatonin-treated (6-OHDA-Mel), and melatonin-treated + 6-OHDA-injected (Mel-6-OHDA) group. Melatonin was administered intraperitoneally at a dose of 10 mg/kg/day for 30 days in M and Mel-6-OHDA groups, for 7 days in 6-OHDA-Mel group. Rats received a unilateral stereotaxic injection of 6-OHDA into the right medial forebrain bundle. The 6-OHDA-Mel group started receiving melatonin when experimental PD was created and the treatment was continued for 7 days. In the Mel-6-OHDA group, experimental PD was created on the 23rd day of melatonin treatment and continued for the remaining 7 days. Locomotor activity decreased in 6-OHDA group compared with that in vehicle group; however, melatonin treatment did not improve this impairment. 6-OHDA injection caused an obvious reduction in tyrosine-hydroxylase-positive dopaminergic neuron viability as determined by immunohistochemistry. Melatonin supplementation decreased dopaminergic neuron death in 6-OHDA-Mel and Mel-6-OHDA groups compared with that in 6-OHDA group. Biochemical analysis confirmed the beneficial effects of melatonin displaying higher superoxide dismutase, catalase, and glutathione peroxidase activities and lower lipid peroxidation in substantia nigra samples in comparison to non-treated 6-OHDA group. Starting melatonin treatment before creating experimental PD was more effective on observed changes.
已知褪黑素可通过刺激抗氧化酶来减少自由基的有害影响；然而，其在6-羟基多巴胺（6-OHDA）诱导的帕金森病（PD）大鼠模型中的作用尚未得到研究。因此，我们旨在阐明褪黑素对6-OHDA诱导的PD大鼠模型运动活性和氧化应激参数的影响。将3个月大的雄性Wistar大鼠分为5组：溶剂对照组（V）、褪黑素治疗组（M）、6-OHDA注射组（6-OHDA）、6-OHDA注射+褪黑素治疗组（6-OHDA-Mel）和褪黑素治疗+6-OHDA注射组（Mel-6-OHDA）。M组和Mel-6-OHDA组以10 mg/kg/天的剂量腹腔注射褪黑素，持续30天；6-OHDA-Mel组持续7天。大鼠接受右侧内侧前脑束的单侧立体定向注射6-OHDA。6-OHDA-Mel组在建立实验性PD时开始接受褪黑素治疗，并持续治疗7天。在Mel-6-OHDA组中，在褪黑素治疗的第23天建立实验性PD，并持续7天。与溶剂对照组相比，6-OHDA组的运动活性降低；然而，褪黑素治疗并未改善这种损伤。通过免疫组织化学测定，6-OHDA注射导致酪氨酸羟化酶阳性多巴胺能神经元活力明显降低。与6-OHDA组相比，补充褪黑素可降低6-OHDA-Mel组和Mel-6-OHDA组的多巴胺能神经元死亡。生化分析证实了褪黑素的有益作用，与未治疗的6-OHDA组相比，黑质样本中的超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活性更高，脂质过氧化更低。在建立实验性PD之前开始褪黑素治疗对观察到的变化更有效。
