School of Veterinary and Biomedical Sciences, James Cook University, Australia.
J Toxicol Sci. 2013 Feb;38(1):25-33. doi: 10.2131/jts.38.25.
The catecholaminergic neurotoxin 6-hydroxydopamine is used to lesion dopaminergic pathways in the experimental animal models of Parkinson's disease. The present study was aimed to evaluate the combined treatment with bioflavonoid quercetin (QN) and desferrioxamine (DFO) on 6-hydroxydopamine (6-OHDA) - induced neurotoxicity in the striatum of rats. Adult, male Sprague - Dawley rats were divided into control, sham lesion, 6-OHDA treated (300 µg, intracisternal), 6-OHDA with QN (50 mg/kg) treated, 6-OHDA with DFO (50 mg/kg) treated and 6-OHDA with QN and DFO treated groups. Striatal dopamine, protein carbonyl content (PCC), glutathione (GSH) and superoxide dismutase (SOD) were estimated. There was a significant increase (p < 0.05) in PCC and decrease in dopamine, GSH and SOD level and striatal neuronal number with 6-OHDA treatment. QN and DFO treatment significantly (p < 0.05) reduced these changes showing a significant neuronal protection. Combined treatment has a more significant effect (p < 0.05) in protecting the neurons and increasing the antioxidant enzymes in the striatum. In conclusion, an antioxidant with iron chelator treatment showed a significant neuroprotective effect against 6-hydroxydopamine (6-OHDA) by preventing dopaminergic neuronal loss and maintaining the striatal dopamine level.
儿茶酚胺神经毒素 6-羟多巴胺被用于帕金森病实验动物模型中多巴胺能通路的损伤。本研究旨在评估生物类黄酮槲皮素(QN)和去铁胺(DFO)联合治疗对大鼠纹状体中 6-羟多巴胺(6-OHDA)诱导的神经毒性的作用。成年雄性 Sprague-Dawley 大鼠分为对照组、假损伤组、6-OHDA 处理组(300μg,脑室内)、6-OHDA 与 QN(50mg/kg)处理组、6-OHDA 与 DFO(50mg/kg)处理组和 6-OHDA 与 QN 和 DFO 处理组。测定纹状体多巴胺、蛋白羰基含量(PCC)、谷胱甘肽(GSH)和超氧化物歧化酶(SOD)。用 6-OHDA 处理后,PCC 显著增加(p<0.05),多巴胺、GSH 和 SOD 水平以及纹状体神经元数量减少。QN 和 DFO 治疗显著(p<0.05)降低了这些变化,显示出显著的神经元保护作用。联合治疗对保护神经元和增加纹状体抗氧化酶具有更显著的效果(p<0.05)。总之,抗氧化剂与铁螯合剂联合治疗通过防止多巴胺能神经元丢失和维持纹状体多巴胺水平,对 6-羟多巴胺(6-OHDA)表现出显著的神经保护作用。