Kheradmand Afshin, Nayebi Alireza Mohajjel, Jorjani Masoumeh, Haddadi Rasool
Drug Applied Research Center, Department of Pharmacology and Toxicology, Tabriz University of Medical Sciences, Tabriz, Iran.
Drug Applied Research Center, Department of Pharmacology and Toxicology, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Iran J Basic Med Sci. 2016 May;19(5):490-6.
Neuroinflammation and oxidative stress play a key role in pathogenesis of Parkinson's disease (PD). In the present study we investigated the effect of reactive oxygen species (ROS) scavenger WR-1065 on catalepsy and cerebrospinal fluid (CSF) level of interleukin 6(IL-6) and striatum superoxide dismutase (SOD) activity in 6-hydroxydopamine (6-OHDA) induced experimental model of PD.
Seventy two male Wistar rats were divided into 9 equal groups and 6-OHDA (8 μg/2 μl/rat) was infused unilaterally into substantia nigra pars copmacta (SNc) to induce PD. Catalepsy was measured by standard bar test, CSF level of IL-6 was assessed by enzyme-linked immunosorbent assay (ELISA) method and SOD activity measured by spectrophotometric method. In pre-treatment groups WR-1065 (20, 40 and 80 μg/2 μl/rat/day, for 3 days) was infused into the SNc before 6-OHDA administration and 21 days later, as a recovery period, behavioral and molecular assay tests were done.
Our results showed that pre-treatment with WR-1065 improved (P<0.001) 6-OHDA-induced catalepsy in a dose dependent manner. In 6-OHDA-lesioned animals SOD activity in SNc and CSF level of IL-6 was decreased markedly (P<0.001) when compared with non-lesioned group, while pre-treatment with WR-1065(P<0.001) restored their levels up to the normal range.
Our study indicated that pre-treatment with WR-1065 could modulate catalepsy and IL-6 level in 6-OHDA-lesioned rats. Also WR1065 could increase SOD activity up to normal range. It can be regarded as an anti-oxidative drug in prevention or adjunctive therapy of PD.
神经炎症和氧化应激在帕金森病(PD)的发病机制中起关键作用。在本研究中,我们研究了活性氧(ROS)清除剂WR - 1065对6 - 羟基多巴胺(6 - OHDA)诱导的PD实验模型中僵住症、脑脊液(CSF)白细胞介素6(IL - 6)水平及纹状体超氧化物歧化酶(SOD)活性的影响。
72只雄性Wistar大鼠被分为9个相等的组,将6 - OHDA(8μg/2μl/只大鼠)单侧注入黑质致密部(SNc)以诱导PD。通过标准杆试验测量僵住症,采用酶联免疫吸附测定(ELISA)法评估CSF中IL - 6水平,并用分光光度法测量SOD活性。在预处理组中,在给予6 - OHDA之前将WR - 1065(20、40和80μg/2μl/只大鼠/天,共3天)注入SNc,21天后,作为恢复期,进行行为和分子分析测试。
我们的结果表明,WR - 1065预处理以剂量依赖性方式改善了(P<0.001)6 - OHDA诱导的僵住症。与未损伤组相比,6 - OHDA损伤动物的SNc中SOD活性和CSF中IL - 6水平显著降低(P<0.001),而WR - 1065预处理(P<0.001)将它们的水平恢复到正常范围。
我们的研究表明,WR - 1065预处理可调节6 - OHDA损伤大鼠的僵住症和IL - 6水平。此外,WR1065可将SOD活性提高到正常范围。它可被视为预防或辅助治疗PD的抗氧化药物。