Molecular Drug Metabolism and Toxicology Unit, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Molecular Drug Metabolism and Toxicology Unit, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Biochem Biophys Res Commun. 2018 Sep 5;503(2):1042-1048. doi: 10.1016/j.bbrc.2018.06.114. Epub 2018 Jun 27.
1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) is a neurotoxin that causes Parkinson's disease in animals via mechanisms linked with oxidative stress and inflammation. Resveratrol is a natural polyphenol and a phytoalexin with antioxidative and antiinflammatory properties. Here, we investigated the rescue role of resveratrol on MPTP-triggered toxicity in Drosophila melanogaster for the first time. D. melanogaster (Harwich strain, 1-to 3- days old) were first orally exposed to resveratrol (0, 7.5, 15, 30, 60 and 120 mg/kg diet) and MPTP (0, 250, 500, 1000, 2000, and 3000 μM) for longevity and 7 days survival assays respectively. Consequently, we selected resveratrol (30 and 60 mg/kg diet) to evaluate its rescue role on MPTP (250 and 500 μM)-induced toxicity in D. melanogaster after 3 days of oral treatment. Specifically, we evaluated markers of neurotoxicity (acetylcholinesterase and negative geotaxis), inflammation (nitric oxide), oxidative stress-antioxidant status (hydrogen peroxide, total thiol, catalase and glutathione-S-transferase), cell viability and fecundity. The data showed that resveratrol increased lifespan of D. melanogaster in a dose-dependent manner up to 60 mg/kg diet. Further, resveratrol restored MPTP-induced inhibition of catalase, glutathione-S-transferase and acetylcholinesterase activities in D. melanogaster. Moreover, resveratrol ameliorated MPTP-triggered cell death, histological alterations, behavioural deficits and accumulation of nitric oxide and hydrogen peroxide levels in flies (p < 0.05). Conclusively, the lifespan extension effects of resveratrol and its rescue role on MPTP- mediated toxicity in the flies may be due to its antioxidant and anti-inflammatory properties.
1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）是一种神经毒素，通过与氧化应激和炎症相关的机制在动物中引起帕金森病。白藜芦醇是一种天然多酚和植物抗毒素，具有抗氧化和抗炎特性。在这里，我们首次研究了白藜芦醇对果蝇中 MPTP 触发毒性的挽救作用。D. melanogaster（Harwich 品系，1-3 天大）首先经口暴露于白藜芦醇（0、7.5、15、30、60 和 120 mg/kg 饮食）和 MPTP（0、250、500、1000、2000 和 3000 μM），分别进行寿命和 7 天生存试验。因此，我们选择白藜芦醇（30 和 60 mg/kg 饮食）来评估其对 MPTP（250 和 500 μM）诱导的果蝇毒性的挽救作用，口服治疗 3 天后。具体来说，我们评估了神经毒性标志物（乙酰胆碱酯酶和负向趋地性）、炎症标志物（一氧化氮）、氧化应激-抗氧化状态标志物（过氧化氢、总巯基、过氧化氢酶和谷胱甘肽-S-转移酶）、细胞活力和繁殖力。结果表明，白藜芦醇以剂量依赖的方式增加了果蝇的寿命，最高可达 60 mg/kg 饮食。此外，白藜芦醇恢复了 MPTP 诱导的果蝇过氧化氢酶、谷胱甘肽-S-转移酶和乙酰胆碱酯酶活性的抑制。此外，白藜芦醇改善了 MPTP 触发的果蝇细胞死亡、组织学改变、行为缺陷以及一氧化氮和过氧化氢水平的积累（p<0.05）。总之，白藜芦醇的延长寿命作用及其对果蝇中 MPTP 介导毒性的挽救作用可能与其抗氧化和抗炎特性有关。
