Adedara Isaac A, Abolaji Amos O, Rocha Joao B T, Farombi Ebenezer O
Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Departamento de Bioquímica e Biologia Molecular, CCNE, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil.
Neurochem Res. 2016 Jun;41(6):1430-8. doi: 10.1007/s11064-016-1852-x. Epub 2016 Feb 15.
Several experimental and epidemiological reports have associated manganese exposure with induction of oxidative stress and locomotor dysfunctions. Diphenyl diselenide (DPDS) is widely reported to exhibit antioxidant, anti-inflammatory and neuroprotective effects in in vitro and in vivo studies via multiple biochemical mechanisms. The present study investigated the protective effect of DPDS on manganese-induced toxicity in Drosophila melanogaster. The flies were exposed, in a dietary regimen, to manganese alone (30 mmol per kg) or in combination with DPDS (10 and 20 µmol per kg) for 7 consecutive days. Exposure to manganese significantly (p < 0.05) increased flies mortality, whereas the survivors exhibited significant locomotor deficits with increased acetylcholinesterase (AChE) activity. However, dietary supplementation with DPDS caused a significant decrease in mortality, improvement in locomotor activity and restoration of AChE activity in manganese-exposed flies. Additionally, the significant decreases in the total thiol level, activities of catalase and glutathione-S-transferase were accompanied with significant increases in the generation of reactive oxygen and nitrogen species and thiobarbituric acid reactive substances in flies exposed to manganese alone. Dietary supplementation with DPDS significantly augmented the antioxidant status and prevented manganese-induced oxidative stress in the treated flies. Collectively, the present data highlight that DPDS may be a promising chemopreventive drug candidate against neurotoxicity resulting from acute manganese exposure.
多项实验和流行病学报告表明，锰暴露与氧化应激诱导及运动功能障碍有关。二苯基二硒醚（DPDS）在体外和体内研究中通过多种生化机制广泛表现出抗氧化、抗炎和神经保护作用。本研究调查了DPDS对果蝇体内锰诱导毒性的保护作用。果蝇通过饮食方案连续7天单独暴露于锰（每千克30毫摩尔）或与DPDS联合暴露（每千克10和20微摩尔）。暴露于锰显著（p<0.05）增加了果蝇死亡率，而存活者表现出显著的运动缺陷，乙酰胆碱酯酶（AChE）活性增加。然而，在饮食中补充DPDS可显著降低锰暴露果蝇的死亡率，改善运动活性并恢复AChE活性。此外，单独暴露于锰的果蝇中，总硫醇水平、过氧化氢酶和谷胱甘肽-S-转移酶活性显著降低，同时活性氧和氮物种以及硫代巴比妥酸反应性物质的生成显著增加。在饮食中补充DPDS可显著增强处理后果蝇的抗氧化状态并预防锰诱导的氧化应激。总体而言，目前的数据表明DPDS可能是一种有前景的化学预防药物候选物，可对抗急性锰暴露导致的神经毒性。
