Lead (Pb), a ubiquitous heavy metal and a known neurotoxicant, produces adverse effects on the brain via increased production of reactive oxygen species (ROS) and causes oxidative stress. In this study we examined the neuroprotective effects of the ethanolic extract of Nigella sativa L. seeds on Pb induced oxidative stress in the developing brain of mice. Mouse pups were exposed to low (0.1%) and high (0.2%) doses of Pb from the first day of pregnancy through their mothers (via drinking water) and lactation until post-natal day (PND) 21. The mRNA expression levels of superoxide dismutase (SOD1), peroxiredoxin (Prdx6), amyloid precursor protein (APP) common, APP695 and APP770 were examined in the cortex and hippocampus of the mouse brain excised on PND 21 by semi-quantitative RT-PCR. The free radical scavenging activity of ethanolic Nigella sativa L. extract was assessed by DPPH assay. The results showed that Pb exposure caused a significant decrease in the expression of SOD1, Prdx6 and APP695 and an increase in APP770 in both cortex and hippocampus in a dose dependent manner as compared to the control group. The expression of APP common remained unaltered. Histological assessment of the cortex and hippocampus demonstrated a decrease in the neuronal number and Nissl bodies. The administration of 250 and 500 mg kg⁻¹ ethanolic Nigella sativa L. extract reversed the adverse effects by significantly increasing the expression of SOD1, Prdx6 and APP695 and decreasing the expression of APP770 in both the regions. These results strongly suggest that Nigella sativa L. supplementation greatly improves Pb-induced neurotoxicity in early life and provides neuroprotective and antioxidant potentials.

中文翻译：

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Nigella sativa L.种子提取物对小鼠模型发育和早期生命中铅诱导的神经毒性的 保护作用†

铅（Pb）是一种普遍存在的重金属，是一种已知的神经毒性物质，它通过增加活性氧（ROS）的产生而对大脑产生不利影响，并引起氧化应激。在这项研究中，我们研究了Nigella sativa L.种子的乙醇提取物对铅诱导的小鼠大脑中氧化应激的神经保护作用。小鼠幼仔暴露于低（0.1％）和高（0.2％），从通过其母亲在怀孕的第一天剂量的Pb（经由直到产后一天（PND）为止都应进行泌乳。21.检查了大鼠皮层和海马中的超氧化物歧化酶（SOD1），过氧化物酶（Prdx6），淀粉样前体蛋白（APP），APP695和APP770的mRNA表达水平。半定量RT-PCR在PND 21上切除小鼠大脑。乙醇Nigella sativa L.的自由基清除活性。提取物通过DPPH分析评估。结果表明，与对照组相比，铅暴露导致皮质和海马中SOD1，Prdx6和APP695的表达显着降低，而APP770的表达呈剂量依赖性。APP共同表达仍未改变。皮层和海马的组织学评估显示神经元数量和尼氏体减少。施用250和500 mg kg ^-1的乙醇Nigella sativa L.提取物可通过显着增加两个区域中SOD1，Prdx6和APP695的表达并降低APP770的表达来逆转不良反应。这些结果有力地证明了Nigella sativa L.。 补充可大大改善铅在早期生命中引起的神经毒性，并具有神经保护和抗氧化的潜力。