Venkareddy Lalith Kumar
Department of Biochemistry and Nutrition, CSIR-Central Food Technological Research Institute (CFTRI), Mysore 570020, India.
Department of Biochemistry and Nutrition, CSIR-Central Food Technological Research Institute (CFTRI), Mysore 570020, India.
Neurotoxicology. 2015 May;48:142-51. doi: 10.1016/j.neuro.2015.03.014. Epub 2015 Apr 3.
Understanding the interaction between dietary protein deficits and neurotoxicants such as lead (Pb) is critical since oxidative stress is a common denominator under such conditions. The Drosophila system is an extensively used model to investigate the interaction between nutrients and environmental toxicants. Accordingly, we have examined the hypothesis that casein (CSN) enrichment has the propensity to attenuate Pb-associated phenotype, oxidative stress and neurotoxicity in Drosophila melanogaster. Exposure of young (2-3 d) and adult flies (10-12 d old) to Pb acetate (0-20 mM, 7 d) in the medium resulted in a concentration dependent mortality and the survivors exhibited a hyperactive phenotype. While males showed higher susceptibility to Pb among both age groups, young flies were relatively more susceptible than adults. Pb exposure (5-10 mM, 5 d) among young flies caused robust oxidative stress as evidenced by markedly elevated levels of reactive oxygen species with concomitant perturbations in the activities of antioxidant enzymes (diminished SOD and elevated thioredoxin reductase) and altered redox state. Further, Pb caused significant elevation in the activity of acetylcholinesterase and dopamine levels. In a satellite study, we assessed the modulatory effect of CSN-enriched diet (1-2%) on Pb intoxication in terms of lethality, hyperactivity, oxidative stress and neurotoxicity. CSN markedly offset Pb-induced lethality and diminished the hyperactivity response. While CSN enrichment among Pb (5 mM) treated flies caused further elevation in ROS levels and thioredoxin reductase activity, the SOD levels were restored to normalcy. Further, CSN improved the activity levels of complex I-III and restored the dopamine levels. Our data suggest that Pb-induced toxicity in the Drosophila system may be predominantly mediated through oxidative stress mechanisms and the propensity of casein-enriched diet to abrogate such responses. Hence, we propose that enrichment of diet with protein such as casein may be a useful approach to alleviate Pb associated adverse effects in children.
了解膳食蛋白质缺乏与铅（Pb）等神经毒物之间的相互作用至关重要，因为氧化应激是这些情况下的一个共同因素。果蝇系统是研究营养物质与环境毒物相互作用的广泛使用的模型。因此，我们检验了以下假设：酪蛋白（CSN）富集有减轻黑腹果蝇中铅相关表型、氧化应激和神经毒性的倾向。在培养基中让年轻果蝇（2 - 3天龄）和成年果蝇（10 - 12天龄）暴露于醋酸铅（0 - 20 mM，7天）会导致浓度依赖性死亡率，幸存者表现出多动表型。虽然在两个年龄组中雄性对铅更敏感，但年轻果蝇比成年果蝇相对更敏感。在年轻果蝇中暴露于铅（5 - 10 mM，5天）会导致强烈的氧化应激，表现为活性氧水平显著升高，同时抗氧化酶活性受到干扰（超氧化物歧化酶减少，硫氧还蛋白还原酶升高）以及氧化还原状态改变。此外，铅导致乙酰胆碱酯酶活性和多巴胺水平显著升高。在一项附属研究中，我们评估了富含CSN的饮食（1 - 2%）对铅中毒在致死率、多动、氧化应激和神经毒性方面的调节作用。CSN显著抵消了铅诱导的致死率并减轻了多动反应。虽然在经铅（5 mM）处理的果蝇中CSN富集导致活性氧水平和硫氧还蛋白还原酶活性进一步升高，但超氧化物歧化酶水平恢复到正常。此外，CSN改善了复合物I - III的活性水平并恢复了多巴胺水平。我们的数据表明，果蝇系统中铅诱导的毒性可能主要通过氧化应激机制介导，以及富含酪蛋白的饮食消除此类反应的倾向。因此，我们提出用酪蛋白等蛋白质丰富饮食可能是减轻儿童铅相关不良反应的一种有用方法。
