铜(Cu)和锌(Zn)需要低浓度的代谢功能,但也有毒。人们非常担心重金属对土壤的污染,这可能会让人们接触到这些有毒物质,通过吸入灰尘或通过摄入来自受污染土壤的食物而暴露于有毒物质。此外,金属组合的毒性是值得怀疑的,因为土壤质量指南只对它们进行单独评估。众所周知,在许多神经退行性疾病的病理影响区域中经常发现金属积累,包括亨廷顿病(HD)。HD是由亨廷顿(HTT)基因中常染色体显性遗传的CAG三核苷酸重复扩增引起的。这导致形成具有异常长的聚谷氨酰胺(polyQ)重复的突变亨廷顿(mHTT)蛋白。HD的病理导致神经元细胞的损失,电机变化,和痴呆症。芦丁是一种在各种食物来源中发现的类黄酮,以前的研究表明,它在HD模型中具有保护作用,并充当金属螯合剂。然而,需要进一步的研究来揭示其对金属代谢不良的影响,并辨别其潜在的机制。在本研究中,我们调查了长期接触铜的毒性效应,锌,和它们的混合物,以及在基于秀丽隐杆线虫的HD模型中与神经毒性和神经变性进展的关系。此外,我们调查了芦丁金属暴露后的影响。总的来说,我们证明长期接触金属和它们的混合物会改变身体参数,运动,和发育迟缓,除了增加肌肉和神经元中的polyQ蛋白聚集体引起神经变性。我们还提出芦丁具有通过涉及抗氧化和螯合性质的机制起作用的保护作用。总之,我们的数据提供了有关金属组合毒性较高的新迹象,芦丁在C.elegansHD模型中的螯合潜力以及未来治疗由与金属相关的蛋白质聚集引起的神经退行性疾病的可能策略。
Copper (Cu) and Zinc (Zn) are required in small concentrations for metabolic functions, but are also toxic. There is a great concern about soil pollution by heavy metals, which may exposure the population to these toxicants, either by inhalation of dust or exposure to toxicants through ingestion of food derived from contaminated soils. In addition, the toxicity of metals in combination is questionable, as soil quality guidelines only assess them separately. It is well known that metal accumulation is often found in the pathologically affected regions of many neurodegenerative diseases, including Huntington\'s disease (HD). HD is caused by an autosomal dominantly inherited CAG trinucleotide repeat expansion in the huntingtin (HTT) gene. This results in the formation of a mutant huntingtin (mHTT) protein with an abnormally long polyglutamine (
polyQ) repeat. The pathology of HD results in loss of neuronal cells, motor changes, and dementia. Rutin is a flavonoid found in various food sources, and previous studies indicate it has protective effects in HD models and acts as a metal chelator. However, further studies are needed to unravel its effects on metal dyshomeostasis and to discern the underlying mechanisms. In the present study, we investigated the toxic effects of long-term exposure to copper, zinc, and their mixture, and the relationship with the progression of neurotoxicity and neurodegeneration in a C. elegans-based HD model. Furthermore, we investigated the effects of rutin post metal exposure. Overall, we demonstrate that chronic exposure to the metals and their mixture altered body parameters, locomotion, and developmental delay, in addition to increasing
polyQ protein aggregates in muscles and neurons causing neurodegeneration. We also propose that rutin has protective effects acting through mechanisms involving antioxidant and chelating properties. Altogether, our data provides new indications about the higher toxicity of metals in combination, the chelating potential of rutin in the C. elegans model of HD and possible strategies for future treatments of neurodegenerative diseases caused by the aggregation of proteins related to metals.