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δ-氨基乙酰丙酸脱水酶抑制和金属浓度是与年龄相关的认知衰退的额外因素吗?

Are delta-aminolevulinate dehydratase inhibition and metal concentrations additional factors for the age-related cognitive decline?

作者信息

Baierle Marília, Charão Mariele F, Göethel Gabriela, Barth Anelise, Fracasso Rafael, Bubols Guilherme, Sauer Elisa, Campanharo Sarah C, Rocha Rafael C C, Saint'Pierre Tatiana D, Bordignon Suelen, Zibetti Murilo, Trentini Clarissa M, Avila Daiana S, Gioda Adriana, Garcia Solange C

机构信息

Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil.

Department of Chemistry, Pontifical Catholic University of Rio de Janeiro (PUC-Rio), Rio de Janeiro, RJ 22451-900, Brazil.

出版信息

Int J Environ Res Public Health. 2014 Oct 17;11(10):10851-67. doi: 10.3390/ijerph111010851.

DOI:10.3390/ijerph111010851
PMID:25329536
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4211010/
Abstract

Aging is often accompanied by cognitive impairments and influenced by oxidative status and chemical imbalances. Thus, this study was conducted to examine whether age-related cognitive deficit is associated with oxidative damage, especially with inhibition of the enzyme delta-aminolevulinate dehydratase (ALA-D), as well as to verify the influence of some metals in the enzyme activity and cognitive performance. Blood ALA-D activity, essential (Fe, Zn, Cu, Se) and non-essential metals (Pb, Cd, Hg, As, Cr, Ni, V) were measured in 50 elderly and 20 healthy young subjects. Cognitive function was assessed by tests from Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery and other. The elderly group presented decreased ALA-D activity compared to the young group. The index of ALA-D reactivation was similar to both study groups, but negatively associated with metals. The mean levels of essential metals were within the reference values, while the most toxic metals were above them in both groups. Cognitive function impairments were observed in elderly group and were associated with decreased ALA-D activity, with lower levels of Se and higher levels of toxic metals (Hg and V). Results suggest that the reduced ALA-D activity in elderly can be an additional factor involved in cognitive decline, since its inhibition throughout life could lead to accumulation of the neurotoxic compound ALA. Toxic metals were found to contribute to cognitive decline and also to influence ALA-D reactivation.

摘要

衰老常伴有认知障碍,并受氧化状态和化学失衡的影响。因此,本研究旨在探讨与年龄相关的认知缺陷是否与氧化损伤有关,特别是与δ-氨基乙酰丙酸脱水酶(ALA-D)的抑制有关,同时验证某些金属对该酶活性和认知表现的影响。对50名老年人和20名健康年轻人测量了血液中的ALA-D活性、必需金属(铁、锌、铜、硒)和非必需金属(铅、镉、汞、砷、铬、镍、钒)。通过阿尔茨海默病注册协会(CERAD)成套测试及其他测试评估认知功能。与年轻组相比,老年组的ALA-D活性降低。两个研究组的ALA-D再激活指数相似,但与金属呈负相关。两组中必需金属的平均水平均在参考值范围内,而毒性最大的金属水平均高于参考值。老年组出现认知功能障碍,且与ALA-D活性降低、硒水平降低和毒性金属(汞和钒)水平升高有关。结果表明,老年人ALA-D活性降低可能是认知衰退的另一个相关因素,因为其一生受到抑制可能导致神经毒性化合物ALA的积累。发现毒性金属会导致认知衰退,并影响ALA-D的再激活。

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