title: Are delta-aminolevulinate dehydratase inhibition and metal concentrations additional factors for the age-related cognitive decline?
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.
authors.affiliation: Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil. mariliabaierle@yahoo.com.br.
authors.forename: Marília
authors.initials: M
authors.lastname: Baierle
authors.affiliation: Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil. marifeiffercharao@yahoo.com.br.
authors.forename: Mariele F
authors.initials: MF
authors.lastname: Charão
authors.affiliation: Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil. goethel_63@hotmail.com.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Göethel
authors.affiliation: Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil. anebarth.88@gmail.com.
authors.forename: Anelise
authors.initials: A
authors.lastname: Barth
authors.affiliation: Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil. rafael.fra@hotmail.com.
authors.forename: Rafael
authors.initials: R
authors.lastname: Fracasso
authors.affiliation: Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil. bubols@hotmail.com.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Bubols
authors.affiliation: Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil. elisa-sauer@hotmail.com.
authors.forename: Elisa
authors.initials: E
authors.lastname: Sauer
authors.affiliation: Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil. sarah_chagass@yahoo.com.br.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Campanharo
authors.affiliation: Department of Chemistry, Pontifical Catholic University of Rio de Janeiro (PUC-Rio), Rio de Janeiro, RJ 22451-900, Brazil. rafaelccr@puc-rio.br.
authors.forename: Rafael C C
authors.initials: RC
authors.lastname: Rocha
authors.affiliation: Department of Chemistry, Pontifical Catholic University of Rio de Janeiro (PUC-Rio), Rio de Janeiro, RJ 22451-900, Brazil. tatispierre@puc-rio.br.
authors.forename: Tatiana D
authors.initials: TD
authors.lastname: Saint'Pierre
authors.affiliation: Institute of Psychology, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90035-003, Brazil. su.suelen@gmail.com.
authors.forename: Suelen
authors.initials: S
authors.lastname: Bordignon
authors.affiliation: Institute of Psychology, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90035-003, Brazil. mugazibetti@gmail.com.
authors.forename: Murilo
authors.initials: M
authors.lastname: Zibetti
authors.affiliation: Institute of Psychology, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS 90035-003, Brazil. clarissatrentini@terra.com.br.
authors.forename: Clarissa M
authors.initials: CM
authors.lastname: Trentini
authors.affiliation: Post-graduate Program of Biochemistry, Federal University of Pampa, Uruguaiana, RS 97500-970, Brazil. avilads1@gmail.com.
authors.forename: Daiana S
authors.initials: DS
authors.lastname: Avila
authors.affiliation: Department of Chemistry, Pontifical Catholic University of Rio de Janeiro (PUC-Rio), Rio de Janeiro, RJ 22451-900, Brazil. agioda@puc-rio.br.
authors.forename: Adriana
authors.initials: A
authors.lastname: Gioda
authors.affiliation: Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil. solange.garcia@ufrgs.br.
authors.forename: Solange C
authors.initials: SC
authors.lastname: Garcia
mesh_terms: D000328:Adult; D000368:Aged; D001938:Brazil / Q000453:epidemiology; D003071:Cognition; D003072:Cognition Disorders / Q000097:blood / Q000201:enzymology / Q000453:epidemiology*; D004791:Enzyme Inhibitors / Q000097:blood / Q000633:toxicity*; D005260:Female; D006801:Humans; D008297:Male; D019216:Metals, Heavy / Q000097:blood* / Q000633:toxicity; D008875:Middle Aged; D018384:Oxidative Stress; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors / Q000097:blood*; D012643:Selenium / Q000172:deficiency
chemical_list: D004791:Enzyme Inhibitors; D019216:Metals, Heavy; D000623:Porphobilinogen Synthase; D012643:Selenium