{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T04:44:43Z","timestamp":1762145083732,"version":"build-2065373602"},"reference-count":59,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2014,10,17]],"date-time":"2014-10-17T00:00:00Z","timestamp":1413504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>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\u2019s 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.<\/jats:p>","DOI":"10.3390\/ijerph111010851","type":"journal-article","created":{"date-parts":[[2014,10,17]],"date-time":"2014-10-17T10:27:19Z","timestamp":1413541639000},"page":"10851-10867","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Are Delta-Aminolevulinate Dehydratase Inhibition and Metal Concentrations Additional Factors for the Age-Related Cognitive Decline?"],"prefix":"10.3390","volume":"11","author":[{"given":"Mar\u00edlia","family":"Baierle","sequence":"first","affiliation":[{"name":"Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty,  Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil"},{"name":"Post-graduate Program in Pharmaceutical Sciences (PPGCF), Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariele","family":"Char\u00e3o","sequence":"additional","affiliation":[{"name":"Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty,  Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil"},{"name":"Post-graduate Program in Pharmaceutical Sciences (PPGCF), Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"G\u00f6ethel","sequence":"additional","affiliation":[{"name":"Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty,  Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil"},{"name":"Post-graduate Program in Pharmaceutical Sciences (PPGCF), Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anelise","family":"Barth","sequence":"additional","affiliation":[{"name":"Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty,  Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil"},{"name":"Post-graduate Program in Pharmaceutical Sciences (PPGCF), Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Fracasso","sequence":"additional","affiliation":[{"name":"Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty,  Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil"},{"name":"Post-graduate Program in Pharmaceutical Sciences (PPGCF), Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, 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Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jchromb.2005.04.023","article-title":"Oxidative stress in brain aging, neurodegenerative and vascular diseases: an overview","volume":"827","author":"Mariani","year":"2005","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.neuint.2008.08.011","article-title":"Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: Protective effect of folic acid","volume":"54","author":"Matte","year":"2009","journal-title":"Neurochem. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S75","DOI":"10.1111\/j.1753-4887.2001.tb05505.x","article-title":"Antioxidants and cognitive function","volume":"59","author":"Meydani","year":"2001","journal-title":"Nutr. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Bales, C.W., Ritchie, C.S., and Wellman, N.S. (2009). Handbook of Clinical Nutrition and Aging, Humana Press. [2nd ed.].","DOI":"10.1007\/978-1-60327-385-5"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.archger.2012.11.002","article-title":"Trace elements in the blood of institutionalized elderly in the Czech Republic","volume":"56","author":"Rambouskova","year":"2013","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.ijheh.2011.11.004","article-title":"Gender differences for associations between circulating levels of metals and coronary risk in the elderly","volume":"215","author":"Olsen","year":"2012","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1590\/S0034-89102012000200004","article-title":"Environmental lead poisoning among children in Porto Alegre state, Southern Brazil","volume":"46","author":"Ferron","year":"2012","journal-title":"Rev. Saude Publica"},{"key":"ref_9","first-page":"209","article-title":"Effects of metals on the nervous system of humans and animals","volume":"14","author":"Carpenter","year":"2001","journal-title":"Int. J. Occup. Med. Environ. Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0013-9351(05)80001-5","article-title":"The \u03b4-aminolevulinate dehydratase polymorphism: higher blood lead levels in lead workers and environmentally exposed children with the 1\u20132 and 2\u20132 isozymes","volume":"56","author":"Wetmur","year":"1991","journal-title":"Environ. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.biopha.2007.10.017","article-title":"The influence of the hemodialysis treatment time under oxidative stress biomarkers in chronic renal failure patients","volume":"62","author":"Valentini","year":"2008","journal-title":"Biomed. Pharmacother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1093\/ndt\/gfp001","article-title":"The plasma retinol levels as pro-oxidant\/oxidant agents in haemodialysis patients","volume":"24","author":"Roehrs","year":"2009","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.clinbiochem.2007.02.007","article-title":"Human erythrocyte delta-aminolevulinate dehydratase activity and oxidative stress in hemodialysis patients","volume":"40","author":"Valentini","year":"2007","journal-title":"Clin. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1039\/c2tx20014g","article-title":"Aminolevulinate dehydratase (d-ALA-D) as marker protein of intoxication with metals and other pro-oxidant situations","volume":"1","author":"Rocha","year":"2012","journal-title":"Toxicol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1590\/S1676-24442010000600006","article-title":"Poss\u00edveis efeitos do cobre sangu\u00edneo sobre par\u00e2metros hematol\u00f3gicos em idosas","volume":"46","author":"Baierle","year":"2010","journal-title":"J. Bras. Patol. Med. Lab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1159\/000459097","article-title":"Delta-aminolevulinic acid dehydratase assay","volume":"28","author":"Sassa","year":"1982","journal-title":"Enzyme"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.sab.2013.03.003","article-title":"Study of the chemical composition of particulate matter from the Rio de Janeiro metropolitan region, Brazil, by inductively coupled plasma-mass spectrometry and optical emission spectrometry","volume":"86","author":"Mateus","year":"2013","journal-title":"Spect. Acta B Atomic Spect."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1590\/S0004-282X2001000400009","article-title":"Applicability of the CERAD neuropsychological battery to Brazilian elderly","volume":"59","author":"Bertolucci","year":"2001","journal-title":"Arquivos de Neuro-Psiquiatria."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"\u201cMini-mental state\u201d. A practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J. Psychiatr. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1590\/S0004-282X2003000500014","article-title":"Sugest\u00f5es para o uso do Mini-Exame do Estado Mental no Brasil","volume":"61","author":"Brucki","year":"2003","journal-title":"Arquivos de Neuro-Psiquiatria."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wechsler, D. (1997). Weschsler Adult Intelligence Scale-III, The Psychological Corporation.","DOI":"10.1037\/t49755-000"},{"key":"ref_22","unstructured":"Nascimento, E. (2005). Wais-III: Escala de Intelig\u00eancia Wechsler para Adultos\u2014Manual T\u00e9cnico, Casa do Psic\u00f3logo."},{"key":"ref_23","unstructured":"Hoffman, R., Benz, E.J., Shattil, S.J., Furie, B., and Silberstein, L.E. (2009). Hematology Basic Principles and Practice, Churchill Livingstone Elsevier. [5th ed.]."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1590\/S0034-71672012000300013","article-title":"Perfil epidemiol\u00f3gico, cl\u00ednico e de independ\u00eancia funcional de uma popula\u00e7\u00e3o idosa institucionalizada","volume":"65","author":"Lisboa","year":"2012","journal-title":"Rev. Bras. Enferm."},{"key":"ref_25","unstructured":"World Health Organization (WHO) (1996). Trace Elements in Human Nutrition and Health, WHO."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1590\/S1809-98232011000100012","article-title":"Decl\u00ednio cognitivo de idosos e sua associa\u00e7\u00e3o com fatores epidemiol\u00f3gicos em Vi\u00e7osa, Minas Gerais","volume":"14","author":"Machado","year":"2011","journal-title":"Rev. Bras. Geriatr. Gerontol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1590\/S0103-166X2012000200001","article-title":"Qualidade de vida, cogni\u00e7\u00e3o e desempenho nas fun\u00e7\u00f5es executivas de idosos","volume":"29","author":"Beckert","year":"2012","journal-title":"Estudos de Psicologia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"306","DOI":"10.3109\/01480545.2012.720989","article-title":"Evaluation of lipid damage related to pathological and physiological conditions","volume":"36","author":"Garcia","year":"2013","journal-title":"Drug Chem. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/j.clinbiochem.2007.08.013","article-title":"The influence of the serum vitamin C levels on oxidative stress biomarkers in elderly women","volume":"40","author":"Paniz","year":"2007","journal-title":"Clin. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.cca.2007.04.024","article-title":"Low level lead exposure and oxidative stress: Current opinions","volume":"383","author":"Ahamed","year":"2007","journal-title":"Clin. Chim. Acta"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"38","DOI":"10.5582\/bst.2011.v5.1.38","article-title":"Environmental lead exposure as a risk for childhood aplastic anemia","volume":"5","author":"Ahamed","year":"2011","journal-title":"Biosci. Trends"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-079X.1998.tb00359.x","article-title":"In vivo protection by melatonin against delta-aminolevulinic acid-induced oxidative damage and its antioxidant effect on the activity of haem enzymes","volume":"24","author":"Princ","year":"1998","journal-title":"J. Pineal Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/0891-5849(95)02035-7","article-title":"The prooxidant effect of 5-aminolevulinic acid in the brain tissue of rats: Implications in neuropsychiatric manifestations in porphyrias","volume":"20","author":"Demasi","year":"1996","journal-title":"Free Radic. Biol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.ntt.2009.08.003","article-title":"Lead and cognitive function in ALAD genotypes in the third National Health and Nutrition Examination Survey","volume":"31","author":"Krieg","year":"2009","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1136\/oem.2006.027417","article-title":"Delta-aminolevulinic acid dehydratase polymorphism and the relation between low level lead exposure and the Mini-Mental Status Examination in older men: The Normative Aging Study","volume":"63","author":"Weuve","year":"2006","journal-title":"Occup. Environ. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/BF00235687","article-title":"Delta-Aminolaevulinic acid and amino acid neurotransmitters","volume":"38","author":"Brennan","year":"1981","journal-title":"Mol. Cell. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/0306-3623(84)90215-5","article-title":"The effect of delta-aminolaevulinic acid on the high affinity uptake of aspartic acid by rat brain synaptosomes","volume":"15","author":"McLoughlin","year":"1984","journal-title":"Gen. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/ana.410020415","article-title":"Delta-aminolevulinic acid: Influences on synaptic GABA receptor binding may explain CNS symptoms of porphyria","volume":"2","author":"Muller","year":"1977","journal-title":"Ann. Neurol."},{"key":"ref_39","first-page":"458","article-title":"The effect of delta-aminolevulinic acid on the synthesis and metabolism of GABA in rabbit brain homogenates","volume":"57","author":"Becker","year":"1980","journal-title":"S. Afr. Med. J."},{"key":"ref_40","first-page":"576","article-title":"Neurochemical aspects of porphyria. Studies on the possible neurotoxicity of delta-aminolaevulinic acid","volume":"49","author":"Shanley","year":"1975","journal-title":"S. Afr. Med. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/0041-008X(86)90371-6","article-title":"Differential effects of inorganic lead and delta-aminolevulinic acid in vitro on synaptosomal gamma-aminobutyric acid release","volume":"86","author":"Minnema","year":"1986","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/j.1471-4159.1981.tb02378.x","article-title":"Delta-aminolaevulinic acid uptake, toxicity, and effect on [14C]gamma-aminobutyric acid uptake into neurons and glia in culture","volume":"36","author":"Percy","year":"1981","journal-title":"J. Neurochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0197-0186(00)00092-9","article-title":"Inhibition of adenylate cyclase activity by 5-aminolevulinic acid in rat and human brain","volume":"38","author":"Emanuelli","year":"2001","journal-title":"Neurochem. Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.brainres.2004.07.071","article-title":"Peripheral oxidative biomarkers constitute a valuable indicator of the severity of oxidative brain damage in acute cerebral infarction","volume":"1025","author":"Liu","year":"2004","journal-title":"Brain Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/ajcn\/62.3.493","article-title":"Mineral requirements of elderly people","volume":"62","author":"Wood","year":"1995","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1093\/clinchem\/34.3.474","article-title":"Trace elements in human clinical specimens: Evaluation of literature data to identify reference values","volume":"34","author":"Iyengar","year":"1988","journal-title":"Clin. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.ijheh.2012.01.002","article-title":"Korea National Survey for Environmental Pollutants in the Human Body 2008: Heavy metals in the blood or urine of the Korean population","volume":"215","author":"Lee","year":"2012","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.envres.2006.06.013","article-title":"Occupational and environmental human lead exposure in Brazil","volume":"103","author":"Paoliello","year":"2007","journal-title":"Environ. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.envpol.2014.03.004","article-title":"Metal composition of fine particulate air pollution and acute changes in cardiorespiratory physiology","volume":"189","author":"Cakmak","year":"2014","journal-title":"Environ. Pollut."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1093\/aje\/kwk073","article-title":"Selenium level and cognitive function in rural elderly Chinese","volume":"165","author":"Gao","year":"2007","journal-title":"Am. J. Epidemiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1093\/gerona\/63.6.635","article-title":"Trace element levels and cognitive function in rural elderly Chinese","volume":"63","author":"Gao","year":"2008","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1097\/JOM.0b013e3181792463","article-title":"Interaction of the delta-aminolevulinic acid dehydratase polymorphism and lead burden on cognitive function: the VA normative aging study","volume":"50","author":"Rajan","year":"2008","journal-title":"J. Occup. Environ. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1056\/NEJMoa022848","article-title":"Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter","volume":"348","author":"Canfield","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1159\/000109891","article-title":"Effects of blood lead levels on cognitive function of older women","volume":"15","author":"Muldoon","year":"1996","journal-title":"Neuroepidemiology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.neuro.2011.10.012","article-title":"Modification by the genes ALAD and VDR of lead-induced cognitive effects in children","volume":"33","author":"Pawlas","year":"2012","journal-title":"Neurotoxicology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.neuro.2006.04.003","article-title":"Possibilities of newer ALAD polymorphism influencing human susceptibility to effects of inorganic lead on the neurobehavioral functions","volume":"28","author":"Chia","year":"2007","journal-title":"Neurotoxicology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1002\/chem.201102786","article-title":"The importance of stereochemically active lone pairs for influencing Pb(II) and As(III) protein binding","volume":"18","author":"Zampella","year":"2012","journal-title":"Chem. Eur. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1107\/S0907444900000597","article-title":"MAD analyses of yeast 5-aminolaevulinate dehydratase: Their use in structure determination and in defining the metal-binding sites","volume":"56","author":"Erskine","year":"2000","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2384","DOI":"10.3390\/nu5072384","article-title":"Iron: Protector or risk factor for cardiovascular disease? 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