title: Urinary delta-ALA: a potential biomarker of exposure and neurotoxic effect in rats co-treated with a mixture of lead, arsenic and manganese.
abstract: Lead (Pb), arsenic (As) and manganese (Mn) are neurotoxic elements that often occur in mixtures for which practically no information is available on biomarkers (BMs) for the evaluation of exposure/effects. Exposures to these metals may increase delta-aminolevulinic acid (delta-ALA), which in itself may potentiate neurotoxicity. The objective of this study was to investigate the utility of urinary delta-ALA (delta-ALA-U) levels as BM of exposure and/or neurotoxic effects induced by this mixture. Five groups of Wistar rats were treated for 8 days with Pb (5mg/kg), As (60mg/L), Mn (10mg/kg), the 3-metal mixture (same doses of the single metals), and control group. Motor activity was evaluated and 24-h urine collected before and after the treatment. 24-hours (h) after the last dose, the rats were sacrificed and the brains removed for analyses. Delta-ALA and metal levels were determined in brain and urine. Co-treated rats showed a significant (p<0.05) correlation between increased Pb, As, Mn and delta-ALA levels in the brain and decreased motor activity. Delta-ALA-U concentrations were higher in the mixture-treated group than the sum of the delta-ALA-U levels in each single-treated groups and discriminated (p<0.05) between the mixture and untreated rats. Moreover, delta-ALA-U was correlated (p<0.05) with brain delta-ALA levels. These results establish that treatments with this metal mixture exacerbate behavioral dysfunction, increasing most prominently brain Pb levels. This study is the first to establish that delta-ALA-U levels represent a sensitive BM of exposure/neurotoxic effect to this metal mixture.
authors.affiliation: i-Med-UL, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
authors.forename: Vanda
authors.initials: V
authors.lastname: Andrade
authors.forename: M Luísa
authors.initials: ML
authors.lastname: Mateus
authors.forename: M Camila
authors.initials: MC
authors.lastname: Batoréu
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
authors.forename: A P Marreilha
authors.initials: AP
authors.lastname: dos Santos
mesh_terms: D000622:Aminolevulinic Acid / Q000378:metabolism / Q000652:urine*; D000818:Animals; D001151:Arsenic / Q000633:toxicity* / Q000652:urine; D015415:Biomarkers / Q000652:urine; D001921:Brain / Q000378:metabolism; D007854:Lead / Q000633:toxicity* / Q000652:urine; D008297:Male; D008345:Manganese / Q000633:toxicity* / Q000652:urine; D009043:Motor Activity / Q000187:drug effects; D051381:Rats
chemical_list: D015415:Biomarkers; D007854:Lead; D008345:Manganese; D000622:Aminolevulinic Acid; D001151:Arsenic
keywords: Biomarkers; Delta-aminolevulinic acid; Lead, arsenic and manganese; Metal mixtures; Neurotoxicity