TY - JOUR
T1 - Urinary delta-ALA
T2 - A potential biomarker of exposure and neurotoxic effect in rats co-treated with a mixture of lead, arsenic and manganese
AU - Andrade, Vanda
AU - Mateus, M. Luísa
AU - Batoréu, M. Camila
AU - Aschner, Michael
AU - dos Santos, A. P.Marreilha
N1 - Funding Information:
The authors wish to thank the financial support by FCT strategic project Pest-OE/SAU/UI4013/2011, for the I-Med.UL, Faculty of Pharmacy, University of Lisbon , and from the National Institute of Health ( NIH ES R01 10563 , P30 ES 000267 ). The authors also wish to thank Doctor Maria Eduarda Mendes for her advises with the atomic absorption spectrometry.
PY - 2013/9
Y1 - 2013/9
N2 - 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 (5. mg/kg), As (60. mg/L), Mn (10. mg/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.
AB - 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 (5. mg/kg), As (60. mg/L), Mn (10. mg/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.
KW - Biomarkers
KW - Delta-aminolevulinic acid
KW - Lead, arsenic and manganese
KW - Metal mixtures
KW - Neurotoxicity
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U2 - 10.1016/j.neuro.2013.06.003
DO - 10.1016/j.neuro.2013.06.003
M3 - Article
C2 - 23764341
AN - SCOPUS:84880341228
VL - 38
SP - 33
EP - 41
JO - NeuroToxicology
JF - NeuroToxicology
SN - 0161-813X
ER -