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 (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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 33-41 |
| Number of pages | 9 |
| Journal | NeuroToxicology |
| Volume | 38 |
| DOIs | |
| State | Published - Sep 2013 |
| Externally published | Yes |
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Keywords
- Biomarkers
- Delta-aminolevulinic acid
- Lead, arsenic and manganese
- Metal mixtures
- Neurotoxicity
ASJC Scopus subject areas
- Neuroscience(all)
- Toxicology
Cite this
Urinary delta-ALA : A potential biomarker of exposure and neurotoxic effect in rats co-treated with a mixture of lead, arsenic and manganese. / Andrade, Vanda; Mateus, M. Luísa; Batoréu, M. Camila; Aschner, Michael; dos Santos, A. P Marreilha.
In: NeuroToxicology, Vol. 38, 09.2013, p. 33-41.Research output: Contribution to journal › Article
}
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
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
UR - http://www.scopus.com/inward/record.url?scp=84880341228&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84880341228&partnerID=8YFLogxK
U2 - 10.1016/j.neuro.2013.06.003
DO - 10.1016/j.neuro.2013.06.003
M3 - Article
VL - 38
SP - 33
EP - 41
JO - NeuroToxicology
JF - NeuroToxicology
SN - 0161-813X
ER -