US EPA

1677581 

Journal Article 

Urinary delta-ALA: A potential biomarker of exposure and neurotoxic effect in rats co-treated with a mixture of lead, arsenic and manganese 

Andrade, V; Mateus, ML; Batoréu, MC; Aschner, M; Marreilha dos Santos, AP 

2013 

1 

NeuroToxicology
ISSN: 0161-813X
EISSN: 1872-9711 

ELSEVIER SCIENCE BV 

AMSTERDAM 

38 

Elsevier 

33-41 

English 

23764341 

10.1016/j.neuro.2013.06.003 

WOS:000325447800006 

https://linkinghub.elsevier.com/retrieve/pii/S0161813X13000971
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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. 

Metal mixtures; Lead, arsenic and manganese; Neurotoxicity; Biomarkers; Delta-aminolevulinic acid