Kinetic parameters of the inhibition of red blood cell aminolevulinic acid dehydratase by triethyl lead and its reversal by dithiothreitol and zinc

Yagminas, Al; Villeneuve, D. C.

doi:10.1002/jbt.2570020205

Cited by 7 publications

(1 citation statement)

References 17 publications

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“…In fact, the d-ALA-D reactivation index was more strongly correlated to BLLs than d-ALA-D activity. Although the use of the d-ALA-D reactivation index as an indicator of the effects of lead was previously suggested (Yagminas and Villeneuve, 1987), most studies on leadexposed workers have only used d-ALA-D activity as a subclinical indicator of lead effects (Gürer-Orhan et al, 2004). d-ALA-D inhibition could contribute to the toxic effects of lead, since the accumulation of its substrate, d-aminolevulinic acid, may generate reactive oxygen species leading to oxidative damage in proteins and DNA (Daggett et al, 1998;Monteiro et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Blood thioredoxin reductase activity, oxidative stress and hematological parameters in painters and battery workers: relationship with lead and cadmium levels in blood

Conterato

Bulcão

Sobieski

et al. 2011

J of Applied Toxicology

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Oxidative stress has been shown to be involved in lead and cadmium toxicity. We recently showed that the activity of the antioxidant enzyme thioredoxin reductase (TrxR) is increased in the kidneys of lead-exposed rats. The present study evaluated the blood cadmium and blood lead levels (BLLs) and their relationship with hematological and oxidative stress parameters, including blood TrxR activity in 50 painters, 23 battery workers and 36 control subjects. Erythrocyte δ-aminolevulinate dehydratase (δ-ALA-D) activity and its reactivation index were measured as biomarkers of lead effects. BLLs increased in painters, but were even higher in the battery workers group. In turn, blood cadmium levels increased only in the painters group, whose levels were higher than the recommended limit. δ-ALA-D activity was inhibited only in battery workers, whereas the δ-ALA-D reactivation index increased in both exposed groups; both parameters were correlated to BLLs (r = -0.59 and 0.84, P < 0.05), whereas the reactivation index was also correlated to blood cadmium levels (r = 0.27, P < 0.05). The changes in oxidative stress and hematological parameters were distinctively associated with either BLLs or blood cadmium levels, except glutathione-S-transferase activity, which was correlated with both lead (r = 0.34) and cadmium (r = 0.47; P < 0.05). However, TrxR activity did not correlate with any of the metals evaluated. In conclusion, blood TrxR activity does not seem to be a good parameter to evaluate oxidative stress in lead- and cadmium-exposed populations. However, lead-associated changes in biochemical and hematological parameters at low BLLs underlie the necessity of re-evaluating the recommended health-based limits in occupational exposure to this metal.

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Section: Discussionmentioning

confidence: 99%

Blood thioredoxin reductase activity, oxidative stress and hematological parameters in painters and battery workers: relationship with lead and cadmium levels in blood

Conterato

Bulcão

Sobieski

et al. 2011

J of Applied Toxicology

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A comparison of the effects of inorganic and alkyllead compounds on human erythrocytic δ‐aminolevulinic acid dehydratase (ALAD) activity in vitro

Burns

Godwin

1991

J of Applied Toxicology

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A study comprising two experiments comparing the effects of the alkyllead compounds triethyllead acetate and tetraethyllead as well as an inorganic lead compound (Pb(NO&) on human erythrocytic 6-aminolevulinic acid dehydratase activity was undertaken. In Experiment I , four human blood samples were pre-incubated for 0 min or 60 min with increasing concentrations (0-1000 pM) of triethyllead acetate, tetraethyllead and Pb(N03)*, and the 6-aminolevulinic acid dehydratase activity was determined. There was no discernible inhibitory effect of tetraethyllead at any concentration, with or without pre-incubation. Pb(N03)2 showed a distinct effect at an addition concentration of I pM, with a substantial inhibition only following pre-incubation. Triethyllead acetate showed no difference in effect with pre-incubation. In the second experiment, the activating effects of zinc chloride (60 p M ) and dithiothreitol (20 mM) on 6-aminolevulinic acid dehydratase activity were examined on four human blood samples in the presence of varying concentrations of Pb(N03)z (0-50 pM) and triethyllead acetate (0-1000 pM). The addition of zinc chloride alone showed little effect on enzyme activity, while dithiothreitol alone caused a substantial activation of the enzyme at all lead concentrations. The addition of both zinc chloride and dithiothreitol caused an even greater activation of the enzyme. The data indicate that Pb(NOJ)2 is a much more potent inhibitor of 6-aminolevulinic acid dehydratase activity than triethyllead acetate (Ki values of 0.77 p M versus 130.37 pM, respectively). The use of 6-aminolevulinic acid dehydratase activity as an indicator of exposure may be questionable in cases of alkyllead exposure. Possible causes for differences in the inhibition of 6-aminolevulinic acid dehydratase by these compounds is also discussed.

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Biochemical Effects of Pesticides on Mammals

Khan

1990

Chemistry of Plant Protection

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Kinetic parameters of the inhibition of red blood cell aminolevulinic acid dehydratase by triethyl lead and its reversal by dithiothreitol and zinc

Cited by 7 publications

References 17 publications

Blood thioredoxin reductase activity, oxidative stress and hematological parameters in painters and battery workers: relationship with lead and cadmium levels in blood

Blood thioredoxin reductase activity, oxidative stress and hematological parameters in painters and battery workers: relationship with lead and cadmium levels in blood

A comparison of the effects of inorganic and alkyllead compounds on human erythrocytic δ‐aminolevulinic acid dehydratase (ALAD) activity in vitro

Biochemical Effects of Pesticides on Mammals

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