Chemico-Biological Interactions 165 (2007) 127–137
Cadmium inhibits -aminolevulinate dehydratase from rat lung
in vitro: Interaction with chelating and antioxidant agents
Cristiane Luchese
a
, Gilson Zeni
a
, Jo˜ ao B.T. Rocha
a
,
Cristina W. Nogueira
a
, Francielli W. Santos
a,b,∗
a
Departamento de Qu´ ımica, Centro de Ciˆ encias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria,
CEP 97105-900, RS, Brazil
b
Centro de Ciˆ encias da Sa ´ ude de Uruguaiana (UNIPAMPA), Universidade Federal de Santa Maria, Uruguaiana,
CEP 97500-009, RS, Brazil
Received 26 September 2006; received in revised form 20 November 2006; accepted 21 November 2006
Available online 24 November 2006
Abstract
The effect of cadmium (Cd
2+
) on -aminolevulinate dehydratase (-ALA-D) activity from rat lung in vitro was investigated.
-ALA-D activity, a parameter for metal intoxication, has been reported as a target of Cd
2+
in different tissues. The protective effect
of monotherapies with dithiol chelating (meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonic acid
(DMPS)) or antioxidant agents (ascorbic acid, diphenyl diselenide (PhSe)
2
, and N-acetylcysteine (NAC)) was evaluated. The effect
of a combined therapy (dithiol chelating × antioxidant agent) was also studied. Zinc chloride (ZnCl
2
) and dithiothreitol (DTT) were
used to investigate the mechanisms involved in cadmium, chelating and antioxidant effects on -ALA-D activity. Cadmium inhibited
rat lung -ALA-D activity at low concentrations. DTT (3 mM), but not ZnCl
2
(100 M), protected the inhibition of enzyme activity
caused by Cd
2+
. Chelating agents were not effective in restoring the enzyme activity. DMPS and DMSA presented inhibitory effect
on enzyme activity. DTT restored the inhibition caused by both chelating agents, but ZnCl
2
restored only the inhibitory effect induced
by DMSA. These compounds caused a marked potentiation of -ALA-D inhibition induced by Cd
2+
. ZnCl
2
did not restore inhibition
of enzyme activity caused by Cd
2+
plus chelating agents. Conversely, DTT restored the inhibition induced by Cd
2+
/DMSA, but
not by Cd
2+
/DMPS. Antioxidants were not effective in ameliorating -ALA-D inhibition induced by Cd
2+
, whereas ascorbic acid
potentiated the enzyme inhibition induced by this metal. A combined effect of Cd
2+
× DMPS × (PhSe)
2
and Cd
2+
× DMPS × NAC
was observed. There was no combined effect of Cd
2+
× chelator × antioxidants when DMSA was used. This study demonstrated
that Cd
2+
inhibited -ALA-D activity and chelating and antioxidant agents, alone or combined, did not restore the enzyme activity.
In contrast, these compounds potentiated the inhibition induced by Cd
2+
in rat lung.
© 2006 Elsevier Ireland Ltd. All rights reserved.
Keywords: Cadmium; -ALA-D; Chelating agents; Antioxidant; Selenium; Lung
∗
Corresponding author at: Centro de Ciˆ encias da Sa ´ ude de Urugua-
iana (UNIPAMPA), Universidade Federal de Santa Maria, 97500-009
Uruguaiana, RS, Brazil. Tel.: +55 55 3411 5174;
fax: +55 55 3220 8978.
E-mail address: francielliweber@yahoo.com.br (F.W. Santos).
1. Introduction
The exposure of human population to a variety of
heavy metals has been a public health concern [1].
Several metals are known to disturb cellular functions
by binding to thiol groups of biomolecules. Cadmium
(Cd
2+
) is one of the most abundant non-essential ele-
0009-2797/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.cbi.2006.11.007