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Mechanisms of the inhibitory effects of selenium and mercury on the activity of δ-aminolevulinate dehydratase from mouse liver, kidney and brain

2003; Elsevier BV; Volume: 139; Issue: 1 Linguagem: Inglês

10.1016/s0378-4274(02)00454-x

1879-3169

Marcelo Farina, Rodrigo Martins Brandão, Fabiana S de Lara, Félix Alexandre Antunes Soares, Diogo O. Souza, João Batista Teixeira da Rocha,

Porphyrin Metabolism and Disorders

Mercury is known to interact with selenite and when the two are co-administered, one reduces the toxicity of the other. The main goal of this study was to investigate the simultaneous in vitro effects of sodium selenite (Se4+) and mercuric chloride (Hg2+) on the activity of hepatic, renal and cerebral δ-aminolevulinate dehydratase (δ-ALA-D) of adult male mice (Swiss albino). Hg2+ inhibited δ-ALA-D from tissue supernatants and the IC50 values for hepatic, renal and cerebral enzyme inhibition were 38±4.2, 67.5±4.3 and 46.2±3.7 μM, respectively. Se4+ displayed a higher inhibitory action toward δ-ALA-D activity than Hg2+. Simultaneous addition of Se4+ and Hg2+ to the δ-ALA-D assay increased the inhibition of the enzyme. Se4+ and Hg2+ oxidized total SH groups from hepatic, renal and cerebral supernatants, although the effect of Se4+ decreased in the presence of increasing concentrations of Hg2+. The oxidation of SH groups from a dithiol (DTT), a monothiol glutathione (GSH) and a protein (albumin) increased in the presence of Hg2+. Only DTT was oxidized by Se4+ and the oxidation decreased in the presence of Hg2+, suggesting the formation of a chemical complex. This complex did not inhibit δ-ALA-D. These results suggest a similar inhibitory mechanism of Se4+ and Hg2+ on δ-ALA-D in which oxidation of sulfhydryl groups located at the active site of the enzyme is an essential step. Furthermore, decreasing oxidative effects of selenite on sulfhydryl groups from DTT in the presence of mercury are believed to occur as the result of the formation of an inactive ternary complex of the thiol–Hg–Se type, which does not inhibit δ-ALA-D.