Mechanisms of the inhibitory effects of selenium and mercury on the activity of delta-aminolevulinate dehydratase from mouse liver, kidney and brain.
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 (Se(4+)) and mercuric chloride (Hg(2+)) on the activity of hepatic, renal and cerebral delta-aminolevulinate dehydratase (delta-ALA-D) of adult male mice (Swiss albino). Hg(2+) inhibited delta-ALA-D from tissue supernatants and the IC(50) values for hepatic, renal and cerebral enzyme inhibition were 38+/-4.2, 67.5+/-4.3 and 46.2+/-3.7 microM, respectively. Se(4+) displayed a higher inhibitory action toward delta-ALA-D activity than Hg(2+). Simultaneous addition of Se(4+) and Hg(2+) to the delta-ALA-D assay increased the inhibition of the enzyme. Se(4+) and Hg(2+) oxidized total -SH groups from hepatic, renal and cerebral supernatants, although the effect of Se(4+) decreased in the presence of increasing concentrations of Hg(2+). The oxidation of -SH groups from a dithiol (DTT), a monothiol glutathione (GSH) and a protein (albumin) increased in the presence of Hg(2+). Only DTT was oxidized by Se(4+) and the oxidation decreased in the presence of Hg(2+), suggesting the formation of a chemical complex. This complex did not inhibit delta-ALA-D. These results suggest a similar inhibitory mechanism of Se(4+) and Hg(2+) on delta-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 delta-ALA-D.
Farina
M
M
Curso de Farmácia, Centro de Ciências da Saúde, Universidade Regional Integrada-Campus de Erechim, 99700-000, Erechim RS, Brazil. marcelofarina@zipmail.com.br
Brandão
R
R
Lara
F S
FS
Soares
F A A
FA
Souza
D O
DO
Rocha
J B T
JB
D000818:Animals; D001921:Brain / Q000201:enzymology*; D007668:Kidney / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008627:Mercuric Chloride / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D010084:Oxidation-Reduction; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018038:Sodium Selenite / Q000494:pharmacology* / Q000633:toxicity; D013438:Sulfhydryl Compounds / Q000378:metabolism
D013438:Sulfhydryl Compounds; D008627:Mercuric Chloride; D000623:Porphobilinogen Synthase; D018038:Sodium Selenite