Effect of organic forms of selenium on delta-aminolevulinate dehydratase from liver, kidney, and brain of adult rats.
The inhibitory effect of various forms of organic selenium compounds and of diphenyl ditelluride (PhTe)2 on delta-aminolevulinate dehydratase (delta-ALA-D) from liver, kidney, and brain of rats was investigated because it has been reported that organocalcogens catalyze the oxidation of thiols. Diphenyl diselenide (PhSe)2, rho-chloro-diphenyl diselenide (rho ClPhSe)2, propyl-2-2-diphenyl diselenide, and propyl-2-methoxy-2-phenyl selenide inhibited delta-ALA-D and the IC50 ranged from 2 to 32 microM depending on the selenium compound and whether it was preincubated with the enzyme. (rho ClPhSe)2 was the most potent inhibitor of delta-ALA-D, and preincubation increased the inhibitory potency of all the tested compounds. Inorganic selenium compounds (sodium selenite, Na2SeO3 and selenium dioxide, SeO2) inhibited delta-ALA-D, and the potency of SeO2 was greater than that of (rho ClPhSe)2. Diphenyl ditelluride (PhTe)2 also inhibited delta-ALA-D but with relatively lower potency than that of organic and inorganic selenium compounds. The inhibitory effect of propyl-2-2-diphenyl diselenide and propyl-2-methoxy-2-phenyl selenide seems to be mediated by (PhSe)2 since the compounds decomposed rapidly to (PhSe)2 in aqueous medium. The inhibitory action of selenium forms on delta-ALA-D from liver, kidney, and brain was antagonized by sulfhydryl protecting agents (dithiotreitol and reduced glutathione). The effects of organic selenium compounds on delta-ALA-D were related to the stability of the Se-Se (or Se-C) bond because the compound methyl-diphenyl diselenide (which possesses the most stable Se-C-Se bond) did not inhibit the enzyme. The inhibitory action of (PhSe)2 was not related to the formation of oxyradicals in the medium since superoxide dismutase and catalase did not affect the inhibition of delta-ALA-D by (PhSe)2. delta-ALA-D from cucumber leaves was not inhibited by selenium or tellurium compounds which suggests that these compounds act directly on the B or beta-site of the animal enzyme. These results suggest that delta-ALA-D from liver, kidney, and brain is a potential molecular target for the toxic effect of organic forms of selenium and tellurium.
Barbosa
N B
NB
Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Santa Maria, RS, Brasil.
Rocha
J B
JB
Zeni
G
G
Emanuelli
T
T
Beque
M C
MC
Braga
A L
AL
D000818:Animals; D001555:Benzene Derivatives / Q000633:toxicity; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D004229:Dithiothreitol / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D016566:Organoselenium Compounds / Q000633:toxicity*; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D013329:Structure-Activity Relationship; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D001555:Benzene Derivatives; D016566:Organoselenium Compounds; D013439:Sulfhydryl Reagents; C061132:diphenyldiselenide; D000623:Porphobilinogen Synthase; D005978:Glutathione; D004229:Dithiothreitol