Diphenyl diselenide and diphenyl ditelluride differentially affect δ-aminolevulinate dehydratase from liver, kidney, and brain of mice

In the present study, the inhibitory effect of diphenyl diselenide and diphenyl ditelluride after in vitro, acute (a single dose), or chronic exposure (14 doses) was examined in mice 24 hours after the last administration. In vitro, diphenyl diselenide, and diphenyl ditelluride inhibited δ‐aminolevu...

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Published in:Journal of biochemical and molecular toxicology 2000, Vol.14 (6), p.310-319
Main Authors: Maciel, E. N., Bolzan, R. C., Braga, A. L., Rocha, J. B. T.
Format: Article
Language:English
Subjects:
Animals
Benzene Derivatives - pharmacology
Body Weight - drug effects
Brain - drug effects
Brain - enzymology
Diphenyl Diselenide
Diphenyl Ditelluride
Dithiothreitol - metabolism
Environmental Exposure
Glutathione - metabolism
Kidney - drug effects
Kidney - enzymology
Kinetics
Liver - drug effects
Liver - enzymology
Male
Mice
Organ Size - drug effects
Organometallic Compounds - pharmacology
Organoselenium Compounds - pharmacology
Porphobilinogen Synthase
Porphobilinogen Synthase - antagonists & inhibitors
Selenium
Tellurium
Tellurium - pharmacology
Thiol Oxidation
δ-Aminolevulinate Dehydratase
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Summary:In the present study, the inhibitory effect of diphenyl diselenide and diphenyl ditelluride after in vitro, acute (a single dose), or chronic exposure (14 doses) was examined in mice 24 hours after the last administration. In vitro, diphenyl diselenide, and diphenyl ditelluride inhibited δ‐aminolevulinate dehydratase (δ‐ALA‐D) from brain, liver, and kidney with a similar potency (IC50 5–10 μM), and at 120 μM, they increased the rate of dithiothreitol (DTT) and reduced glutathione (GSH) oxidation. After a single dose (sc), diphenyl diselenide (1 mmol/kg) inhibited the liver (22%, p < 0.01) and brain (27%, p < 0.01) δ‐ALA‐D, but it did not inhibit the kidney enzyme. After a single dose (sc), diphenyl ditelluride (0.5 mmol/kg) inhibited liver (46%, p < 0.01), kidney (21%, p < 0.05), and brain (39%, p < 0.01) δ‐ALA‐D. Chronic exposure to diphenyl diselenide (0.125 and 0.250 mmol/kg) caused significant (p < 0.05) increase in liver and liver‐to‐body weight ratio and inhibited liver (40 and 60%, respectively) and brain (21 and 40%, respectively) δ‐ALA‐D. Kidney δ‐ALA‐D was not inhibited significantly after exposure to diphenyl diselenide. Total nonprotein −SH concentration was decreased only in liver of animals exposed for 14 days to selenide. Chronic exposure to diphenyl ditelluride (0.010 and 0.025 mmol/kg) caused significant (p < 0.05) inhibition of liver (28 and 42%, respectively) and brain (23 and 54%, respectively) δ‐ALA‐D. Kidney δ‐ALA‐D was not inhibited significantly by diphenyl ditelluride. Total nonprotein −SH concentration was decreased to a different extent after acute or chronic treatment with diphenyl ditelluride depending on analyzed tissue. Hemoglobin content was decreased significantly by 17 and 22% after chronic treatment with 0.125 and 0.25 mmol/kg diphenyl diselenide, respectively. Chronic exposure to 0.010 mmol/kg diphenyl ditelluride caused a reduction of 17% in hemoglobin content that tended to be significant (p < 0.10). These results suggest that δ‐ALA‐D inhibition after exposure to organochalcogens may perturb heme‐dependent metabolic pathway and contribute to the toxicological properties of these compounds. © 2000 John Wiley & Sons, Inc. J Biochem Mol Toxicol 14:310–319, 2000
ISSN:1095-6670
1099-0461
DOI:10.1002/1099-0461(2000)14:6<310::AID-JBT3>3.0.CO;2-D