The role of thiol-reducing agents on modulation of glutamate binding induced by heavy metals in platelets.
In the present study, we investigated if thiol-reducing agents are capable of altering mercury (Hg2+), lead (Pb2+) and cadmium (Cd2+) effects on platelet glutamatergic system. Dimercaprol (BAL), a dithiol chelating agent therapeutically used for the treatment of heavy metals poisoning, was capable of protecting the [3H]-glutamate binding against the effects caused by Pb2+ and Hg2+. 2,3-Dimercaptopropane-1-sulfonic acid (DMPS), another dithiol-reducing chelating agent, was capable of protecting the effect caused by Cd2+, Pb2+ and Hg2+. The similar effect was observed with addition of dithiothreitol (DTT) on [3H]-glutamate binding in human platelets. Dithiol-reducing agents (BAL, DMPS and DTT) alone did not alter [3H]-glutamate binding. In contrast, reduced glutathione (GSH), a monothiol-reducing agent, caused a significant inhibition on [3H]-glutamate binding at all concentrations tested. GSH did not modify heavy metal effects on [3H]-glutamate binding in platelets. The findings of the present investigation indicate that dithiol-reducing agents are capable of altering Hg2+, Pb2+ and Cd2+ effects on platelet glutamatergic system. In vitro data on chelating-metal interactions provide only an estimated guide to the treatment of heavy metal poisoning. Consequently, more studies in intoxicated patients are necessary to determine the precise use of the peripheral models and chelating agents.
Borges
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Departamento de Química, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil. vcorralo@yahoo.com.br
Nogueira
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D000328:Adult; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002104:Cadmium / Q000037:antagonists & inhibitors / Q000633:toxicity; D002614:Chelating Agents / Q000633:toxicity; D004112:Dimercaprol / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007854:Lead / Q000633:toxicity; D008297:Male; D008628:Mercury / Q000037:antagonists & inhibitors / Q000633:toxicity; D019216:Metals, Heavy / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D019163:Reducing Agents / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D014494:Unithiol / Q000633:toxicity
D002614:Chelating Agents; D019216:Metals, Heavy; D019163:Reducing Agents; D013438:Sulfhydryl Compounds; D002104:Cadmium; D004112:Dimercaprol; D007854:Lead; D018698:Glutamic Acid; D014494:Unithiol; D008628:Mercury; D004229:Dithiothreitol