The role of thiol-reducing agents on modulation of glutamate binding induced by heavy metals in platelets.

Abstract

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.

• Authors: V C Borges, C W Nogueira
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 22 Issue 2 Pg. 438-43 (Mar 2008) ISSN: 0887-2333 [Print] England
• PMID: 18068946 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chelating Agents
• Metals, Heavy
• Reducing Agents
• Sulfhydryl Compounds
• Cadmium
• Dimercaprol
• Lead
• Glutamic Acid
• Unithiol
• Mercury
• Dithiothreitol

Topics

• Adult
• Blood Platelets (drug effects, metabolism)
• Cadmium (antagonists & inhibitors, toxicity)
• Chelating Agents (toxicity)
• Dimercaprol (pharmacology)
• Dithiothreitol (pharmacology)
• Female
• Glutamic Acid (metabolism)
• Humans
• In Vitro Techniques
• Lead (toxicity)
• Male
• Mercury (antagonists & inhibitors, toxicity)
• Metals, Heavy (antagonists & inhibitors, toxicity)
• Reducing Agents (pharmacology)
• Sulfhydryl Compounds (pharmacology)
• Unithiol (toxicity)