Effect of disulfiram (DS) on mitochondria from rat hippocampus: Metabolic compartmentation of DS neurotoxicity |
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| Authors: | John Simonian Dipak Haldar Elizabeth Delmaestro Louis D Trombetta |
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| Institution: | (1) Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, 11439 Jamaica, NY;(2) Department of Biological Sciences, St. John's University, 11439 Jamaica, NY |
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| Abstract: | This experiment was designed to study the acute effects of disulfiram on mitochondrial enzymes in nonsynaptic and synaptic mitochondria from rat hippocampus. Cytochromec oxidase, monoamine oxidase-B, glycerolphosphate acyltransferase and betahydroxybutyrate dehydrogenase were studied. Differences in enzyme activity were seen in controls. Cytochromec oxidase activity was higher in synaptic mitochondria whereas glycerolphosphate acyltransferase activity was higher in nonsynaptic mitochondria. Mitochondria from disulfiram treated rats, particularly synaptic mitochondria, exhibited lower specific activities of cytochromec oxidase and monoamine oxidase-B. These alterations were not limited to either the inner or outer mitochondrial membrane. Transmission electron microscopy revealed that mitochondria from disulfiram treated rats were severely altered in isolated preparations as well as in those from whole tissue. This study shows that disulfiram exerts a differential effect on mitochondrial subpopulations. |
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| Keywords: | Disulfiram dithiocarbamates neurotoxicology hippocampus mitochondria |
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