Effects of Disulfiram, Cyanamide and 1‐Aminocyclopropanol on the Aldehyde Dehydrogenase Activity in Human Erythrocytes and Leukocytes

Abstract

The effects of the aldehyde dehydrogenase (ALDH; EC 1.2.1.3) inhibitors disulfiram, cyanamide and 1-aminocyclopropanol (ACP) on the ALDH activities in human erythrocytes and leukocytes were studied. Assays were performed by incubating intact or sonicated blood cells in the presence of different concentrations of the inhibitors, using 3,4-dihydroxyphenylacetaldehyde, the aldehyde derived from dopamine oxidation, as the substrate. The amount of acid metabolite formed was measured using high-performance liquid chromatography with electrochemical detection. The erythrocyte ALDH was extremely sensitive to disulfiram, and only about 0.5 microM was needed to cause a 50% inhibition of the activity. The leukocyte activity was less sensitive, and showed a similar degree of inhibition at an 100-fold higher concentration of disulfiram. Cyanamide and ACP were both potent inactivators of the leukocyte ALDH activity, giving a 50% inhibition at concentrations of 10 and 50 microM, respectively, whereas the erythrocyte activity was much less affected. Diethyldithiocarbamate, the reduced metabolite of disulfiram, and coprine, from which ACP is derived, were much less effective inhibitors of the erythrocyte and leukocyte ALDH activities than were disulfiram and ACP.

Role of Aldehyde Dehydrogenase Isozymes in the Defense of Rat Lens and Human Lens Epithelial Cells against Oxidative Stress

“…Cyanamide and the more potent inhibitor, disulfiram, inhibit various ALDH isozymes to different extent and are regarded as general inhibitors of these enzymes. 25,26…”

Distribution of Acetaldehyde in Human Blood: Effects of Ethanol and Treatment With Disulfiram

“…When whole blood was spiked with 10 uM acetaldehyde and mixed with ice-cold PCA in saline solution with 10 sec, 60-90% of the added amount was recovered in the soluble fraction, while the bound amount remained unchanged. In blood samples treated with 100 uM disulfiram (which causes about 90% inhibition of the erythrocyte ALDH) (Helander and Tottmar, 1988) acetaldehyde, the recovery was increased but still not complete (results not shown). Moreover, if the spiked blood was left at room temperature for 30 min prior to precipitation, none of the acetaldehyde added could be recovered, not even in the presence of disulfiram.…”