Use of leukocyte aldehyde dehydrogenase activity to monitor inhibitory effect of disulfiram treatment.
Aldehyde dehydrogenase (ALDH; EC 1.2.1.3) activity was determined in leukocytes and erythrocytes from alcoholic patients during different stages of disulfiram (Antabuse) treatment. Assays were performed by incubating intact isolated blood cells in phosphate-buffered saline (pH 7.4, 37 degrees C), using 3,4-dihydroxyphenylacetaldehyde (DOPAL), the biogenic aldehyde derived from dopamine, as substrate. The ALDH activity was assessed from the amount of 3,4-dihydroxyphenylacetic acid (DOPAC) formed, as analysed by high-performance liquid chromatography with electrochemical detection. The leukocyte ALDH, which is similar to the liver "mitochondrial" low-Km ALDH isozyme, was maximally inhibited (about 40-60%) within 2 to 3 days after the initial disulfiram administration (dosage 200 or 400 mg/day orally). The time to reach maximum inhibition (about 95%) of the erythrocyte ALDH, which closely resembles the liver "cytosolic" high-Km isozyme, varied from 3 to more than 6 days. When medication was completed, the leukocyte ALDH activity remained unaltered for the first 2 days, and did not revert to normal levels until about 6 to 7 days after terminating treatment. The erythrocyte ALDH was still inhibited by about 90% 1 week after the last disulfiram administration. These results suggest that the leukocyte ALDH activity might provide an easily accessible marker for monitoring effect and time course of ALDH inhibition during disulfiram treatment.
Helander
A
A
Department of Zoophysiology, Uppsala University, Sweden.
Carlsson
S
S
D000079:Acetaldehyde / Q000378:metabolism; D000328:Adult; D000437:Alcoholism / Q000097:blood / Q000188:drug therapy / Q000201:enzymology*; D000444:Aldehyde Dehydrogenase / Q000097:blood*; D004221:Disulfiram / Q000494:pharmacology*; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance
D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde; D004221:Disulfiram