INFLUENCE OF CHRONIC ALCOHOL-ABUSE AND LIVER-DISEASE ON HEPATIC ALDEHYDE DEHYDROGENASE-ACTIVITY

Alcohol metabolism results in the production of acetaldehyde, a compou nd that is much more toxic than ethanol itself. Hepatic aldehyde dehyd rogenase (ALDH) is the main enzymatic system responsible for acetaldeh yde clearance from the hepatocyte. The objective of this study was to determine the modifications in ALDH activity due to chronic alcohol ab use and liver disease. ALDH activity was determined in samples of live r tissue from 69 alcoholic and 82 nonalcoholic subjects, with and with out liver disease. According to the results of liver pathology examina tion, alcoholic patients were classified into the following groups: co ntrols, with no liver disease (group 1), noncirrhotic liver disease pa tients (group 2), and cirrhotics (group 3). Nonalcoholic subjects were categorized, using the same criteria, into groups 4, 5, and 6, respec tively. ALDH activity was determined spectrophotometrically at two sub strate concentrations: 18 mM for total activity and 180 mu M for low K -m activity. High K-m activity was calculated by subtracting the low K -m activity value from that of total ALDH activity. Results obtained i n each group were expressed as the mean +/- SD of mU of g of wet weigh t. There were no significant differences when the total ALDH activity from the alcoholic and the nonalcoholic patients with a similar degree of liver pathology were compared: group 1, 1257 +/- 587 vs. group 4, 1328.1 +/- 546.2 (p: NS); group 2, 919.1 +/- 452.4 vs. group 5, 753.5 +/- 412 (p:NS); and group 3, 430.2 +/- 162.4 vs. group 6, 473.2 +/- 22 5.3 (p: NS). On the other hand, total ALDH activity was significantly lower in cirrhotics than in controls, both among alcoholics (p < 0.01) and among nondrinkers (p < 0.05). The low K-m activity was severely r educed in cirrhotics, both alcoholics and nonalcoholics (p < 0.01). Hi gh K-m activities in cirrhotic patients were low, compared to controls , both in alcoholics and nonalcoholics, although the difference was no nsignificant. The results of the present study suggests that chronic a lcohol abuse does not depress ALDH activity. A reduction in the ALDH a ctivity detected in patients with severe liver disease (cirrhotics) wa s clearly a consequence of liver damage. This reduction was due mainly to a decrease of the low K-m ALDH activity, but a trend to a decrease in the high K-m ALDH activity was also detected. (C) 1998 Elsevier Sc ience Inc.