Influence of chronic alcohol abuse and liver disease on hepatic aldehyde dehydrogenase activity.
Vidal F. Toda R. Gutierrez C. Broch M. Fernandez-Muixi F. Lorenzo A. Richart C.
Department of Internal Medicine, Hospital Universitari de Tarragona JOAN XXIII, Facultat de Medicina i Ciencies de la Salut (Reus), Universitat Rovira i Virgili, Spain.
Alcohol metabolism results in the production of acetaldehyde, a compound that is much more toxic than ethanol itself. Hepatic aldehyde dehydrogenase (ALDH) is the main enzymatic system responsible for acetaldehyde clearance from the hepatocyte. The objective of this study was to determine the modifications in ALDH activity due to chronic alcohol abuse and liver disease. ALDH activity was determined in samples of liver tissue from 69 alcoholic and 82 nonalcoholic subjects, with and without liver disease. According to the results of liver pathology examination, alcoholic patients were classified into the following groups: controls, with no liver disease (group 1), noncirrhotic liver disease patients (group 2), and cirrhotics (group 3). Nonalcoholic subjects were categorized, using the same criteria, into groups 4, 5, and 6, respectively. ALDH activity was determined spectrophotometrically at two substrate concentrations: 18 mM for total activity and 180 microM for low Km activity. High Km activity was calculated by subtracting the low Km activity value from that of total ALDH activity. Results obtained in each group were expressed as the mean +/- SD of mU of g of wet weight. 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 +/- 225.3 (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 Km activity was severely reduced in cirrhotics, both alcoholics and nonalcoholics (p < 0.01). High Km activities in cirrhotic patients were low, compared to controls, both in alcoholics and nonalcoholics, although the difference was nonsignificant. The results of the present study suggests that chronic alcohol abuse does not depress ALDH activity. A reduction in the ALDH activity detected in patients with severe liver disease (cirrhotics) was clearly a consequence of liver damage. This reduction was due mainly to a decrease of the low Km ALDH activity, but a trend to a decrease in the high Km ALDH activity was also detected.
Coagulation inhibitors in alcoholic liver cirrhosis.
Raya-Sanchez JM. Gonzalez-Reimers E. Rodriguez-Martin JM. Santolaria-Fernandez F. Molina-Perez M. Rodriguez-Moreno F. Martinez-Riera A.
Dpto. de Medicina Interna, Hospital Universitario de Canarias, La Laguna, Tenerife, Canary Islands, Spain.
In the present study we have analyzed the relationship between coagulation inhibitors (antithrombin III, protein C and S, thrombomodulin), liver function impairment, and plasma activity of the endothelium-derived proteins plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) in 27 alcoholic cirrhotic patients and 25 controls. Cirrhotics showed decreased values of all the mentioned parameters except for thrombomodulin, PAI-1, and t-PA. Thrombomodulin and t-PA levels were higher in cirrhotics. No relationship was observed between thrombomodulin and t-PA or PAI-1. Protein C and antithrombin III levels were significantly lower in Child's C patients, whereas no correlation was found between t-PA and thrombomodulin and hepatic function derangement. PAI-1 activity was normal in our patients.
Ethanol enhances cholesterol synthesis and secretion in human hepatomal cells.
Visioli F. Monti S. Colombo C. Galli C.
University of Milan, Institute of Pharmacological Sciences, Italy. firstname.lastname@example.org
Excessive consumption of alcohol leads to severe alterations of lipid metabolism, including hyperlipemia and hypercholesterolemia. Following these epidemiological observations, we investigated the effects of ethanol at the cellular level by employing a human hepatomal cell line (HepG2) and by evaluating the biosyntheses of lipid classes from different labeled precursors. Incubation of cells with 2% ethanol resulted in a decreased labeling of phospholipids and in an increase in cholesterol synthesis and secretion. Triglyceride synthesis was increased by ethanol but their secretion in the medium was reduced, suggesting that these alterations may be related to their accumulation in the liver. The alcohol-induced alterations of lipid metabolism are not due to its metabolite acetaldehyde and data suggest that alcohol enhances cholesterol synthesis by affecting the initial steps without increasing HMGCoA expression. The observed modifications of lipid metabolism in HepG2 may partially explain the enhanced incidence of cardiovascular disorders that has been associated with alcoholism.