heparitin-sulfate and Alcoholism

In view of the increased anticoagulant effect of acetaldehyde-treated heparin, other glycosaminoglycans (GAGs) such as chondroitin sulfates A and C, dermatan sulfate (chondroitin sulfate B), heparan sulfate, and hyaluronic acid were tested for anticoagulant activity before and after exposure to acetaldehyde. Clotting times of human plasma Ci-Trol coagulation control, level I (Baxter Healthcare Corp.), were tested in the presence of 1.8, 3.0, 3.6, or 4.5 microg heparin (0.32, 0.54, 0.64, 0.81 units heparin). Additionally, 9, 27, or 90 microg of chondroitin sulfates A, B, or C was utilized in lieu of heparin. The effects of 2 microg heparin (0.36 units), chondroitin sulfates A, B, and C, (20 microg each), 2 microg heparan sulfate, and 2 microg hyaluronic acid, respectively, in the presence of 44.7 mM acetaldehyde on the clotting time of plasma were studied. It was observed that chondroitin sulfate B (dermatan sulfate) prolonged the clotting time of plasma, although to a lesser extent than heparin. Chondroitin sulfates A and C, heparan sulfate, and hyaluronic acid did not prolong clotting time. However, pretreatment of all the sulfated GAGs with acetaldehyde gave products that enhanced the anticoagulant effect of acetaldehyde, notwithstanding the lack of anticoagulant effect of the GAGs. In contrast, hyaluronic acid exhibited no effect upon clotting time nor did its acetaldehyde-treated product. Furthermore, ethanol exhibited no effect upon the clotting times of the GAG-plasma mixtures. These results suggest that sulfated GAGs may be modified by acetaldehyde, a component of plasma in chronic alcoholics, and that the resultant products may contribute to the prolonged clotting times.

Topics: Acetaldehyde; Alcoholism; Blood Coagulation; Blood Coagulation Tests; Chondroitin Sulfates; Dermatan Sulfate; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid

The extractable and nonextractable collagen and glycosaminoglycuronans (GAG) were estimated and characterized in 32 dried, defatted human livers obtained at necropsy. 10 had normal livers. 22 of the 32 livers were from patients who drank in excess: 5 had fatty livers, 7 had alcholic hepatitis, and 10 had cirrhosis. Livers with alcoholic hepatitis or cirrhosis had significantly increased total and 1 N NaCl-extractable collagen. Only alcoholic hepatitis livers had significantly increased Tris-buffer-extractable GAG, but the amino acid composition of these GAG (proteoglycans) was no different from that of normal livers. The major fraction of these GAG had isoelectric pH (pI)

Topics: Alcoholism; Amino Acids; Chemical and Drug Induced Liver Injury; Chondroitin; Chromatography, Gel; Collagen; Connective Tissue; Dialysis; Fatty Liver; Glucosamine; Glycoproteins; Glycosaminoglycans; Heparitin Sulfate; Hexosamines; Humans; Hyaluronic Acid; Hydroxyproline; Isoelectric Focusing; Liver; Liver Cirrhosis