Brecher A S, Adamu M T
Department of Chemistry, Bowling Green State University, Ohio 43403, USA.
Dig Dis Sci. 2001 Sep;46(9):2033-42. doi: 10.1023/a:1010668005729.
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.
鉴于乙醛处理过的肝素抗凝作用增强，对其他糖胺聚糖（GAGs），如硫酸软骨素A和C、硫酸皮肤素（硫酸软骨素B）、硫酸乙酰肝素和透明质酸，在暴露于乙醛前后进行了抗凝活性测试。在1.8、3.0、3.6或4.5微克肝素（0.32、0.54、0.64、0.81单位肝素）存在的情况下，测试了人血浆Ci-Trol凝血对照品I级（百特医疗保健公司）的凝血时间。此外，分别使用9、27或90微克的硫酸软骨素A、B或C代替肝素。研究了在44.7 mM乙醛存在下，分别为2微克肝素（0.36单位）、硫酸软骨素A、B和C（各20微克）、2微克硫酸乙酰肝素和2微克透明质酸对血浆凝血时间的影响。观察到硫酸皮肤素（硫酸软骨素B）延长了血浆的凝血时间，尽管程度小于肝素。硫酸软骨素A和C、硫酸乙酰肝素和透明质酸未延长凝血时间。然而，尽管这些糖胺聚糖本身缺乏抗凝作用，但用乙醛对所有硫酸化糖胺聚糖进行预处理后得到的产物增强了乙醛的抗凝作用。相比之下，透明质酸对凝血时间没有影响，其经乙醛处理的产物也没有影响。此外，乙醇对糖胺聚糖-血浆混合物的凝血时间没有影响。这些结果表明，硫酸化糖胺聚糖可能被慢性酒精中毒患者血浆中的一种成分乙醛所修饰，并且产生的产物可能导致凝血时间延长。
