Effects of Common Bile Duct Ligation on Serum and Hepatic Arylesterase Activity in Ethanol Intoxicated Rats

다국어 초록 (Multilingual Abstract)

Arylesterase is a polymorphic aromatic esterase and organopohosphatase. Determination of the enzyme activities in human plasma is applied in the diagnosis of cirrhosis and carcinoma of the liver. Ethanol disposal is thought to produce metabolic disorders resulting in alcoholic liver disease. To investigate the mutual effects of ethanol disposal and cholestasis induced by common bile duct (CBD) ligation on the activities of arylesterase, we have determined the enzyme activities in the rat hepatic (cytosolic, mitochondrial and microsomal) preparations as well as in the rat serum by using ten animal models: normal rats (group 1), sham operated rats (group 2), CBD-ligated rats (group 3), chronic ethanol-intoxicated rats (group 4), sham operation with chronic ethanol intoxication (group 5), CBD ligation with chronic ethanol into-xication (group 6), acute ethanol intoxication 1.5 hr and 24 hr (group 7A and 7B), and acute ethanol intoxication 1.5 h and 24 h with CBD ligation (group 8A and 8B). We have estimated the enzyme activities for 14 d (group 2-6), 1.5h (group 1, 3, 7A and 8A), and 24 h (group 1, 3, 7B and 8B) post-ligation. The values of Km and Vmax. for these hepatic preparations of cholestatic rat liver combined with chronic ethanol intoxication were also measured by using phenyl acetate as the substrate from the 14 d post-ligation. Arylesterase activities of hepatic preparations and in the cholestatic rat serum (group 3) showed significant decrease compared to the activities from sham-operated control (group 2). Enzyme kinetic parameters indicated that Vmax for all the hepatic preparations in the cholestatic rat (group 3) decreased significantly, although the Km values were about the same as in sham-operated control (group 2). The synergic effects of cholestasis and ethanol intoxication on the decrease in the arylesterase activity were significant in the microsomal preparation from the cholestatic rat liver as well as in the serum combined with chronic ethanol intoxication (group 6). The synergic reduction of enzymaic kinetic parameters was significant in the Vmax values of the cytosolic and microsomal preparation, as well as in the serum analyzed in group 6, and of the cytosolc preparation analyzed in group 8A and 8B, although th Km values did not change. These results, therefore, suggest that the biosynthesis of hepatic arylesterase seems to have decreased when cholestasis was combined with chronic ethanol intoxication. And the synergic reduction in the enzyme activity analyzed in the cholestatsis with ethanol intoxication may reflects that preexisting cellular damages with cholestasis were exacerbated by ethanolinduced oxidative stress.