Effects of high taurocholate load on activities of hepatic alcohol metabolizing enzymes

Abstract

Membrane-associated cytotoxicity induced by hydrophobic bile salts is a major contributing factor leading to liver diseases. Administration of ursodeoxycholate reduces serum liver enzymes in chronic liver diseases but the nature of this effect is still unclear. Using alcohol metabolising enzymes as cellular markers, the hepatotoxic properties of hydrophobic bile salts and the putative hepatoprotective effect of ursodeoxycholate was examined. Two animal models of biliary retention, bile duct obstruction and choledochocaval fistula was used to investigate the effect of taurocholate on the hepatic alcohol metabolizing enzymes: cytosolic alcohol dehydrogenase, microsomal ethanol oxidizing system, catalase and aldehyde dehydrogenase before and after the infusion of taurocholic acid or tauroursodeoxycholic acid for two days period. Bile duct obstruction was found to be similar to or slightly exceeds choledochocaval fistula in the degree of retention. Following the taurocholic acid infusion, the serum alcohol dehydrogenase activity as well as microsomal ethanol oxidizing system and aldehyde dehydrogenase were greatly increased but the level of cytosolic alcohol dehydrogenase and catalase activities was found to be lower in either or both models in comparison with the control animals. However, the tauroursodeoxycholic acid infusion did not induce any significant changes in the levels of all the alcohol metabolizing enzyme activities in either or both models. These findings suggest that hydrophobic taurocholic acid (7α α α α) affects the plasmalemma to allow leakage of cytosolic alcohol dehydrogenase into the blood circulation, stimulates the biosynthesis of microsomal ethanol oxidizing system and aldehyde dehydrogenase, and suppresses the biosynthesis of alcohol dehydrogenase and catalase. But in contrast, the hydrophilic tauroursodeoxycholic acid (7β β β β) provided hepatoprotective effect.

Glycoprotein Isolated from Acanthopanax senticosus Protects against Hepatotoxicity Induced by Acute and Chronic Alcohol Treatment

“…ADH activities were determined using cytosolic fractions. 7) MEOS activities were determined using microsomal fractions. 7) ALDH activities were measured spectrophotometrically at 340 nm using acetaldehyde and NAD ϩ as the substrates following NADH production.…”

“…7) MEOS activities were determined using microsomal fractions. 7) ALDH activities were measured spectrophotometrically at 340 nm using acetaldehyde and NAD ϩ as the substrates following NADH production. 9) Enzyme activities were expressed as nM of NADH formed/min/mg of protein in ADH, nM of NADH formed/min/mg of protein in MEOS and nM of NADH formed/min/mg of protein in ALDH.…”

“…[6][7][8] The process is catalyzed by 3 different enzymes: alcohol dehydrogenase (ADH), microsomal ethanol metabolizing system (MEOS), and acetaldehyde dehydrogenase (ALDH). Since acetaldehyde is much more toxic than alcohol, it is associated with a larger number of the metabolic abnormalities in liver disease induced by alcohol.…”

Influence of Alcohol Consumption on Oxidative Stress and Antioxidant Status in Cancer Patients - Case-control Study from Western Nepal

“…Although exact incidence of different cancers in Nepal is not yet available, preliminary studies suggest that lung, oral cavity and stomach in males, and cervix, breast and lung in females are the most common type of cancers in Nepal (Binu et al, 2007;Pradhananga et al, 2009) Alcohol promotes the generation of reactive oxygen species and interferes with the body's normal defense mechanism. 80-90% of alcohol breakdown in the liver results in the formation of acetaldehyde whose further metabolism in the cells leads to reactive oxygen species production (ROS) (Kim and Shin, 2002;Pronko et al, 2002). Acetaldehyde itself is a mutagenic and carcinogenic by product.…”

Evaluation of the antioxidant effects of <i>Ziziphus mauritiana</i> lam. leaf extracts against chronic ethanol-induced hepatotoxicity in rat liver

“…About 80-90% of ingested alcohol is metabolized in the liver, where alcohol is oxidized to acetaldehyde (Kim and Shin, 2002;Pronko et al, 2002). The process is catalyzed by three different enzymes: alcohol dehydrogenase (ADH), microsomal ethanol metabolizing system (MEOS) and acetaldehyde dehydrogenase (ALDH) (Lieber, 2000).…”