OBJECTIVETo investigate the expression of the lysosomal enzyme acid sphingomyelinase (ASMase) in alcohol-induced hepatic fibrosis using a rat model.

METHODSThe model of liver fibrosis was induced by administration of alcohol and high fat diet using 20 rats. Six rats given no alcohol and normal diet served as the control group. Real-time PCR, western blotting, and immunohistochemistry were used to evaluate fibrosis-related changes in the mRNA and protein expressions of ASMase.

RESULTSThe fibrotic liver tissues of the model rats showed significantly higher expression levels of ASMase than the non-fibrotic liver tissues of the control rats (P less than 0.05).

CONCLUSIONExpression of ASMase is increased in the fibrotic liver tissue of an alcohol-induced hepatic fibrosis rat model, suggesting that this lysosomal enzyme may contribute to development of this disease condition.

Animals ; Liver ; enzymology ; Liver Cirrhosis, Alcoholic ; enzymology ; Liver Cirrhosis, Experimental ; enzymology ; Male ; Rats ; Rats, Sprague-Dawley ; Sphingomyelin Phosphodiesterase ; metabolism

Animals ; Cyclooxygenase 2 ; Humans ; Isoenzymes ; genetics ; physiology ; Liver ; enzymology ; Liver Cirrhosis ; etiology ; Liver Diseases, Alcoholic ; etiology ; Membrane Proteins ; Prostaglandin-Endoperoxide Synthases ; genetics ; physiology

The effects of ethyl alcohol and pig serum administration on the development of preneoplastic hepatic enzyme-altered foci were examined in an in vivo mid-term assay system. Rats were initially given a single dose (200 mg/Kg) intraperitoneal injection of diethylnitrosamine (DEN). Two weeks later, treatment was started with 10% ethanol + 10% sucrose solution, 10% sucrose solution, or tap water as drinking water for 6 weeks with or without intraperitoneal injection of porcine serum twice a week. All rats were subjected to a two-thirds partial hepatectomy at week 3. The modification potentials were evaluated by comparing the number and area per cm2 of glutathione S-transferase placental form-positive (GST-P+) foci in the liver of each group. As a result, ethanol significantly enhanced the development of GST-P+ foci. Unfortunately, the porcine serum injection produced no hepatic fibrosis and no significant alteration in GST-P+ foci.
Animals ; Diethylnitrosamine/*toxicity ; Ethanol/*pharmacology ; Glutathione Transferase/*metabolism ; Immune Sera/pharmacology ; Liver Cirrhosis, Alcoholic/enzymology ; Male ; Placenta/drug effects/*enzymology ; Precancerous Conditions/*chemically induced/enzymology ; Rats ; Rats, Inbred F344 ; Survival Rate ; Swine

Alcohol is oxidized to acetaldehyde by alcohol dehydrogenase (ADH) and cytochrome P-4502E1 (CYP2E1), and then to acetate by aldehyde dehydrogenase (ALDH). Polymorphisms of these ethanol-metabolizing enzymes may be associated with inter-individual difference in alcohol metabolism and susceptibility to alcoholic liver disease. We determined genotype and allele frequencies of ALDH2, CYP2E1, ADH2, and ADH3 in male Korean patients with alcoholic cirrhosis (n=56), alcoholics without evidence of liver disease (n=52), and nondrinkers (n=64) by using PCR or PCR-directed mutagenesis followed by restriction enzyme digestion. The prevalences of heterozygous ALDH2*1/*2 plus homozygous ALDH2*2/*2 in patients with alcoholic cirrhosis (7.1%) and alcoholics without evidence of liver disease (3.8%) were significantly lower than that in nondrinkers (45.3%). The c2 allele frequencies of the CYP2E1 in alcoholic cirrhosis, alcoholics without evidence of liver disease, and nondrinkers were 0.21, 0.20, and 0.20, respectively. Allele frequencies of ADH2*2 in the three groups were 0.78, 0.74, and 0.77 and those of ADH3*1 were 0.94, 0.98, and 0.95. Therefore, we confirmed the observation that the ALDH2*2 gene protects against the development of alcoholism. However, the development of cirrhosis in Korean alcoholic patients was not associated with polymorphisms of ethanol-metabolizing enzymes.
Adult ; Alcohol Dehydrogenase/*genetics ; Alcoholism/enzymology/genetics ; Aldehyde Dehydrogenase/*genetics ; Central Nervous System Depressants/pharmacokinetics ; Cytochrome P-450 CYP2E1/*genetics ; Ethanol/pharmacokinetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Human ; Korea ; Liver Cirrhosis, Alcoholic/enzymology/*genetics ; Male ; Middle Age ; *Polymorphism (Genetics)

BACKGROUND/AIMS: Genetic variations of ethanol-metabolizing enzymes can affect alcohol drinking behavior. The aims of this study were to investigate and compare the distributions of these genetic polymorphisms between a healthy control group and a heavy drinker group which included an alcoholic liver cirrhosis group. METHODS: Genotypes of ADH2, ALDH2, CYP2E1, and catalase were identified by polymerase chain reaction and restriction fragment length polymorphism. Genomic DNA was extracted from peripheral leukocytes in 42 healthy controls, 12 heavy drinkers, and 30 alcoholic liver cirrhosis patients. RESULTS: 1) The genotype frequencies of ALDH2 (1*1), ADH2 (1*1), CYP2E1 (c1c1), and catalase1 (TT) were 69%, 55%, 38%, and 12%, respectively in healthy Korean males. 2) There was a significant difference in the distribution of the genetic polymorphism of ALDH2 between the control group and heavy drinker group (12 heavy drinkers and 30 alcoholic liver cirrhosis patients). The genotype frequency of ALDH2 mutant, ALDH2 (1*2) and ALDH2 (2*2) in the heavy drinker group (12%) was significantly lower than that in the control group (30%). 3) We didn't find anyone with ALDH2 homozygote mutant (DD) in the heavy drinker group. 4) There was no significant difference in the distribution of genetic polymorphisms in ADH2, CYP2E1 and catalase1 between the two groups. CONCLUSIONS: These results suggest that the absence of ALDH2 mutant genotype is strongly related to heavy drinking behavior. We can not prove, however, any evidence that the polymorphisms of other ethanol-metabolizing enzymes are associated with the determination of alcohol-drinking behavior.
Adult ; Alcohol Dehydrogenase/*genetics ; Alcohol Drinking ; Alcoholism/enzymology/*genetics ; Aldehyde Dehydrogenase/*genetics ; Cytochrome P-450 CYP2E1/*genetics ; Ethanol/metabolism ; Humans ; Liver Cirrhosis, Alcoholic/enzymology/*genetics ; Male ; Middle Aged ; *Polymorphism, Genetic

BACKGROUND/AIMS: To determine the nutritional markers important for assessing the degree of pancreatic insufficiency due to chronic pancreatitis in routine clinical practice. METHODS: A total of 137 patients with chronic pancreatitis were followed up for more than 1 year. They were divided into two groups: a pancreatic diabetes mellitus (DM) group, consisting of 47 patients undergoing medical treatment for DM of pancreatic origin, and a nonpancreatic DM group, consisting of 90 other patients (including 86 patients without DM). Serum albumin, prealbumin, total cholesterol, cholinesterase, magnesium, and hemoglobin were compared between the two groups. RESULTS: The total cholesterol was significantly lower in the pancreatic than the nonpancreatic DM group (164 mg/dL vs 183 mg/dL, respectively; p=0.0028). Cholinesterase was significantly lower in the former group (263 U/L vs 291 U/L, respectively; p=0.016). Among the 37 patients with nonalcoholic pancreatitis, there was no difference in the cholinesterase levels between the pancreatic and nonpancreatic (296 U/L vs 304 U/L, respectively; p=0.752) DM groups, although cholesterol levels remained lower in the former (165 mg/dL vs 187 mg/dL, respectively; p=0.052). CONCLUSIONS: Cholinesterase levels are possibly affected by concomitant alcoholic liver injury. The total cholesterol level should be considered when assessing pancreatic insufficiency due to chronic pancreatitis.
Adult ; Aged ; Aged, 80 and over ; Cholesterol/*blood ; Cholinesterases/blood ; Diabetes Mellitus, Type 2/complications ; Exocrine Pancreatic Insufficiency/*blood/etiology ; Female ; Follow-Up Studies ; Humans ; Liver Cirrhosis, Alcoholic/blood ; Male ; Middle Aged ; Nutritional Status ; Pancreas/enzymology ; Pancreatitis, Alcoholic/blood/complications ; Pancreatitis, Chronic/blood/*complications ; Serum Albumin/analysis