Search

The different concentrations of ethanol (20-100%) and distilled water extract for Dendropanax morbifera LEV. leaves were evaluated to induce antioxidant and biological activity employed by variety of assays. The 20%, 80%, and 100% ethanol extract demonstrated the relatively higher activity, whereas distilled water, 40%, and 60% ethanol extracts exhibited the lower antioxidant and biological activity. Especially, 80% ethanol extract showed the remarkably higher radical scavenging activity, reducing power, total phenol and flavonoid content, α-glucosidase, and tyrosinase inhibitory activity, and alcohol dehydrogenases (ADH) and aldehyde dehydrogenase (ALDH) activity. Also, 100% ethanol extract exhibited relatively greater activity, but there did not show significant radical scavenging activity. Furthermore, there were 50% and 30% promotion effect for ADH activity assay and 80% and 40% promotion effect for ALDH activity assay in 80% and 100% ethanol extract, respectively. In addition, in the minimum inhibitory concentration (MIC), all extracts except for distilled water extract inhibited Bacillus cereus, Staphylococcus aureus subsp. aureus, Escherichia coli. For Pichia jadinii, whole extracts effectively inhibited yeast multiplication at concentration of 125 μg/mL for 100% ethanol extract and 250 μg/mL for the rest of extract. These result indicated that D. morbifera LEV. leaves extracted by 80% ethanol would be the ideal extracting solution to maximize inherent antioxidant and biological activity agent.

Although many factors related to the pathogenesis of alcoholic liver disease have been considered, 1) hepatotoxic effects of ethanol and its metabolites, 2) effects of excessive hepatic NADH generation, 3) hypoxia, 4) alterations of the immune system, 5) genetic factors, and 6) nutritional factors may play more important roles to produce alcoholic liver disease. Recently, genetic polymorphism of key enzymes related to metabolism of ethanol and acetaldehyde, alcohol dehydrogenase, cytochrome P4502E1 and aldehyde dehydrogenase, have been discovered. On the other hand, an assay system for hepatitis C virus (HCV) markers has been developed and a high frequency of HCV markers in alcoholics with liver disease has been reported. In this review, we focus on recent gains in our knowledge of pathogenesis of alcoholic liver disease, and discuss the relationship between alcoholic liver disease and HCV, and treatment of alcoholic liver disease.

Concurrent use of alcohol and other drugs is a serious problem. Cocaine is the most frequently abused drug overseas. An increasing number of cases demonstrating concurrent use of alcohol and cocaine is being noted. Alcohol preference (AP) in animals is an index of human drinking behavior. In this study brain monoamine and alcohol metabolism were studied to clarify the mechanisms of changes in AP following single or repeated cocaine administration. To inbred strain of mouse, C57BL/6J, 10% alcohol and tap water were given and AP was measured following intraperitoneal cocaine administration once or repeatedly for one week. Then the rate of blood alcohol disappearance in vivo (beta value) and liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity in vitro were measured. Changes in brain norepinephrine, dopamine, serotonin and their metabolites were also measured. A single cocaine administration reduced the AP of C57BL/6J mice. beta value was not changed after pretreatment with cocaine. The level of brain dopamine was increased only two hours after cocaine administration. In repeated cocaine administration, AP was reduced after cocaine administration. Brain monoamine levels were not changed. Neither the beta value nor liver ADH, ALDH activity was changed after either single or repeated cocaine administration. It is speculated that reduced AP is associated with an increase in brain dopamine and changes in AP did not contribute to alcohol metabolism pharmacologically. Dopaminergic system makes a rule of, in part, alcohol drinking behavior.

The purpose of this study is to clarify the relationship between hereditary predisposition and social-psychological factors in terms of drinking behavior of Japanese male students. The subjects were 123 male students who belonged to athletic clubs of K university in 1993. Regular drinking was evaluated as "drinking at home or with intimate friends" and party drinking as "drinking at club parties". On the two drinking occasions, the frequency and amount of drinking, and social drinking behavior were evaluated. Problem drinking behavior was investigated by a modified version of Aoyama's questionnaire (1984). Low Km aldehyde dehydrogenase (ALDH2) activity was evaluated by the facial flushing response to alcohol and the ethanol patch test. Evaluable results of the ethanol test as well as replies of the questionnaire were obtained from 109 students. Twenty-three students positive for both the facial flushing response to alcohol and the ethanol patch test were considered to be flushers, and 42 negative for both to be non-flushers. The non-flushers consumed a higher amount of alcohol than the flushers did on drinking occasions at home or with intimate friends. The number of problem drinking behavior items in the non-flushers was significantly higher than that in the flushers and increased with the amount and frequency of drinking. The ratio of students who had inappropriate drinking motivations, began to drink by themselves, or continued to offer alcohol to drinkers showing flushing even when they declined it, was significantly higher in the non-flushers than in the flushers. In addition, non-flushers showing such social drinking behavior drank more than those not showing such behavior. The frequency of positive or inappropriate drinking behavior was significantly lower in the flushers than in the non-flushers. However, the amount and frequency of drinking and problem drinking behavior were similar in the flushers and non-flushers. These results indicate that social drinking behavior of non-flushers influences not only themselves but also other drinkers, and that drinking of flushers is strongly influenced by social factors.

Purine nucleotide degradation during ethanol catabolism, inhibition of renal excretion of urate by lactic acid, and high purine content of certain kinds of beverage are responsible for the elevation of serum uric acid level following alcohol drinking. It is well documented that rapid consumption of ATP produces uric acid via purine nucleotide degradation. Since individuals with ALDH2*1 can catalyze ethanol readily, they consume large amount of ATP, and thus produce more hypoxanthine than those with ALDH2*2. Thus, daily drinker and heavy drinker tend to readily induce hyperuricemia after alcohol ingestion. A high purine content in beer may contribute to the increasing frequency of hyperuricemia. Restriction of any kind of alcohol beverages, especially beer, is necessary in the medical control of patients with gout or hyperuricemia.

Administration of latamoxef and cefoperazone, reported to act like disulfiram in humans, caused a depression of mitochondrial low Km aldehyde dehydrogenase (low Km ALDH) activity in rats. In addition, a marked increase of blood acetaldehyde concentration was observed when rats were given alcohol orally at 18 hours after administration of these cephalosporins. However, mitochondrial low Km ALDH activity and blood acetaldehyde level were not altered by repeated administration of 300 mg and 1,000 mg of cefclidin (CFCL, E1040) or E1077 per kg. From these results, it was concluded that neither CFCLn or E1077 affected the alcohol metabolizing-system.

The present study was carried out to examine the effect of single or consecutive administration of T-2588 on liver of male rat injured by the administration of D-galactosamine X HCl. The T-2588 was orally given to hepatic-injured rats at doses of 125 mg/kg and 1,000 mg/kg singly or for consecutive 5 days. A 10 ml/kg dose of the vehicle was orally given to control rats. The results obtained were summarized below. Single administration of T-2588. Twenty-four hours after a single administration of T-2588, the liver taken from control rats apparently indicated galactosamine-induced hepatitis. No drug-related alterations were observed in hepatic functional test, liver weight and histological examinations at either dose of T-2588. Galactosamine-induced hepatitis was not affected by a single administration of T-2588. Consecutive administration of T-2588. Twenty-four hours after a 5-consecutive-day administration of T-2588, galactosamine-induced hepatitis in control rats was restored to the normal state. The cure of galactosamine-induced hepatitis was not affected by a 5-consecutive-day administration of T-2588. The hepatic aldehyde dehydrogenase activity in hepatic-injured rats was not affected by a 5-consecutive-day administration of T-2588.

A study on disulfiram-like reaction of T-2588 was carried out using Sprague-Dawley male rats. A 500 mg/kg/day dose of T-2588 was given orally to 14 male rats once daily for 7 days. Disulfiram (200 mg/kg/day X 3 days, p.o.), cephalexin (CEX) (500 mg/kg/day X 7 days, p.o.) and cefmetazole (CMZ) (500 mg/kg/day X 7 days, i.v.) were used as the positive control and 2 comparative controls, respectively. The results obtained were summarized below. Each parameter (aldehyde dehydrogenase activity and the blood aldehyde level) in the disulfiram-like reaction was not affected by the T-2588 administration. A marked inhibition of aldehyde dehydrogenase activity (low-Km ALDH, Enzyme I) and a significant increase of the blood aldehyde level were observed in the rats receiving disulfiram. No drug-related disulfiram-like reaction was induced in the male rats receiving CEX, while alterations similar to the disulfiram action were recognized in rats receiving CMZ.