• 약학회지
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• 제40권1호
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• pp.78-83
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• 1996

An ethanol administration causes hepatic triglyceride accumulation in rats. To assess whether the herbal extract containing Phaseoli radiati semen(herbal extract) inhibit s the triglyceride accumulation in the liver, we determined the hepatic triglyceiide levels in rats fed ethanol and the herbal extract. In addition, the blood ethanol concentrations and the activities of hepatic alcohol dehydrogenase(ADH) and aldehyde dehydrogenase(ALDH) were measured to determine the effects of the herbal extract on alcohol metabolism in rats. The administration of the herbal extract markedly reduced the triglyceride levels elevated by ethanol in the liver as well as in the serum. The herbal extract remarkably lowered blood ethanol concentrations in a dose-dependent manner. The ADH activities decreased by ethanol were recovered to the normal level by the herbal extract treatment. Moreover, the ALDH activities slightly decreased by ethanol increased beyond the normal level by the herbal extract treatment. We conclude that the herbal extract inhibits the hepatic triglyceride accumulation and stimulates alcohol metabolism by preventing ADH and ALDH from inhbition by the ethanol administration in the rat liver.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1987년도 Proceedings of Korea-Japan Panax Ginseng Symposium 1987 Seoul Korea
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• pp.47-58
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• 1987

Ethanol exerts different effects on hepatic cellular metabolism, depending mainly on the duration of its intake. In the presence of ethanol following an acute load, a number of hepatic functions are inhibited, including lipid oxidation and microsomal drug metabolism. In its early stages, chronic ethanol consumption produces adaptive metabolic changes in the endoplasmic reticulum which result in increased metabolism of ethanol and drugs and accelerated lipoprotein production. Prolongation of ethanol intake may result in injurious hepatic lesions such as alcoholic hepatitis and cirrhosis A number of such metabolic effects of ethanol are directly linked to the two major products of its oxidation; hydrogen and acetaldehyde. The excess hydrogen from ethanol unbalances the liver cell's chemistry. In the presence of excess hydrogen ions the process is turned in a different direction. In this study, it was attempted to observe the effect of ginseng saponins on alcohol Oehydrogenase(ADH), aldehyde dehydrogenase(ALDH) and microsomal ethanol oxidizing system(MEOS) in vivo as well as in vitro. Furthermore, the effect of ginseng saponin on the hydrogen balance in the liver and the hepatic cellular distribution of (1-14C) ethanol, its incorporation into acetaldehyde and lipids was also investigated. It seemed that ginseng saponin stimulated the above enzymes and other related enzymes in ethanol metabolism, resulting in a rapid removal of acetaldehyde and excess hydrogen from the animal body,

• 약학회지
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• 제53권2호
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• pp.69-73
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• 2009

Acute betaine treatment induces time-dependent changes in the hepatic glutathione (GSH), cysteine and S-adenosylmethionine (SAM) levels. Our previous study demonstrated that betaine administered $1{\sim}4$ hours prior to sacrifice decreased hepatic GSH levels, but these levels were increased when measured 24 hours following the treatment. The present study was aimed to determine dose-dependent effects of betaine on hepatic metabolism of sulfur amino acid in mice. Mice were sacrificed 2.5 or 24 hours after intraperitoneal treatment with betaine at different dose levels ranging from 50 to 1000 mg/kg. The concentrations of methionine and SAM were increased by a betaine dose of 100 mg/kg, and the concentrations of GSH and cysteine were decreased by a betaine dose of 200 mg/kg at 2.5 hours. These changes were augmented with increasing doses of betaine. At 24 hours following betaine treatment, increased GSH and decreased taurine levels were observed from dose levels of 400 mg/kg. Changes in hepatic activities of cystathionine beta-synthase, gammaglutamylcysteine ligase and cysteine dioxygenase were observed from dose levels of $200{\sim}400$ mg/kg of betaine administered 24 hours prior to sacrifice.

• Toxicological Research
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• 제13권4호
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• pp.377-383
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• 1997

To investigate the circadian variation in the bromobenzene metabolism, bromobenzene(400 mg/kg body weight) was intraperitoneally administered to the rats every other day for 6 days both in the night; 24:00 and the day; 12:00. Each group of animals was sacrificed at 8hr after last injection of bromobenzene. The contents of hepatic CYP were more increased in control rats of night phase than those of day phase but in case of bromobenzene treatment there were no differences in hepatic CYP between rats of the night phase and those of day phase and the injection of prednisolon inhibited the hepatic CYP content in rats. Furthermore, the decreasing rate of hepatic glutathione contents to the control was higher in rats of day phase than those of night phase by the bromobenzene treatment. And the hepatic glutathione S-transferase activities were increased both in control and bromobenzene treated rats of the night phase than those of day phase. On the other hand, liver weight per body weight(%), hepatic lipid peroxide content, serum levels of alanine aminotransferase were more increased both in bromobenzene-treated and control rats of the night phase than those in the day phase. These results indicate that the rats of night phase may induce more accelerated formation of bromobenzene 3,4-oxide from bromobezene than those of day phase in rats.

• 한국환경보건학회지
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• 제23권2호
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• pp.83-88
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• 1997

To evaluate the effect of bromobenzene pretreatment on the bromobenzene metabolism, the animal group was induced the stage of slight liver damage with 7 times bromobenzene injection every two days (400 mg/kg body wt. i.p.). In the present experimental animal model, the single dose of bromobenzene(400 mg/kg body wt. i.p.) was injected to the bromobenzene-pretreated rats and the hepatic aniline hydroxylase(AH) activity, glutathione(GSH) content and glutathione S-transferase (GST) activity were determined at the intervals of 2, 4, 8, 24 hours throughout 24 hr. The activities of hepatic AH and GST were generally higher in bromobenzene-pretreated rats than those in normal group throughout the whole course of experiment. Furthermore, the decreasing rate of hepatic GSH content was also higher in bromobenzene pretreated rats than in normal rats. Moreover, the value of V$_{max}$ in hepatic GST was higher in bromobenzene pretreated rats than that in the normal rats. In conclusion, these results indicate that the pretreatment of bromobenzene may rather enhance the bromobenzene metabolism.

• Journal of Nutrition and Health
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• 제37권5호
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• pp.347-351
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• 2004

This study was carried out to investigate the supplementary effects of ${\gamma}$-oryzanol extracted from rice bran on lipid metabolism in diabetic mice. We supplied 2 kinds of experimental diets (CO without and GO with 0.2％ ${\gamma}$-oryzanol) to diabetic mice for 8 weeks. Diet intake, body weight, organ weight, contents of serum and hepatic lipid profiles, and fecal lipid levels were measured. Though there was no significant difference in diet intake, body weight change and organ weight between experimental groups, the concentration of serum total cholesterol and hepatic total lipid, total cholesterol and HMG-CoA reductase activity was significantly lower in GO group treated with 0.2％ ${\gamma}$-oryzanol of diet than CO group after supplementary period of experimental diets. And total lipid, triglyceride, total cholesterol, and bile acid levels excreted to feces were significantly higher in GO group than CO group. These results suggest that ${\gamma}$-oryzanol decrease the serum and hepatic lipid levels by lowing HMG-CoA reductase activity or increasing the contents of fecal lipid in diabetic KK mice.

• 한국식품영양학회지
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• 제12권1호
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• pp.33-38
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• 1999

This study was conducted to investigate the synergic effect of dietary selenium and methionine levels on hepatic lipid metabolism in ethanol treated rats. Sprague-Dawley male rats were fed diets containing three levels of methionine(0,3 and 9g/kg diet) with or without selenium(0.45mg/kg diet). Ethanol was administered with 25%(v/v) ethanol orally at the same time once a day in ethanol group and isocalori sucrose was administered to the control group. The rate were sacrificed after 5 and 10 weeks of feeding period. Glutathione content was decreased by ethanol treatment and significantly increased in proportion to level of dietary methionine and was higher in selenium deficiency group than that of selenium admin-istration group. Lipid peroxide content was significantly increased in deficiency of both methionine and selenium(LMet-Se+EtOH) group. Total lipid triglyceride and cholesteol contents in liver were increas-ed and phospholipid content was decreased in ethanol treated group and ethanol treatment accelerated those increment and decrement in methionine deficiency(LMt) group and excessive methionine admin-istration(HMet)group.

• Toxicological Research
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• 제31권2호
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• pp.137-149
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• 2015

Human hepatocytes, with complete hepatic metabolizing enzymes, transporters and cofactors, represent the gold standard for in vitro evaluation of drug metabolism, drug-drug interactions, and hepatotoxicity. Successful cryopreservation of human hepatocytes enables this experimental system to be used routinely. The use of human hepatocytes to evaluate two major adverse drug properties: drug-drug interactions and hepatotoxicity, are summarized in this review. The application of human hepatocytes in metabolism-based drug-drug interaction includes metabolite profiling, pathway identification, P450 inhibition, P450 induction, and uptake and efflux transporter inhibition. The application of human hepatocytes in toxicity evaluation includes in vitro hepatotoxicity and metabolism-based drug toxicity determination. A novel system, the Integrated Discrete Multiple Organ Co-culture (IdMOC) which allows the evaluation of nonhepatic toxicity in the presence of hepatic metabolism, is described.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제24권6호
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• pp.518-527
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• 2021

Purpose: The incidence of hepatic steatosis among children has been increasing; however, data distinguishing simple steatosis from a more complex disorder are lacking. Methods: This study identified the etiologies resulting in hepatic steatosis through a retrospective review of pediatric liver biopsies performed in the last 10 years. A total of 158 patients with hepatic steatosis proven by histopathological evaluation were enrolled in the study, and baseline demographic features, anthropometric measurements, physical examination findings, laboratory data, ultrasonographic findings, and liver histopathologies were noted. Results: The two most common diagnoses were inborn errors of metabolism (IEM) (52.5%) and nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) (29.7%). The three most common diseases in the IEM group were glycogen storage disorders, Wilson's disease, and mitochondrial disease. The rates of consanguineous marriage (75.6%; odds ratio [OR], 26.040) and positive family history (26.5%; OR, 8.115) were significantly higher (p=0.002, p<0.001, respectively) in the IEM group than those in the NAFLD/NASH group. Younger age (p=0.001), normal anthropometric measurements (p=0.03), increased aspartate aminotransferase levels (p<0.001), triglyceride levels (p=0.001), and cholestatic biochemical parameters with disrupted liver function tests, as well as severe liver destruction of hepatic architecture, cholestasis, fibrosis, and nodule formation, were also common in the IEM group. Conclusion: Parents with consanguinity and positive family history, together with clinical and biochemical findings, may provide a high index of suspicion for IEM to distinguish primary steatosis from the consequence of a more complex disorder.

• Journal of Pharmaceutical Investigation
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• 제22권3호
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• pp.219-227
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• 1992

The influence of phenobarbital (PB) pretreatment (75 mg/kg/day, i.p. for 4 days) on the pharmacokinetics of diltiazem (DTZ) and its metabolite, desacetyldiltiazem (DAD), was investigated in rats. DTZ was injected via femoral (3 mg/kg) or portal (10 mg/kg) vein to the control and PB-pretreated rats. DAD was also injected separately via femoral (3 mg/kg) vein to both groups of rats. The intrinsic hepatic plasma clearance of DTZ was found to be significantly increased (6.8-fold) by the PB pretreatment. However, the fraction of an intravenous DTZ dose converted to DAD $(F_mi)$ was only slightly (6%) increased and calculated metabolic rate constant of DTZ to DAD was not affected by the pretreatment. On the other hand, plasma free fraction of DTZ was increased (1.8-fold) from $4.24{\pm}0.25%$ to $7.45{\pm}0.54%$ by the pretreatment. However, the l.8-fold increase in the free fraction of DTZ would not explain the 6.8-fold increase in the hepatic intrinsic clearance of DTZ. Therefore, the increase in either the hepatic blood flow or the metabolism other than to DAD was expected as the probable mechanism(s) of the increased hepatic clearance of DTZ. Sequential metabolism of DAD to further metabolites, however, would be a more potential cause of the apparently unchanged metabolism of DTZ to DAD by the PB-pretreatment.