• Korean Journal of Biological Psychiatry
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• v.9 no.1
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• pp.42-49
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• 2002

Objective:This study was to explore the relation of genetic polymorphisms of ALDH2 and CYP2E1 to clinical characteristics of alcoholic patients and alcohol induced liver damage. Methods:The genotype and allele frequencies of 128 male hospitalized patients who met DSM-IV criteria for alcohol dependence were compared with 128 healthy male control subjects. The genetic informations of ALDH2 and CYP2E1 were identified with the technique of polymerase chain reaction and restriction fragment length polymorphism. The clinical characteristics of the alcoholic patients were assessed and analyzed in relation to the family history of alcoholism. For the relation of CYP2E1 genetic polymorphism to the liver damage, the blood levels of various liver function indicators such as ALT, AST, and protein were checked out. Results:1) The alcoholic patients with the family history of alcoholism had the earlier onset of age (p=0.001), the longer duration of illness(p=0.045), and higher NCA scores(p=0.018) than those without the family history of alcoholism. 2) Most alcoholic patients were homozygous for $ALDH2^*1$, compared to control subjects.(p=0.000) 3) There was no difference of CYP2E1 distribution between alcoholic patients and control subjects. However, alcoholic patients having mutant c2 allele showed higher alcoholism severity scores(p=0.004) and more hospitalizations(p=0.014) than those having c1 allele. 4) There was no relationship between CYP2E1 genotype and the functional abnormalities of the liver. Conclusion:This study suggests that $ALDH2^*1$ is highly related with alcohol dependence. Also mutant c2 allele of CYP2E1 is correlated with the severity of alcoholism and the number of hospitalization. But genetic polymorphim of CYP2E1 seems to have no relation to liver damages.

• Biomedical Science Letters
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• v.16 no.1
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• pp.33-38
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• 2010

Culinary herbs and spices have received much attention since they contain high concentrations of bioactive ingredients for antioxidant and anti-inflammatory activities. Protection effect of the herb and spice against acute alcohol consumption has been investigated using zebrafish as a vertebrate model. During 30 days bathed in water containing 1% Et-OH and the designated herb or spice, the survival rate of the Et-OH group was decreased sharply (up to 20% at 10 days). The cinnamon-fed group showed the highest and longer survival rate up to 80% up to for 30 days under the presence of Et-OH, while clove-fed group showed 40% survival rate for 25 days. Et-OH group serum exhibited the weakest antioxidant ability from ferric ion removal ability (FRA) assay; FRA ability was increased in the cinnamon-fed group up to 414%, while the clove and laurel group increased 256% and 309%, respectively. Histologic observation and Oil-red O staining showed hepatic tissue damage was severe in the Et-OH group. The cinnamon- or clove-fed group showed much ameliorated hepatic tissue morphology with minimized steatosis. The cinnamon- or clove-fed group showed lower serum GOT and GPT levels than the Et-OH group. Among hepatic tissue extract, the clove-fed group exhibited the lowest level of GOT and GPT. These results suggest that consumption of cinnamon and clove might be beneficial to attenuate progress of acute fatty liver change by alcohol consumption.

• Food Engineering Progress
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• v.21 no.4
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• pp.318-325
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• 2017

Alcoholic steatosis is a fundamental metabolic disorder and may precede the onset of more severe forms of alcoholic liver disease. In this study, we isolated enzymatichydrolysate from Semisulcospira libertine by alcalase hydrolysis and investigated the protective effect of Semisulcospira libertine hydrolysate on liver injury induced by alcohol in the mouse model of chronic and binge ethanol feeding (NIAAA). In an in vitro study, the hydrolysate protects HepG2 cells from ethanol toxicity. Liver damage was assessed by histopathological examination, as well as by quantitating activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). After the administration of S. libertina hydrolysate, fat accumulation and infiltration of inflammatory cells in liver tissues were significantly decreased in the NIAAA mouse model. The elevated levels of serum AST, ALT, and ALP activities, along with the lipid contents of a damaged liver, were recovered in experimental mice administrated with S. libertina hydrolysate, suggesting its role in blood enzyme activation and lipid content restoration within damaged liver tissues. Moreover, treatment with S. libertine hydrolysate reduced the expression rate of cyclooxygenase (COX-2), interleukin $(IL)-1{\beta}$, and IL-6, which accelerate inflammation and induces tissue damage. All data showed that S. libertine hydrolysate has a preventive role against alcohol-induced liver damages by improving the activities of blood enzymes and modulating the expression of inflammation factor, suggesting S. libertine hydrolysate could be a commercially potential material for the restoration of hepatotoxicity.

• Food Science and Preservation
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• v.13 no.6
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• pp.774-782
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• 2006

This study investigated the hepatoprotective effects of an ethanol extract of lotus root (LRE) on alcohol-induced liver damage in rat. Sprague-Dawley rae weighing $100{\sim}150g$, were divided into 6 groups: basal diet group (BD), alcohol (35% 10 mL/kg/day) teated stoup (ET), LRE 200 mg/kg/day teated group (BD-LREL). LRE 400 mg/kg/day treated group (BD-LREH), LRE 200 mg/kg/day and alcohol treated group (ET-LREL), and LRE 400 3mg/kg/day and alcohol teated group (ET-LREH). After the administration, rats were sacrificed to get serum and liver to analyze antioxidant enzyme activity, glutathione and lipid peroxide contents. The body weight gain and feed efficiency ratio were decreased by alcohol administration, however, were gradually increased to a little lower level than the basal diet group by the combined administration of alcohol and LRE. The serum alanine aminotransferase (ALT), asparate aminotransferase (AST) and alkaline phosphatase (ALP) activities that were elevated by alcohol were significantly decreased by LRE administration. It was also observed that thiobarbituric acid reactive substances (TBARS) content, xanthine oxidase (XO), superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) activities in liver that were increased by alcohol, were markedly decreased in the combined alcohol and LRE administered groups as compared with the alcohol administrated group. These effect of LRE within the alcohol groups were in a dose-dependent manner. The glutathione (GSH) content in liver was decreased by alcohol administration, however, increased after administering LRE. Teken together, these result suggest that ethanol extract of lotus root may have a possible protective effect on liver function in hepatotoxicity-induced rat by alcohol administration.

• Biomolecules & Therapeutics
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• v.21 no.4
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• pp.264-269
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• 2013

Silymarin has been introduced fairly recently as a hepatoprotective agent. But its mechanisms of action still have not been well established. The aim of this study was to make alcoholic fatty liver model of rats in a short time and investigate silymarin's protective effects and possible mechanisms on alcoholic fatty liver for rats. The model of rat's alcoholic fatty liver was induced by intragastric infusion of ethanol and high-fat diet for six weeks. Histopathological changes were assessed by hematoxylin and eosin staining (HE). The activities of alanine transarninase (ALT) and aspartate aminotransferase (AST), the levels of total bilirubin (TBIL), total cholesterol (TC) and triglyceride (TG) in serum were detected with routine laboratory methods using an autoanalyzer. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in liver homogenates were measured by spectrophotometry. The TG content in liver tissue was determined by spectrophotometry. The expression of nuclear factor-${\kappa}B$ (NF-${\kappa}B$), intercellular adhesion molecule-1 (ICAM-1) and interleukin-6 (IL-6) in the liver were analyzed by immunohistochemistry. Silymarin effectively protected liver from alcohol-induced injury as evidenced by improving histological damage situation, reducing ALT and AST activities and TBIL level in serum, increasing SOD and GPx activities and decreasing MDA content in liver homogenates and reducing TG content in liver tissue. Additionally, silymarin markedly downregulated the expression of NF-${\kappa}B$ p65, ICAM-1 and IL-6 in liver tissue. In conclusion, Silymarin could protect against the liver injury caused by ethanol administration. The effect may be related to alleviating lipid peroxidation and inhibiting the expression of NF-${\kappa}B$.

• Food Science of Animal Resources
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• v.37 no.6
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• pp.931-939
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• 2017

Alcoholic liver disease (ALD) is a complex multifaceted disease that involves oxidative stress and inflammation as the key mediators. Despite decades of intensive research, there are no FDA-approved therapies, and/or no effective cure is yet available. Probiotics have received increasing attention in the past few years due to their well-documented gastrointestinal health-promoting effects. Interestingly, emerging studies have suggested that certain probiotics may offer benefits beyond the gut. Lactobacillus fermentum LA12 has been previously demonstrated to play a role in inflammatory-related disease. However, the possible protective effect of L. fermentum LA12 on ALD still remain to be explored. Thus, the aim of this study was to evaluate the possible protective effect of L. fermentum LA12 on alcohol-induced gut barrier dysfunction and liver damage in a rat model of alcoholic steatohepatitis (ASH). Daily oral administration of L. fermentum LA12 in rat model of ASH for four weeks was shown to significantly reduced intestinal nitric oxide production and hyperpermeability. Moreover, small intestinal histological- and qRT-PCR analysis further revealed that L. fermentum LA12 treatment was capable of up-regulating the mRNA expression levels of tight junction proteins, thereby stimulating the restitution of barrier structure and function. Serum and hepatic analyses also revealed that the restoration of epithelial barrier function may prevent the leakage of endotoxin into the blood, subsequently improve liver function and hepatic steatosis in the L. fermentum LA12-treated rats. Altogether, results in this study suggest that L. fermentum LA12 may be used as a dietary adjunct for the prevention and treatment of ASH.

• Journal of Acupuncture Research
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• v.32 no.1
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• pp.13-22
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• 2015

Objectives : Alcohol-related liver disease is a major cause of morbidity and mortality worldwide. The present study was undertaken to determine whether Ganoderma lucidum pharmacopuncture(GLP) could protect against chronic liver injury induced by ethanol intoxication in rats. Methods : Sprague-Dawley rats were divided into 4 groups: normal, control, normal saline pharmacopuncture(NP), and GLP, with 8 animals in each. Each group, except normal, received ethanol orally. The NP and GLP groups were treated daily with NP and GLP respectively. The control group was not treated. All rats except the normal group were intoxicated for 4 weeks by oral administration of EtOH(6 g/kg BW). Two acupuncture points were used: Qimen($LR_{14}$) and Taechung($LR_3$). Body weight, histopathological analysis, liver function, activities of antioxidant enzymes, and immunohistochemistry were assessed. Results : GLP reduced the histological changes due to chronic liver injury induced by EtOH and significantly reduced the increase in the alanine aminotransferase(ALT) and aspartate aminotransferase(AST) enzymes. It significantly reversed the superoxide dismutase(SOD) and the catalase activities(CAT). It also significantly decreased BAX and increased Bcl-2 immunoreactivity expression. Conclusions : This study showed the protective efficacy of GLP against EtOH-induced chronic liver injury in SD rats by modulating ethanol metabolizing enzymes activity, attenuating oxidative stress, and inhibiting mitochondrial damage-mediated apoptosis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.10
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• pp.1347-1352
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• 2009

The effects of methanol extract of barely (Hordeum vulgare) on alcohol-induced damages of liver were investigated in male ICR mice. Mice were divided into three groups, control, ethanol, and ethanol plus 0.15% of barley extract. After four weeks of ethanol feeding, ethanol group significantly increased the P450 content, CYP2E1 and CYP1A2 enzyme activities, whereas ethanol plus barely group markedly decreased to levels similar to control group. Catalase activity in ethanol group was significantly lower than that in control group; however, ethanol plus barely group stimulated catalase activity as well as SOD activity significantly. These results indicated that barely extract modulated P450 enzymes for ethanol-induced liver damage and might be useful in developing functional food for alcoholic liver damage.

• The Korean Journal of Community Living Science
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• v.28 no.4
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• pp.537-546
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• 2017

This study was performed to determine the hepatoprotective effects of ethanol extract of loquat leaf (LL) on alcohol-induced liver damage in rats. Sprague-Dawley rats (n=32) were divided into the following four groups: normal group (NOR), ethanol administrated group (ET), ethanol plus LL 200 mg/kg BW/day administrated group (ET-LLL), and ethanol plus LL 400 mg/kg Bw/day administrated group (ET-LLH). Body weight gain and food intake of the ET group were significantly reduced compared to those of the ET-LLL and ET-LLH groups. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activities elevated by ethanol administration were significantly reduced by LL administration. Serum triglyceride (TG) and total cholesterol (TC) contents and hepatic TG and TC contents of the ET group were significantly elevated compared to those of the NOR group. However, TG and TC contents in the serum and liver were significantly reduced in the ET-LLH group. Hepatic glutathione (GSH) contents of the ET-LLL and ET-LLH groups were significantly elevated, and hepatic thiobarbituric acid reactive substances (TBARS) contents were reduced compared to that of the ET group. Taken together, these results suggest that LL may have a possible protective effect on the improvement of hepatic injury by ethanol administration.

• Archives of Pharmacal Research
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• v.28 no.7
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• pp.791-798
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• 2005

The hepatoprotective activity of flavonol glycosides rich fraction (F-2), prepared from 70% alcohol extract of the aerial parts of V calcarata Desf., was evaluated in a rat model with a liver injury induced by daily oral administration of $CCl_4$ (100 mg/kg, b.w) for four weeks. Treatment of the animals with F-2 using a dose of (25 mg/kg, b.w) during the induction of hepatic damage by $CCl_4$ significantly reduced the indices of liver injuries. The hepatoprotective effects of F-2 significantly reduced the elevated levels of the following serum enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). The antioxidant activity of F-2 markedly ameliorated the antioxidant parameters including glutathione (GSH) content, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), plasma catalase (CAT) and packed erythrocytes glucose-6-phosphate dehydrogenase (G6PDH) to be comparable with normal control levels. In addition, it normalized liver malondialdehyde (MDA) levels and creatinine concentration. Chromatographic purification of F-2 resulted in the isolation of two flavonol glycosides that rarely occur in the plant kingdom, identified as quercetin-3,5-di-O-$\beta$-D-diglucoside (5) and kaempferol-3,5-di-O-$\beta$-D-diglucoside (4) in addition to the three known compounds identified as quercetin-3-O-$\alpha$-L-rhamnosyl- (${\rightarrow}6$)-$\beta$-D-glucoside [rutin, 3], quercetin-3-O-$\beta$-D-glucoside [isoquercitrin, 2] and kaempferol-3-O-$\beta$-D-glucoside [astragalin, 1]. These compounds were identified based on interpretation of their physical, chemical, and spectral data. Moreover, the spectrophotometric estimation of the flavonoids content revealed that the aerial parts of the plant contain an appreciable amount of flavonoids (0.89%) calculated as rutin. The data obtained from this study revealed that the flavonol glycosides of F-2 protect the rat liver from hepatic damage induced by $CCl_4$ through inhibition of lipid peroxidation caused by $CCl_4$ reactive free radicals.