• BMB Reports
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• v.32 no.3
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• pp.232-238
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• 1999

Sex differences in the induction of microsomal cytochrome P-450 (CYP) and the activities of several related enzymes of Sprague-Dawley rats treated with 1-bromopropane (1-BrP) were investigated. Male and female rats were exposed to 50, 300, and 1800 ppm of 1-BrP per kg body weight (6 h a day,S days a week, 8 weeks) by inhalation. The mean body weight of 1-BrP treated groups increased according to the day elapsed, but four and five weeks respectively after the start of the exposure, the mean body weight of male and female rats had significantly reduced in the group treated with 1800 ppm 1-BrP compared with the control group (p<0.01). While the relative weights of liver increased in both sexes, statistical significance in both sexes was found only in the group receiving 1800 ppm/kg of 1-BrP (p<0.01). The total contents of CYP, $b_5$, NADPH-P-450 reductase, NADH $b_5$ reductase, ethoxyresorufin-O-deethylase (EROD), pentoxyresorufin-O-dealkylase (PROD), and p-nitrophenol hydroxylase (pNPH) activities were examined for the possible effects of 1-BrP. No significant changes in the CYP and $b_5$ contents, NADPH-P-450 reuctase, NADH $b_5$ reductase, ethoxyresorufin-O-deethylase (EROD), and pentoxyresorufin- O-dealkylase (PROD) were observed between the control and treated groups. The activity of pNPH increased steadily with the increase in the concentration of 1-BrP in both sexes, but was significantly increased only in the 1800 ppm-treated group of male rats (p<0.05). When Western blottings were carried out with three monoclonal antibodies (MAb 1-7-1, MAb 2-66-3, and MAb 1-98-1) which were specific against CYP1A1/2, CYP2B1/2, and CYP2E1, respectively, a strong signal corresponding to CYP2E1 was observed in microsomes obtained from rats treated with 1-BrP. Glutathione S-transferase (GST) activity and the content of lipid peroxide significantly increased in the treated groups compared with the control group (p<0.05). These results suggest that 1-BrP can primarily induce CYP2E1 as the major form and that GST phase II enzymes play important roles in 1-BrP metabolism, showing sex-dependence in the metabolic mechanism of 1-BrP in the rat liver.

• BMB Reports
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• v.42 no.4
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• pp.232-237
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• 2009

Sterol regulatory element-binding protein (SREBP)-1c plays a crucial role in the regulation of lipogenic enzymes in the liver. We previously reported that an X-chromosome-linked RNA binding motif (RBMX) regulates the promoter activity of Srebp-1c. However, still unknown was how it regulates the gene expression. To elucidate this mechanism, we screened the cDNA library from mouse liver by yeast two-hybrid assay using RBMX as bait and identified scaffold attachment factor B1 (SAFB1). Immunoprecipitation assay demonstrated binding of SAFB1 to RBMX. Chromatin immunoprecipitation assay showed binding of both SAFB1 and RBMX to the upstream region of Srebp-1c gene. RNA interference of Safb1 reduced the basal and RBMX-induced Srebp-1c promoter activities, resulting in reduced Srebp-1c gene expression. The effect of SAFB1 overexpression on Srebp-1c promoter was found only in the presence of RBMX. These results indicate a major role for SAFB1 in the activation of Srebp-1c through its interaction with RBMX.

• Journal of Life Science
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• v.25 no.9
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• pp.1014-1020
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• 2015

This study suggests that fermented rice bran extract contains natural antioxidants. The contents of bioactive materials (e.g., polyphenolic compounds and flavonoids), antioxidative properties (DPPH (α,α'- diphenyl-β-picrylhydrazyl) free radical scavenging activity, Fe reducing, Cu reducing power, peroxidation of linoleic acid and rat hepatocyte microsome) were tested by in vitro experimental models using fermented rice bran (FRB) extract. The concentrations of phenolic compound and flavonoid were 19.92 mg/g and 11.56 mg/g, respectively. In oxidation in vitro models using DPPH free radical scavenging activity, (free radical scavenging activity 69.8%) Fe reducing power and Cu reducing power (effect of dose-dependent manner), Fe²⁺/ascorbate induced linolenic acid peroxidation by ferric thiocyanate and thiobarbituric acid (TBA) methods (inhibition activity 81%), and autooxidation of rat hepatic microsomes membrane (lipid peroxidation inhibition activity 38%), antioxidative activities were stronger in FRB extract than FRS (Fermented Rice and Soybean, positive control) extract and, these effects were dose-dependent manner. From these results, FRB extract was shown to have the most potent antioxidative properties and contain the highest amounts of antioxidative compounds such as phenolic compounds and flavonoids. Overall, these results may provide the basic data to understand the antioxidative properties of fermented rice bran for development of functional foods.

• Journal of Veterinary Clinics
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• v.8 no.2
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• pp.127-142
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• 1991

This study was carried out to investigate fatty liver in Korean black goats. Adult female goats were divided into 3 test groups(A, B and C). Group A and B of goats each received 3 test consecutive daily doses of DL-ethionine at 75mg/kg and 150mg/kg body weight, respectively. Group C of goats was given 3 consecutive doses of the compound every 48 hours at 150mg/kg body weight. The clinical symptoms, hematological values, serum chemical values and histopathological study of the liver were investigated in the test animals. The results obtained are as follows ; 1. Fatty liver were observed in every test animal. 2. Some clinical symptoms( anorexia, depression) were appeared from 1st day to 7th day after administration of the compound in every test animal. In addition to these symptoms, diarrhea and salivation were generally observed in test animals which were given the compound at 150mg/kg body weight. The degree of these symptoms was dose dependent. 3. There was no significant variations in total WBC counts and fibrinogen values in the blood of test goats. The PCV values were significantly increased on 5th day of dosing in group A and B of goats. 4. The total lipid value was not changed but the concentration of NEFA was significantly increased on 3rd day of dosing with the compound and returned to normal value after 10 days hereafter. The value of triglycerides was significantly increased on 1st day and returned to normal value on 3rd day of dosing. The value of cholesterol was significantly decreased on 3rd day and returned to normal value on 10th day after treatment. 5. Total protein level was decreased on 10th day of dosing in the groups of B and C, and billirubin level was significantly increased on 7th day of dosing in every test group and returned to normal level after 13th day of administration. 6. The activity of GGT in serum was not changed while the activities of SDH and AST were significantly increased in every test goat and those values were returned to normal after 10~13th day of trestment. 7 The 35K-protein fraction in serum was not detected by SDS-polyacrylamide gel electrophoresis, but this protein fraction was detected by the same method after treating the 21st and 22nd fraction which were obtained by column chromatography with Sephadex G-100. 8. The affected liver was congested and swollen on 3rd day, and yellowish brown in color and mottled appearance on 7th day of treatment. Histopathologically, fat droplets were common in the hepatocytes, this change was intensive on 7th day after treatment in group B and C. Hepatic cell necrosis was observed in some livers but this pathological change was disappeared and returned to normal after 13 days of treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.683-687
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• 2015

Aloe vera gel exhibits protective effects against insulin resistance as well as lipid-lowering and anti-diabetic effects. The anti-diabetic compounds in this gel were identified as Aloe-sterols. Aloe vera gel extract (AVGE) containing Aloe-sterols has recently been produced using a new procedure. We previously reported that AVGE reduced large-sized intestinal polyps in Apc-deficient Min mice fed a high fat diet (HFD), suggesting that Aloe vera gel may protect against colorectal cancer. In the present study, we examined the effects of Aloe vera gel powder (AVGP) and AVGE on azoxymethane-induced colorectal preneoplastic aberrant crypt foci (ACF) in mice fed a HFD. Male C57BL/6J mice were given a normal diet (ND), HFD, HFD containing 0.5% carboxymethyl cellulose solution, which was used as a solvent for AVGE (HFDC), HFD containing 3% or 1% AVGP, and HFDC containing 0.0125% (H-) or 0.00375% (L-) AVGE. The number of ACF was significantly lower in mice given 3% AVGP and H-AVGE than in those given HFD or HFDC alone. Moreover, 3% AVGP, H-AVGE and L-AVGE significantly decreased the mean Ki-67 labeling index, assessed as a measure of cell proliferation in the colonic mucosa. In addition, hepatic phase II enzyme glutathione S-transferase mRNA levels were higher in the H-AVGE group than in the HFDC group. These results suggest that both AVGP and AVGE may have chemopreventive effects on colorectal carcinogenesis under the HFD condition. Furthermore, the concentration of Aloe-sterols was similar between 3% AVGP and H-AVGE, suggesting that Aloe-sterols were the main active ingredients in this experiment.

• Journal of Life Science
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• v.28 no.1
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• pp.58-67
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• 2018

This study aimed to identify the effects of extracts of fermented Angelica gigas Nakai (A. gigas) with a Monascus purpureus strain on anti-obesity in a high-fat diet (HFD)-induced obesity rat model. Male Sprague-Dawley rats were randomly divided into seven dietary groups (n=8 per group), as follows: a normal diet group (N) and six HFD groups (C: control, HFD and no treatment; AG: HFD +10% A. gigas extracts; FAG2.5: HFD +2.5% fermented A. gigas extracts; FAG5: HFD +5% fermented A. gigas extracts; FAG10: HFD +10% fermented A. gigas extracts; GC: HFD + Garcinia cambogia extracts). FAG-fed rats exhibited effectively lowered rates of increasing body weight and visceral fat accumulation in the HFD-induced obesity model. The activities of several hepatic marker enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP), were increased with HFD-induced obesity, but levels of these marker enzymes were significantly decreased in FAG-fed rats. The consumption of FAG reduced triglyceride concentrations in serum to normal levels. FAG-fed rats showed effectively increased leptin concentrations in the HFD-induced obesity model. HFD ingestion induced a significant increase in the thiobarbituric acid reactive substances (TBARS) levels, which was decreased in FAG-fed rats. Hematoxylin and eosin staining and Oil Red O staining of the liver showed that the lipid deposits were decreased via FAG feeding. Moreover, hematoxylin and eosin staining of epididymal adipose adipose tissue showed that the adipocyte were decreased by feeding FAG.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.5917-5935
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• 2012

Background: Hepatitis C virus (HCV) causes acute and chronic human hepatitis infection and as such is an important global health problem. The virus was discovered in the USA in 1989 and it is now known that three to four million people are infected every year, WHO estimating that 3 percent of the 7 billion people worldwide being chronically infected. Humans are the natural hosts of HCV and this virus can eventually lead to permanent liver damage and carcinoma. HCV is a member of the Flaviviridae family and Hepacivirus genus. The diameter of the virus is about 50-60 nm and the virion contains a single-stranded positive RNA approximately 10,000 nucleotides in length and consisting of one ORF which is encapsulated by an external lipid envelope and icosahedral capsid. HCV is a heterogeneous virus, classified into 6 genotypes and more than 50 subtypes. Because of the genome variability, nucleotide sequences of genotypes differ by approximately 31-34%, and by 20-23% among subtypes. Quasi-species of mixed virus populations provide a survival advantage for the virus to create multiple variant genomes and a high rate of generation of variants to allow rapid selection of mutants for new environmental conditions. Direct contact with infected blood and blood products, sexual relationships and availability of injectable drugs have had remarkable effects on HCV epidemiology. Hundreds of thousands of people die each year from hepatitis and liver cancer caused by HCV virus infection. Approximately 80% of patients with acute hepatitis C progress into a chronic disease state leading to serious hepatic disorders, 10-20% of which develop chronic liver cirrhosis and hepatocellular carcinoma. The incubation period of HCV is 6-8 weeks and the infection is often asymptomatic so it is very hard to detect at early stages, making early treatment very difficult. Therefore, hepatitis C is called a "silent disease". Neutralizing antibodies are produced against several HCV proteins during infection but the virus mutates to escape from antibodies. Some patients with chronic hepatitis C may have some symptoms such as fatigue, muscle aches, nausea and pain. Autoimmune and immunecomplex-mediated diseases have also been reported with chronic HCV infection.

• Preventive Nutrition and Food Science
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• v.15 no.2
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• pp.83-87
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• 2010

The cholesterol-lowering effects of soymilk fermented with Bacillus subtilis KCCM42923 were studied in apolipoprotein E knockout (ApoE KO) mice and compared to the cholesterol-lowering effects of soymilk to which cheonggukjang powder had been added. ApoE KO mice were divided into 3 groups (n=7/group). Animals were fed either an atherogenic diet only (AD, control group), an AD supplemented with fermented soymilk containing Corni fructus (FSM group), or an AD supplemented with soymik to which cheonggukjang (CGJ) powder had been added at 5% (w/v) (CPS group) for 8 weeks. The amount of FSM or CPS supplementing the AD was 20.8 mL/kg BW. There were no differences in either body weight gain or organ weights among three groups. In the FSM group, the concentration of plasma total cholesterol (TC) and LDL cholesterol (LDLC) were significantly decreased by 26.2% and 30.3% compared with the values of the control group (p<0.05). However, the triglyceride (TG) and HDL-cholesterol (HDLC) levels were not affected. These beneficial effects of FSM on suppressing the increase in plasma cholesterol level by AD were greater than those of CPS, which revealed 15.4% and 16.4% inhibition for TC and LDLC, respectively. However, these differences between FSM and CPS groups were not significantly different. A preventative effect of FSM or CPS on the accumulation of hepatic TC, but not on TG, was observed. FSM and CPS did not demonstrate any effects on fecal lipid excretion. In conclusion, the cholesterol-lowering effects of the soymilk fermented with Bacillus subtilis KCCM42923 were comparable to CGJ powder-added soymilk. These results suggest that drinking FSM might provide beneficial effects on controlling plasma cholesterol levels.

• Journal of Nutrition and Health
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• v.25 no.7
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• pp.555-568
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• 1992

This study was to compare the effects of dietary n-6 and n-3 fatty acids and fat unsaturation on plasma lipids and chemical composition of VLDL and LDL fraction and lipogenic enzymes activity in rat liver under the conditions providing 1) a similar amount of n-6, n-3 fatty acids(LA, ALA, EPA+DHA) in diets and 2) the various degree of fat unsaturation. Male Sprague-Dawley rats weighing 420g were treated for 6-n with six experimental diets providing 25% of energy as fat and which were different only in fatty acid composition. The fats used for a source of each fatty acid were beet tallow for saturated fatty acid corn oil for n-6 linoleic acid(LA) perilla oil for n-3 $\alpha$-linolenic acid(ALA) and fish oil n-3 eicosapentaenoic acid (EPA) and n-3 docosahexaenoic acid(DHA). Plasma cholesterol level was increased by corn oil to compare with beef tallow but was decreased by perilla oil or fish oil. Plasma TG level was significantly decreased by perilla oil or fish oil. Fish oil significantly reduced the level of HDL-Chol and the proportion of Chol in LDL fraction and that of TG in vVLDL fraction. Overall there was a singificant negative correlation between the level of each plasma lipid(Chol TG, VLDL-TG, LDL-C) and the degree of fat unsaturation. However this rerlationship is not always true when compared the hypolipidemic effect of each fatty acid at a similar level of fat unsaturation. There was a trend such taht glucose 6-P dehydrogenase 6-phosphogluconate dehydrogenase and malic enzyme activites were reduced by n-3 fatty acids. Perilla oil significantly increased the incorporation of c20:5 and c22:5 into liver tissue and fish oil suignificantly increased the incorporation of c20:5, c22:6 into liver tissue and the effect of long chain n-3 fatty acid incorporation was greater by fish oil. therefore the hypotriglyceridemic effect of n-3 fatty acid could be resulted from the interference of hepatic lipogenesis by long-chain n-3 fatty acids and the reduced proportion of TG in VLDL fraction and its effect was greater by n-3 EPA+DHA than n-3 ALA even though plasma Chol and TG levels were also influenced by the degree of dietary fat unsaturation.

• Asian-Australasian Journal of Animal Sciences
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• v.27 no.6
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• pp.907-915
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• 2014

Alpha-lipoic acid (${\alpha}$-LA) is not only involved in energy metabolism, but is also a powerful antioxidant that can protect against hepatic oxidative stress induced by some drugs, toxins, or under various physiological and pathophysiological conditions. Here, we investigated the effect of ${\alpha}$-LA against liver oxidative damage in broilers exposed to aflatoxin $B_1$ ($AFB_1$). Birds were randomly divided into four groups and assigned different diets: basal diet, 300 mg/kg ${\alpha}$-LA supplementation in basal diet, diet containing 74 ${\mu}g/kg$ $AFB_1$, and 300 mg/kg ${\alpha}$-LA supplementation in diet containing 74 ${\mu}g/kg$ $AFB_1$, for 3 weeks. The results revealed that the addition of 300 mg/kg ${\alpha}$-LA protected against the liver function damage of broilers induced by chronic low dose of $AFB_1$ as estimated by a significant (p<0.05) change in levels of plasma total protein, albumin, alkaline phosphatase and the activities of liver glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase. The histopathological analysis also showed that liver tissues were injured in the $AFB_1$ diet, but this effect was alleviated by the addition of 300 mg/kg ${\alpha}$-LA. Additionally, $AFB_1$ induced a profound elevation of oxidative stress in birds, as indicated by an increase in malondialdehyde level, a decrease in glutathione peroxidase activity and a depletion of the glutathione content in the liver. All of these negative effects were inhibited by treatment with ${\alpha}$-LA. Our results suggest that the inhibition of $AFB_1$-induced excess production of lipid peroxides and the maintenance of intracellular antioxidant status may play important roles in the protective effects of ${\alpha}$-LA against $AFB_1$-induced oxidative damage in the liver.