• Toxicological Research
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• v.11 no.2
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• pp.267-271
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• 1995

A single large dose of ethanol as well as chronic ethanol consumption produces alcoholic fatty liver in human and experimental animals. We examined the effects of YH439, a potential hepatoprotective agent, on alcoholic fatty liver generation in adult female rats. In rats treated with YH439 (250 mg/kg, po) 4 hr prior to a single dose of ethanol (6 g/kg, po), a significant decrease in hepatic triglyceride accumulation was observed. YH439 also has an inhibitory effect on hepatic triglyceride and cholesterol accumulation induced by repeated ethanol treatments for one week. Because it has been known that induction of alcoholic fatty liver is associated with lipid peroxidation and/or hepatic glutathione depression, the effect of YH439 on these parameters was determined in the livers of rats treated with ethanol. Coadministration with YH439 inhibited MDA formation and gIutathione depression induced by acute or repeated ethanol administration. In order to determine the effect of YH439 on ethanol metabolism in vivo, disappearance of ethanol from blood was measured. In rats treated with a single dose of ethanol (6 g/kg, po), the ethanol concentration in blood reached a peak approximately 120 min following the treatment which declined linearly for 18 hrs. YH439 had no effect on the decline of blood ethanol concentration regardless of the dose of ethanol given to rats. These results in this study suggest that YH439 has an inhibitory effect on fatty liver generation induced by acute or repeated ethanol consumption through a mechanism not directly related to the rate of ethanol metabolism in vivo.

• Journal of the Korean Society of Food Science and Nutrition
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• v.25 no.3
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• pp.392-398
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• 1996

This study was carried out to determine the effects of sodium alginate and cellulose on the cholesterol metabolism in cholesterol-fed rats. Thirty male Sprague-Dawley rats were randomly assigned to three dietary treatments. Rats were fed, ad libitum, diets containing 10% dietary fibers as sodium alginate, cellulose or fiber-free with 1% cholesterol for 4 weeks. The results obtained were as follows: the feeding of sodium alginate with 1% cholesterol induced a significant decrease in plasma cholesterol and TG. The feeding of sodium alginate significantly decreased hepatic total lipids and TG levels, whereas the feeding of sodium alginate significantly increased hepatic HMG-CoA reductase activity. The feeding of sodium alginate and cellulose significantly increased fecal cholesterol and bile acid excretion. The excretion of TG in sodium alginate group, however, was two-fold and four-fold increased compared to cellulose and fiber-free group, respectively. As a result of this study, the ingestion of sodium alginate decreased plasma cholesterol and TG concentrations and liver TG concentration. This may be explained by the facts that fecal cholesterol, bile acid and TG level were increased significantly in sodium alginate group. The increased hepatic HMG-CoA reductase activity by sodium alginate feeding appears to be corresponded to whole-body cholesterol homeostasis.

• Biomedical Science Letters
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• v.17 no.1
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• pp.13-20
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• 2011

The peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) is a nuclear transcription factor that plays a central role in lipid and lipoprotein metabolism. To investigate whether swim training improves obesity and lipid metabolism through $PPAR{\alpha}$ activation in female sham-operated (Sham) and ovariectomized (OVX) mice, we measured body weight, visceral adipose tissue mass, serum free fatty acid at 6 weeks as well as the expression of hepatic $PPAR{\alpha}$ target genes involved in fatty acid oxidation. Swim-trained mice had decreased body weight, visceral adipose tissue mass and serum free fatty acid levels compared to high fat diet fed control mice in both female Sham and OVX mice. These reductions were more prominent in OVX than in Sham mice. Swim training significantly increased hepatic mRNA levels of $PPAR{\alpha}$ target genes responsible for mitochondrial fatty acid ${\beta}$-oxidation, such as carnitine palmitoyltransgerase-1 (CPT-1), very long chain acyl-CoA dehydrogenase (VLCAD), and medium chain acyl-CoA dehydrogenase (MCAD) in OVX mice. However, swim trained female Sham mice did not increase hepatic mRNA levels of $PPAR{\alpha}$ target genes responsible for mitochondrial fatty acid ${\beta}$-oxidation compared to Sham control mice. These results indicate that swim training differentially regulates body weight and adipose tissue mass between OVX and Sham mice, at least in part due to differences in liver $PPAR{\alpha}$ activation.

• Toxicological Research
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• v.35 no.4
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• pp.403-410
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• 2019

Curcumin, a hydrophobic polyphenol isolated from the Curcuma longa L. plant, has many pharmacological properties, including antioxidant, anti-inflammatory, and chemo-preventive activities. Curcumin has been shown to have potential in preventing nonalcoholic fatty liver disease (NAFLD). However, the low bioavailability of curcumin has proven to be a major limiting factor in its clinical adoption. Theracurmin, a highly bioavailable curcumin that utilizes micronized technology showed improved biological absorbability in vivo. The aim of this study was to investigate the role of theracurmin in modulating hepatic lipid metabolism in vivo. A fatty liver mouse model was produced by feeding mice a high fat diet (HFD; 60% fat) for 12 weeks. We found that treatment for 12 weeks with theracurmin significantly lowered plasma triacylglycerol (TG) levels and reduced HFD-induced liver fat accumulation. Theracurmin treatment lowered hepatic TG and total cholesterol (T-CHO) levels in HFD-fed mice compared to controls. In addition, theracurmin administration significantly reduced lipid peroxidation and cellular damage caused by reactive oxygen species in HFD-fed mice. Overall, these results suggest that theracurmin has the ability to control lipid metabolism and can potentially serve as an effective therapeutic remedy for the prevention of fatty liver.

• Journal of Nutrition and Health
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• v.38 no.9
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• pp.689-697
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• 2005

This study was conducted to fine out the preventive effects of chitosan and chitosan oligomer on the disorders of hepatic functions and lipid metabolism induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) using adult male rats (SD) for four weeks. Rats were fed chitosan ($4\%$) or chitosan oligomer ($4\%$) diets respectively before 3weeks of TCDD treatment (50 ug/kg BW) by intraperitoneal injection and then continually supplied these diets for one week until being sacrificed. The elevation of serum total and LDL cholesterol levels induced by TCDD treatment was significantly reduced in the rats fed chitosan diets. The increment of liver triglyceride levels caused by TCDD treatment was tended to suppress in all rats fed chitosan and chitosan oligomer diets. Fecal total lipid and cholesterol excretion were high levels in the rats fed chitosan diets. The hepatic cytosolic catalase activities significantly decreased by TCDD treatment appeared recovering trend by chitosan diets. In hepatic microsomal cytochrome p-450, NADPH cytochrome p-450 reductase, ethoxycoumarin-o-deethylase (ECOD) and benzphetamin N-demethylase (BPND) chitosan than chitosan oligomer diets apparently decreased the increasing levels by TCDD treatment. In histochemical observation the fat droplets and apoptosis of hepatocytes by TCDD treatment were markedly alleviated by chitosan and chitosan oligomer diets. These results indicate that chitosan, more than chitosan oligomer can exert preventive effects on some disorders of hepatic functions and lipids accumulation by TCDD.

• Journal of Nutrition and Health
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• v.38 no.4
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• pp.267-278
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• 2005

Postmenopausal women or ovariectomized rats are associated with increased cholesterol levels, which are risk factors of metabolic syndrome and cardiovascular diseases. Increased prevalence of metabolic syndrome after menopause might be associated with estradiol deficiency. Harmful effect of estradiol hampers the casual usage of hormone to prevent the metabolic syndrome. Soy protein has been reported to show several beneficial effects on health, however it is unclear which components of soy protein is responsible for anti-obesity and hypocholesterolemic effects. Soy isoflavones, gem-stein and daizein, are suggested to have anti-obesity and hypocholesterolemic effects but with inconsistency. The present study investigated the effect of supplementation of genistein (experiment I) and soy protein containing isoflavones (experiment II) to high fat diet on body weight gain, food intake, liver and fat tissue weight and the lipid levels in ovariectomized rats. Plasma and hepatic lipid contents and the mRNA levels of genes encoding lipid metabolism related proteins, such as CPT1 and HMGR were measured. Ovariectomy increased body weight, fat tissue weight and plasma and hepatic lipid levels which increase the risk of metabolic syndrome. Soy protein could improve plasma and hepatic lipids levels. Soy protein also increased hepatic CPT1 and HMGR mRNA levels. Plasma and hepatic lipids levels could not be decreased by dietary genistein alone. In contrast, lipids levels could be decreased by isoflavone-fortified soy protein, suggesting that the ingestion of soy protein enriched with isoflavone gives more benefit for protecting postmenopausal women from metabolic syndrome.

• Journal of Pharmaceutical Investigation
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• v.28 no.2
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• pp.73-80
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• 1998

In order to elucidate the effect of N-demethylation on the in vivo metabolite kinetics, especially hepatic first-pass effect of trimebutine(TMB), the N-demethylation of TMB to N-monodesmethyl trimebutine(N-TMB) was studied in rats. TMB(10 mg/kg) and N-TMB(10 mg/kg) were injected into the femoral and the portal vein, respectively. And the pharmacokinetic parameters were obtained from the plasma concentration-time profiles of TMB and N-TMB determined by the simultaneous analysis using high-performance liquid chromatography. It was supposed that these drugs were almost metabolized in vivo because the urinary and biliary excreated amounts of TMB and N-TMB were lower than 0.1% of the administered dose. According to the hepatic biotransformation model and metabolic pathways of TMB proposed, it was found that the fraction of systemic clearance of TMB which formed N-TMB in liver$(G_{mi})$ was 0.826, that of TMB which furnishes the available N-TMB to the systemic circulation$(F_{mi})$ was 0.083, and the absolute hepatic bioavailability of N-TMB formed trom TMB$(F_{mi.p})$ was 0.1. These results showed that TMB was suspected of the sequential hepatic first-pass metabolism and N-demethylated by 82.6%. Therefore, the residue would be hydrolyzed by the esterase in the liver. That is, the ability of N-demethylation of TMB was 4.75-fold larger than that of hydrolysis by the esterase in rats.

• Nutritional Sciences
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• v.9 no.4
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• pp.259-266
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• 2006

The current study examined the effect of quercetin supplements on the lipid-lowering and antioxidant metabolism in ethanol-fed rats. The control $group(E_8)$ received ethanol only diet for 8 wks, whereas the other group$(E_8Q_4)$ received a diet including quercetin supplementation(0.05% wt/wt) for 4 wks while on the ethanol diet for 8wks. The hepatic alcohol dehydrogenase activity was significantly higher in the $E_8Q_4$ group than in the $E_8$ group. Supplementation with quercetin significantly elevated the HDL- cholesterol concentration, the HDL-C/total-C ratio, and lowered the atherogenic index(AI) compared to the $E_8$ group. The hepatic triglyceride and cholesterol contents were significantly lowered by the quercetin supplement compared to those of the control group. The hepatic HMG-CoA reductase and ACAT activities of the $E_8Q_4$ group were significantly lower than those of the $E_8$ group. The overall potential for antioxidant defense was significantly enhanced by the quercetin supplement, as indicated by a decrease in plasma and hepatic TBARS levels. The hepatic GSH-Px and G6PD activities were significantly higher in the $E_8Q_4$ group compared to the $E_8$ group. The current results suggest that dietary quercetin leads to the inhibition of HMG-CoA reductase and ACAT, which in turn lowers cholesterol levels and normalizes antioxidant enzyme activities.

• Journal of the East Asian Society of Dietary Life
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• v.1 no.3
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• pp.299-304
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• 1991

In this study the effects of water extracts of endocarps and seeds of omija(Schizandra chinensis Baillon)on alcohol metabolism in rats were investigated. 25% alcoholic solution(v/v,0.75g/200g B.W.)and 40% alcoholic solution(v/v,0.80g/200g B.W.)were orally administered to rats for 2 hours. The levels of metabolites and enzyme activities both on serum and liver were not changed by acute oral adminiatration of 25% and 40% alcoholic solution. Blood alcohol levels were significantly lowered by treatment of water extracts of endocarps and seeds of omija in rats administered with 25% and 40% alcohol. In 25% alcohol treated group, serum GPT level was decreased but hepatic G-6-P DH and pyruvate levels were increased. In 40% alcohol treated group, water extracts of endocarps and seeds of omija resulted in a significant decreased in serum levels of FFA, GPT but increased in serum glucose level. Hepatic levels of cytosolic protein, glycogen and pyruvate were increased by water extracts of omija parts in 40% alcohol treated group.

• Biomedical Science Letters
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• v.13 no.2
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• pp.99-104
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• 2007

To determine whether 17$\beta$-estradiol induces the morphological changes in adipose and liver tissues, we measured the effects of 17$\beta$-estradiol on adipose tissue mass, adipocyte histology and hepatic lipid accumulation in female ovariectomized (OVX) C57BL/6J mice. Compared to vehicle-treated control mice, 17$\beta$-estradiol-treated mice decreased adipose tissue mass and the size of adipocytes, and concomitantly increased the number of adipocytes in a dose-dependent manner. In addition, the administration of 17$\beta$-estradiol resulted in reduced hepatic lipid accumulation in a dose-dependent manner. These results suggest that estrogen may regulate adipocyte development and lipid metabolism in female OVX C57BL/6J mice.