• Archives of Pharmacal Research
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• 제15권1호
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• pp.78-86
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• 1992

The induction of hepatic cytochromes P450 and metabolic effects have been examined in male and female Sprague-Dawley rats following treatment with either phenobarbital or 3-methylcholanthrene. Hepatic cytochrome P450 levels were higher in males than in females by ~40%. Treatment of male and female rats with phenobarbital or 3-methylcholanthrene resulted in an ~1.6 and 2-fold increase, respectively, in heptic microsomal cytochrome P450 levels in both sexes, relative to untreated animals. Immunoblot analyses were performed to compare sex-related changes in P450 levels. Hepatic P45IIB1 levels in males were greater than those in females following phenobarbital treatment. 3-Methylcholanthrene-induced male hepatic microsomes exhibited greater levels of P450 females failed to exhibit a band. Mab PCN 2-13-1 against P-45-IIIA recognized an intense in uninduced microsomes from female rats. The levels of P450IIIA in males were increased 2 to 3-fold following treatment with phenobarbital, while the increase of IIIA levels in females by phenobarbital was minimal, as monitored by immunoblot analysis. Solid phase radiommunoassay using monoclonal antibodies supported the results of immunoblot analysis. Phenobarbital treatment caused a 6.5-fold increase in the monoclonal iantibody binding to IIBI in males, whereas treatment of females with phenobarbital resulted of IA levels by 3-methylcholanthrene was also greater in females than in males (10-vs. 8-fold) although the levels of induced IA were comparable inboth sexes, as assessed by radiommunoassay. Radioimmunoassay also showed that hepatic IIEI level was 1.5-fold higher in males than in females and that either phenobarbital or 3-methylcholanthrene treatment caused 80% to 40% decrease in IIEL levels, relative to control, in both sexes. Sex-related metabolic activities were examined in hepatic microsomes. Hexobarbital hydroxylase activity was 2-to 3-fold higher in uninduced microsomes from males than that from females. This hydroxylase activity was increased 2-and 3-fold in males and females, respectively, following phenobarbital treatment, as compared to controls. Addition females produced 64% and 84% inhibition of hexobarbital oxidation, respectively. Aryl hydrocarbon hydroxylase activity was increased -12 and 26-fold in males and females respectively. Following phenobarbital treatment, as compared to controls. Addition of anti-P450IIB1 antibody to phenobarbital-induced hepatic microsomes from males and females produced 64% and 84% inhibition of hexobarbital oxidation, respectively. Aryl hydrocarbon hydroxylase activity was increased -12 and 26 fold in males and females, respectively, following 3-methylcholanthrene treatment relative to controls. The anti-P-450IA antibody inhibitable rate of aryl hydrocarbon hydroxylase activity was comparable in both sexes following 3-methylcholanthrene treatment relative to controls. The anti-P450LA antibody inhibitable rate of aryl hydrocarbon hydroxylase activity was comparable in both sexes following 3-methylcholanthrene treatment (-70%). These results demonstrate that levels of hepatic P450IIB1 or P450IA are greater in male than in female for untreated, phenobarbital-or-3-methylcholanthrene treated rats. In addition, the relative for untreated phenobarbital-or 3-methylcholanthrene treated rats. In addition, the relative increase of phenobarbital-or 3-methylcholanthrene treated rats. In addition, the relative increase of phenobarbital-or 3-methylcholanthrene treated rats. In addition, the relative increase of P450IIB1 or IA phenobarbital or 3-methylcholanthrene is more significant in females.

• Journal of Nutrition and Health
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• 제33권2호
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• pp.124-133
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• 2000

This study evaluated the effects of chronic ethanol consumption and/or taurine supplementation on hepatic total, phospholipid fatty acid composition and the metabolism of rats fed one of three purified liquid diets for 8 weeks. the rats followed either the control diet (CD, ethanol-free and taurine-free diet); ethanol diet (ED, CD+ 50g ethanol/L) or ethanol-taurine diet (ETD, ED+3.75g taurne/L). Chronic ethanol consumption and/or dietary taurine supplementation were associated with altered hepatic total and phospholipid fatty acid composition. compared to the values for the control rats, ED or ETD significantly decreased the percentage of total monounsaturated fatty acids ($\Sigma$MUFA), and increased the percentage of total polyunsaturated fatty acids ($\Sigma$PUFA) of hepatic total lipids(p〈0.01). Percentages of 14:0(P〈0.01) and 16:0(p〈0.001) were sigificantly lower, and those of 18:0(p〈0.01), 20:0(p〈0.001), 20:3$\omega$6(p〈0.01) and 22:4$\omega$6(p〈0.01) in hepatic total fatty acid compositions were oserved in rats fed ETD versus those fed ED or ETD. No significant differences in hepatic total fatty acid compositions were observed in rats fed ETD versus those fed ED. Percentages of 24:0(p〈0.01), 16:1(p〈0.05), 20:1(p〈0.01), 18:2$\omega$6(p〈0.01) and 18:3$\omega$3(p〈0.05) in hepati phospholipids were significantly higher, and those of 14:0(p〈0.01), 16:0(p〈0.001), 20:3$\omega$3(p〈0.05) in hepatic phospholipids were significantly higher, and those of 14:0(p〈0.01), 16:0(p〈0.001), 20:3$\omega$3(p〈0.001), 22:6$\omega$3(p〈0.001) and $\Sigma$$\omega$3(P〈0.001) were significantly lower in rats fed ED or ETD compared to the values for the control rats. The Δ5 desaturation index(20:3$\omega$6⇒20:4$\omega$6) and elongation index (20:5$\omega$3⇒22:5$\omega$3) of hepatic phospholipid index (20:3$\omega$6⇒20:4$\omega$6) and decreased Δ4 desaturation index (22:5$\omega$3⇒22:6$\omega$3) compared to the values for the ED rats. These changes in hepatic fatty acid composition induced by chronic ethanol consumption and/or taurine supplementation might be associated with the modulations of physical properties of the hepatic cell membrane and its sensitivity to peroxidation damage.

• The Korean Journal of Physiology and Pharmacology
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• 제18권4호
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• pp.333-339
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• 2014

Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been known to reverse hepatic steatosis in ob/ob mice. Although many studies have evaluated molecular targets of Ex-4, its mechanism of action on hepatic steatosis and fibrosis has not fully been determined. In the liver, glucose transporter 4 (GLUT4) is mainly expressed in hepatocytes, endothelial cells and hepatic stellate cells (HSCs). In the present study, the effects of Ex-4 on GLUT4 expression were determined in the liver of ob/ob mice. Ob/ob mice were treated with Ex-4 for 10 weeks. Serum metabolic parameters, hepatic triglyceride levels, and liver tissues were evaluated for hepatic steatosis. The weights of the whole body and liver in ob/ob mice were reduced by long-term Ex-4 treatment. Serum metabolic parameters, hepatic steatosis, and hepatic fibrosis in ob/ob mice were reduced by Ex-4. Particularly, Ex-4 improved hepatic steatosis by enhancing GLUT4 via GLP-1R activation in ob/ob mice. Ex-4 treatment also inhibited hepatic fibrosis by decreasing expression of connective tissue growth factor in HSCs of ob/ob mice. Our data suggest that GLP-1 agonists exert a protective effect on hepatic steatosis and fibrosis in obesity and type 2 diabetes.

• Nutrition Research and Practice
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• 제14권6호
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• pp.568-579
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• 2020

BACKGROUD/OBJECTIVES: Hepatic steatosis is the most common liver disorder, particularly in postmenopausal women. This study investigated the protective effects of standardized rice bran extract (RBS) on ovariectomized (OVX)-induced hepatic steatosis in rats. MATERIALS/METHODS: HepG2 cells were incubated with 200 µM oleic acid to induce lipid accumulation with or without RBS and γ-oryzanol. OVX rats were separated into three groups and fed a normal diet (ND) or the ND containing 17β-estradiol (E2; 10 ㎍/kg) and RBS (500 mg/kg) for 16 weeks. RESULTS: RBS supplementation improved serum triglyceride and free fatty acid levels in OVX rats. Histological analysis showed that RBS significantly attenuated hepatic fat accumulation and decreased hepatic lipid, total cholesterol, and triglyceride levels. Additionally, RBS suppressed the estrogen deficiency-induced upregulation of lipogenic genes, such as sterol regulatory element-binding protein 1 (SREBP1), acetyl-CoA carboxylase 1, fatty acid synthase, glycerol-3-phosphate acyltransferase, and stearoyl-CoA desaturase 1. CONCLUSIONS: RBS and γ-oryzanol effectively reduced lipid accumulation in a HepG2 cell hepatic steatosis model. RBS improves OVX-induced hepatic steatosis by regulating the SREBP1-mediated activation of lipogenic genes, suggesting the benefits of RBS in preventing fatty liver in postmenopausal women.

• 대한의생명과학회지
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• 제23권2호
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• pp.144-153
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• 2017

It was demonstrated that Gangjihwan (DF), which is the herbal composition composed of Ephedra intermedia, Lithospermum erythrorhizon, and Rheum palmatum, inhibits obesity and hepatic steatosis in high fat diet (HFD)-fed obese mice. The aim of this study was to determine the effects of DF on visceral obesity, hepatic inflammation and fibrosis and the mechanism of actions involved in this process using in vivo and in vitro approaches. DF was extracted with water (DF-FW), 30% grain alcohol (DF-GA30), and 70% grain alcohol (DF-GA70). Administration of DF to HFD-fed control mice decreased visceral tissue mass and visceral adipocyte size without adverse effects. Visceral fat mass was decreased by DF-GA30 and DF-GA70, and visceral adipocyte size by all three DF extracts compared with obese control mice. Histological analysis revealed that three kinds of DF extracts reduced toluidine blue-stained mast cells and collagen accumulation in the liver, the extents of which were most eminent in DF-GA70-treated mice. DF-GA70 decreased the mRNA levels of the inflammation ($TNF{\alpha}$ and VCAM-1), fibrosis (${\alpha}-SMA$), and apoptosis (caspase 3) genes, but increasing the anti-apoptosis gene (Bcl-2) mRNA levels in the liver of obese control mice. Consistent with the in vivo data, GA-70 also altered the expression of inflammation genes ($TNF{\alpha}$ and MCP-1) in HepG2 cells. These results indicate that DF not only inhibits visceral obesity, but also ameliorates visceral obesity-induced hepatic inflammation and fibrosis and that this process may be mediated by regulating the hepatic expression of inflammatory and fibrogenic genes.

• 대한핵의학회지
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• 제25권2호
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• pp.200-206
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• 1991

Arterial fraction of total hepatic blood flow was estimated by a new method, slope method, on radionuclid angiogram using $^{99m}Tc-DISIDA$ and was compared with that from $^{99m}Tc-Phytate$ radionuclide angiogram. This study included 11 of normal subjects, 37 of intermediate group with various liver diseases, and 25 patients with liver cirrhosis. We analyzed the datas with slope method from radionuclide angiograms and the results were compared with hepatic arterial fractions from uptake method, introduced by Lee et al. at 1986. The hepatic arterial fractions from radionuclide angiograms using $^{99m}Tc-DISIDA$ and $^{99m}Tc-Phytate$ were $0.32{\pm}0.09\;and\;0.31{\pm}0.11$ respectively in normal subjects, and $0.75{\pm}0.18\;and\;0.77{\pm}0.21$ respectively in patients with liver cirrhosis. The hepatic arterial fractions by the slope method was well correlated with those of the uptake method on $^{99m}Tc-DISIDA$ scan. There was high correlation between the hepatic arterial fractions from $^{99m}Tc-DISIDA$ and $^{99m}Tc-Phytate$ scans. Hepatic arterial fraction estimated by the slope method is a useful index for the diagnosis of liver cirrhosis and the evaluation of status of portal hypertension.

• 동의생리병리학회지
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• 제30권4호
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• pp.279-288
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• 2016

To observe the potential hepatoprotective effects of Gongjin-dan on the acute ethanol (EtOH)-induced liver damages in C57BL/6 mice with its possible action mechanisms. EtOH-mediated acute hepatic damages were induced by oral administration of EtOH total 3 doses. The changes on the body weight, liver weight, albumin, TG, AST, ALP, ALT, hepatic TG contents, hepatic antioxidant defense system, TNF-α, CYP 2E1 activity and mRNA expressions of hepatic lipogenic genes - SREBP-1c, SCD1, ACC1, FAS, PPARγ and DGAT2 or genes involved in fatty acid oxidation - PPARα, ACO and CPT1 were observed with final liver histopathological inspections after 15 days of continuous administration of silymarin 200 mg/kg, Gongjin-dan (GJD) 400, 200 and 100 mg/kg. The results were compared with silymarin 200 mg/kg treated mice. Marked decreases of body and liver weights, increases of serum AST, ALT, Albumin and TG levels, hepatic TG contents, TNF-α level, CYP 2E1 activity and mRNA expressions of hepatic lipogenic genes or decreases mRNA expressions of genes involved in fatty acid oxidation were observed with histopathological changes related hepatosteatosis increases of immunolabelled hepatocytes, as the results of a binge drinking of EtOH in the present study. Also destroys of hepatic antioxidant defense systems were demonstrated in EtOH control mice as compared with intact vehicle control mice, respectively. The results suggest that oral administration of 400, 200 and 100 mg/kg of GJD favorably protected the liver damages from acute mouse EtOH intoxications.

• 한국식품영양학회지
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• 제11권5호
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• pp.542-549
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• 1998

Dietary orotic acid is known to induce the fatty liver. Fatty acid profiles in the lipid fraction of the liver and the serum in rats fed with or with orotic acid diet were analyzed. In all the hepatic lipid fraction of rats fed on the supplemented orotic acid diet, there was a significant increased in linoleic acid. In addition, linoleic acid was also increased in the triacylglycerol fraction of hepatic endoplasmic reticulum and the triacylglycerol and diacylglycerol fractions of hepatic Golgi apparatus of the orotic acid-feeding rats. In the time course study of the fatty acid profile in the hepatic triacylglycerol and diacylgycerol fractions, an increase of linoleic acid was observed similarly in the initial stages of orotic acid intake in the both fractions. However, linoleic acid in the serum triacylglycerol fraction of orotic acid-feeding rats increased from day 1, but it began to decrease the increment from day 2, resulting in the lower level of linoleic acid in the serum triacylglycerol fraction of orotic acid-feeding rats than that of rat fed a orotic acid-free diet after 10 days. Oleic acid (18:1) was increased in the only cholesteryl ester fraction of helpatic. However, oleic acid level in other fractions was not changed. The compositions of 14:0, 16:0 and 18:0 was reduced in the hepatic triacylogylcerol, diacylglycerol and cholesteryl ester fractions by orotic acid-feeding. However, these saturated fatty acids were significantly increased in the serum triacylglycerol fractions. The orotic acid indcued changes in linoleic acid level in hepatic triacylglycerol may be explained by the impaired fatty acid metabolism and limited excretion of this fatty acid from liver to serum.

• Journal of Nutrition and Health
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• 제31권2호
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• pp.126-134
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• 1998

Our previous study demonstrated that dietary taurine or glycine supplementation significantly lowered plasma and hepatic cholesterol and triglyceride concentrations in rats fed a cholesterol-free diet. In the present study, the effect of long term dietary taurine or glycine supplementation, for the purpose of preventing and/or treating of hyperlipidemia and other known biological functions, on plasma and hepatic free amino acid concentrations and profiles were evaluated in rats. Three groups of male rats(110-130g) were fed a control diet(CD), taurine-supplemented diets(TSD ; CD+ 1.5% taurine) or glycine-supplemented diet(GSD ; CD+1.5% glycine) for 5 weeks. Plasma and hepatic free amino acid concentrations were determined by an automated amino acid analyzer based on ion-exchange chormatography. The feeding of TSD for 5 weeks yielded a 444% higher plasma taurine concentration , and the feeding GSD for the same period resulted in a 143% higher plasma glycine level in rats compared to those fed DB. Hepatic taurine concentration was significantly higher in rats fed TSD(145% increase) compared to the control rats. However, hepatic glycine concentration was not influenced by dietary glycine supplementation , which implies that the massive dose of glycine entering the body was more rapidly metabolized or excreted than taurein. Dietary taurine or glycine supplementation resulted in similar changes in plasma free amino acid concentrations, except in levels of taurine and glycine. Plasma levels of histidine, lysine, phenylalanine , alanine, proline, hydroxypoline, $\alpha$-aminogutyric acid, cystathionine and ethanolamine were significantly higher in rats fed TSD or GSD than those fed GD. Glycine supplementation did not change hepatic free amino acid concentrations as compared to CD. Concentrations of most hepatic free amino acids were not influenced by dietary taurine supplementation with the exception of significantly higher levels of asparate and tyrosine(56-63% increase) and lower levels of histidine and glutamate(33-34% decrease) compared to the control rats. These results suggest long-term dietary taurine or glycine supplementation resulted in increases in most plasma free amino acid levels, but did not cause a characteristic change in plasma aminogram pattern compared to rats fed CD.

• 대한한방내과학회지
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• 제25권2호
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• pp.277-287
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• 2004

Objective : Diabetes is a disease in which the body does not produce or properly use insulin. Etiological studies of diabetes and its complications showed that oxidative stress might playa major role. Therefore, many efforts have been made to regulate oxygen free radicals for treating diabetes and its complications. Because Jindangwon has been known to be effective in treatment of diabetes, the methanol extract of Jindangwon was tested for its effectiveness in reducing the oxidative stress induced by Streptozotocin. Methods : Jindangwon was washed, dried in the shade and crushed. The crushed Jindangwon was extracted 3 times, each time with 3 volumes of methyl alcohol at $60^{\circ}C$ for 24 hours. The extract was filtered and evaporated under reduced pressure using a rotary evaporator to yield 30.6 g. Jindangwon extract was oral-administered to the diabetic rats induced by streptozotocin 50 mg per 1 kg of body weight for 15 days. The efficacy of the Jindangwon extract was examined with regard to the enzymatic pathways involved in the oxygen free radical production and the glutathione balance. Results : he effects of the methanol extract of Jindangwon in streptozotocin-induced diabetics rats with regard to body weight, blood glucose level, hepatic lipid peroxide level, hepatic xanthine oxidase activity and type conversion rate, hepatic glutathione level, hepatic glutathione peroxidase activity, hepatic glutathione reductase activity, hepatic aldose reductase activity, and hepatic sorbitol dehydrogenase activity were favorable enough to suggest that it is a cure for diabetes and its complications. Conclusions :These results support Jindangwon as an effective reducing agent for oxidative stress in the tissues and organs by regulating the production of oxygen free radicals. Jindangwon, in particular, shows promising results for its use as a cure, or preventative medicine for diabetes and its complications by reducing oxidative stress in beta-cells of the pancreas.