• 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.

• Nutritional Sciences
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• v.9 no.2
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• pp.82-91
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• 2006

This study was performed to investigate the effect of normal diet with or without naringin supplement on the lipid and antioxidant metabolism in ethanol-treated rats for a short tenn. Male Sprague-Dawley rats were divided into three groups (n=10), which were assigned to one of three dietary categories : $E_8$ : ethanol diet for 8 wks, $E_4N_4$ : ethanol diet for the first 4 wks and normal diet for the last 4 wks, $E_4Nna_4$ : ethanol diet for the first 4 wks and normal diet with naringin supplement for the last 4 wks. Plasma total cholesterol concentrations were significantly higher in ethanol fed rats for 8 weeks. The HDL-C/total-C ratios of the $E_4N_4$ and the $E_4Nna_4$ groups were significantly higher than that of the $E_8$ group, while the atherogenic index was lower in the $E_4N_4$ and the $E_4Nna_4$ groups than in the $E_8$ group. The $E_4N_4$ and $E_4Nna_4$ diets significantly lowered both the hepatic cholesterol and triglyceride levels compared to the $E_8$ group. Accumulation of hepatic lipid droplets was observed to be the highest in the $E_8$ group. In the current study, the naringin supplement to normal diet significantly lowered both the hepatic HMG-CoA reductase and ACAT activities in ethanol pre-treated rats for 4 weeks. Antioxidant enzyme activities were also upregulated when ethanol feeding was ceased. Naringin supplement given for 4 weeks after ethanol cessation resulted in a significant decrease in the plasma cholesterol and hepatic lipids and plasma TBARS as well as the hepatic HMG-CoA reductase and ACAT activities compared to the rats given ethanol diet for the entire 8 weeks. Replacement of normal diet following a short tenn ethanol feeding was effective for the recovery of ethanol-induced fatty liver and for normalizing plasma and hepatic lipid profiles and antioxidant enzyme activities, regardless of an additional phytochemical supplement, naringin. The effect of naringin could seemingly be more evident if its supplementation period had been extended longer than 4 weeks after ethanol cessation.

• BMB Reports
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• v.32 no.4
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• pp.331-338
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• 1999

Ethanol catabolism is thought to produce metabolic disorders resulting in alcoholic liver disease. To investigate the mutual effects of ethanol catabolism and cholestasis induced by common bile duct ligation on the activities of carboxylesterase, we have determined the enzyme activities in rat hepatic (cytosolic, mitochondrial, and microsomal) preparations as well as in rat serum using ten animal models: normal rats (group 1), sham-operated rats (group 2), common bile duct-ligated rats (group 3), ethanol-intoxicated rats (group 4), sham-operation plus chronic ethanol-intoxicated rats (group 5), common bile duct-ligated plus chronic ethanol-intoxicated rats at 1.5h and 24h (groups 7A and 7B), and duct-ligated and acute ethanol intoxicated rats at 1.5 h and 24 h (groups 8A and 8B). The $K_m$ and $V_{max}$ values of carboxylesterase from these hepatic preparations of cholestatic rat liver combined with chronic ethanol intoxication were also measured by using ethyl valerate as the substrate from the 14th day post-ligation. Carboxylesterase activities of all hepatic preparations and rat serum (group 3) showed significant decreases compared to the activities from the sham-operated control (group 2). Enzyme kinetic parameters indicated that $V_{max}$ of carboxylesterase from all the hepatic preparations in cholestatic rats (group 3) decreased significantly, although the $K_m$ values were about the same as in the sham-operated control (group 2). When cholestasis was combined with chronic ethanol intoxication (group 6), carboxylesterase activities showed further decrease in all the hepatic preparations and serum compared to the control activity (group 5). The $V_{max}$ also decreased significantly, although $K_m$ values did not change. When common bile duct ligation was combined with acute ethanol intoxication (group 8), the enzyme activities in the rat liver and serum showed significant decrease compared to the activity from acute ethanol-intoxicated rats (group 7). However, quite contrary to this, the activities of serum from acute ethanol intoxication 1.5 h (group 7A) increased significantly compared to the activities in the normal control (group 1). These results, therefore, suggest that the biosynthesis of hepatic carboxyl-esterase seems to decrease when cholestasis is combined with chronic and acute ethanol intoxication, and the decrease in activity is more significant than from cholestasis alone.

• Toxicological Research
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• v.4 no.1
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• pp.13-22
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• 1988

The inhibitory effect of three polyacetylene compounds, panaxydol, panaxynol and panaxytriol isolated from Panax ginseng C.A. Meyer on $CCl_4$induced lipid peroxidation in vivo and in vitro hepatic microsomal lipid peroxidation induced by ADP-$Fe^{3+}$, NADPH and NADPH-cytochrome P-450 reductase were investigated. Their effects on lowering the lipid peroxide levels both in serum and liver and lowering the serum enzyme (GOT, GPT, LDH) activities without the $CCl_4$-induction were also determined. Male ICR mice were pretreated i.p. with polyacetylene compounds or DL-${\alpha}$-tocopherol before administration of $CCl_4$ i.p. and 20 hr after the administration of $CCl_4,$ serum and liver were analyzed. Hepatic microsome was isolated and used for the in vitro NADPH-dependent lipid peroxidation system. Except for panaxynol, treatment with polyacetylenes to control mice did not reduce the levels of lipid peroxides and serum enzyme activities. Panaxynol itself inhibited lipid peroxidation in the liver of normal mice. Polyacetylene compounds protected from the $CCl_4$-induced hepatic lipid peroxidation and lowered serum lipid peroxide levels. Polyacetylenes also inhibited the in virto hepatic microsomal lipid peroxidation in a dose-dependent manner. The results suggest that panaxydol, panaxynol and panaxytriol seem to be the antioxidant components which contribute the anti-aging activities of Panax ginseng C.A. Meyer.

• Preventive Nutrition and Food Science
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• v.16 no.2
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• pp.95-103
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• 2011

This study was performed to investigate the antioxidant mechanism of tomato wine with varying lycopene content in rats fed a high fat diet (HFD). Male Sprague-Dawley rats were randomly divided into five groups (n=10 per group) and fed an HFD (35% of total energy from fat) plus ethanol (7.2% of total energy from alcohol), tomato wine with varying lycopene content (0.425 mg%, 1.140 mg% or 2.045 mg% lycopene) or an isocaloric control diet for 6 weeks. Mice fed HFD plus ethanol significantly increased erythrocyte hydrogen peroxide and thiobarbituric acid reactive substances (TBARS) levels with increases in activities of erythrocyte antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) compared to pair-fed rats. Supplementation of tomato wine with varying lycopene content decreased ethanol-mediated increases of erythrocyte lipid peroxidation and antioxidant enzyme activities in HFD-fed rats, and tomato wine with higher lycopene appeared to be more effective. Tomato wine also dose-dependently lowered TBARS levels with decreased pro-oxidant enzyme, xanthine oxidase (XOD) activity in plasma of HFD-fed rats. In contrast to erythrocytes, the inhibitory effects of tomato wine on hepatic lipid peroxidation were linked to increased hepatic antioxidant enzymes (SOD and CAT) and alcohol metabolizing enzyme (alcohol dehydrogenase and aldehyde dehydrogenase) activities. There were no significant differences in hepatic XOD and cytochrome P450-2E1 activities among the groups. Together, our data suggest that tomato wine fortified with lycopene has the potential to protect against ethanol-induced oxidative stress via regulation of antioxidant or pro-oxidant enzymes and alcohol metabolizing enzyme activities in plasma, erythrocyte and liver.

• BMB Reports
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• v.32 no.1
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• pp.67-71
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• 1999

We have investigated the effect of cholestasis on the closely related acyl-CoA:amino acid N-acyltransferase, benzoyltransferase, and phenylacetyltransferase activities in rat liver. Benzoyltransferase and phenylacetyltransferase activities in the liver cytosol, mitochondria, and microsome were investigated for a period of 42 d after common bile duct ligation. Both the mitochondrial and microsomal benzoyltransferases showed significant increase in their activities between the 1st and 7th day after common bile duct ligation, although the cytosolic benzoyltransferase activity did not show a significant change compared to the activities from the sham-operated control. The cytosolic phenylacetyltransferase activity showed a significant increase between the 1st and 2nd day, the mitochondrial activity showed a significant increase between the 2nd and 7th day, and microsomal activity showed a significant increase between the 1st and 7th day, respectively. Enzyme kinetic parameters of hepatic benzoyltransferase were analyzed using benzoyl coenzyme A as a substrate with the preparations from the 1st day post-ligation. Enzyme parameters of hepatic phenylacetyltransferase were also analyzed using phenylacetyl coenzyme A as a substrate with the preparations from the 2nd day post-ligation. The results indicated that although the $K_m$ values of these enzymes were about the same as the sham-operated control, the $V_{max}$ values of both enzymes increased significantly. These results, therefore, suggest that the biosynthesis of benzoyltransferase and phenylacetyltransferase has been induced in response to cholestasis.

• Biomolecules & Therapeutics
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• v.17 no.2
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• pp.188-198
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• 2009

This work was conducted to investigate the effect of bisphenol A (BPA) on estradiol (E2) 2-and 4-hydroxylase activities in the liver, kidney and lung tissues of male and female rats. After intraperitoneal administration of BPA to male and female rats for 4 days at 0, 10, and 50 mg/kg, the conversion of the substrate for hepatic and extra-hepatic enzyme activities was measured by GC/MSD. The result showed decreases of body and organ weights at 50 mg/kg BPA of male and female rats. Male hepatic E2 2-hydroxylase activity was inhibited by 68% at 10 mg/kg and by 82% at 50 mg/kg BPA. Female hepatic E2 2-hydroxylase activity was decreased by 46% at 10 mg/kg and by 56% at 50 mg/kg to the control. E2 4-hydroxylase was inhibited by 57 and 57% at 10 mg/kg and 54 and 78% at 50 mg/kg in liver of female and male, respectively. The urinary excretion rate of 2-hydroxyestradiol (2-OHE), androsterone and testosterone in urine of female rats with 50 mg/kg BPA were decreased significantly. The results showed that 50 mg/kg BPA was decreased E2 2-and 4-hydroxylase activities in liver, but not in other tissues. The urinary excretion rates of 2-OHE, androsterone and testosterone were also decreased. In liver, estrogenic enzyme activity were higher in male than female. These results suggest that BPA can disrupt estrogen metabolism by suppressing E2 2-and 4-hydroxylase activities in the liver of male and female rats.

• Korean Journal of Pharmacognosy
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• v.17 no.3
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• pp.189-194
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• 1986

The single acute treatment of mice with the steam distillate, non-volatile ether extract and methanol extract from mace, arils of Myristica fragrans(Myristicaceae) caused a significant prolongation of hexobarbital-induced narcosis, an increase in strychnine toxicity as well as a significant decrease in hepatic microsomal drug metabolizing enzyme activities. On seven daily consecutive administrations, however, the duration of narcosis was markedly shortened and significant increases in the hepatic enzyme activities were shown. From the non-volatile ether fraction, macelignan, a new lignan, mp $70{\sim}72^{\circ}$ was isolated as an active principle.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.1
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• pp.92-97
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• 2002

The effects of Pueraria flos (PF) and Pueraria radix (PR) water extract on the hepatic alcohol metabolic enzyme activities were examined in rats that were orally administered ethanol (25% v/v, 5g/kg body weight/day) for 5 weeks. The PF and PR water extract were supplemented in a diet, based on 1.2 g or 2.4 g of raw PF or PR/kg body weight/body. Alcohol administration without the PF or PR supplementation significantly decreased net weight gain, feed intake and feed efficiency ratio. However. both dose of the PF of PR supplementation resulted in significant enhancement of growth and suppression of increased relative weight of liver, brain and heart by alcohol administration. Activities of hepatic alcohol dehydrogenase and microsomal ethanol oxidizing system were higher in the alcohol treated group than in the normal group, while aldehyde dehydrogenase activity was significantly lowered in the alcohol treated group. The hepatic metabolic enzyme activities altered by alcohol administration were normalized by both doses of PF or PR supplement. Hepatic monoamine oxidase activity and hydrogen peroxide, which were significantly higher in the alcohol treated group than in the normal group, were also decreased by the supplementation with either PF or PR. These results indicate that low-or high-supplementation of either water extract PF or PR may alleviate ethanol-induced hepatotoxicity by altering alcohol metabolic enzyme activities.

• Korean Journal of Pharmacognosy
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• v.15 no.2
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• pp.91-97
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• 1984

The investigation was aimed to study the effect of ginseng ethanol extract on the hepatic ethanol-metabolizing enzyme activity in vivo. The extract (100mg/kg/day) was administered orally to Sprague-Dawley rats for $7{\sim}10$ days and their microsomal ethanol oxidizing system(MEOS) and catalase activities were measured. The MEOS activity in the rat treated with the extract was not significantly different from that of the normal group. Microsomal fraction containing MEOS was separated and the MEOS activity was measured after preincubation for 5, 60 and 180 min, respectively. There were no significant differences in MEOS activities between the normal and treated groups preincubated for 5, 60 and 180 min. The activity in the rat treated with single i.p. injection of 95% $CCl_4$ (0.5ml/kg) was decreased by 48%, compared to the normal group and in the rat treated with the extract (100mg/kg) for $7{\sim}10$ days, the decrease of the MEOS activity was potentiated. Catalase activity in the rat treated with the extract (100mg/kg) was similar to that obtained from the normal group.