• Archives of Pharmacal Research
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• v.21 no.5
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• pp.508-513
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• 1998

The hepatoprotective effect of DA-9601, a quality-controlled extract of artemisisa asiatica, on liver damage induced by acetaminophen (APAP) and carbon tetrachloride ($CCI_{4}$) was investigated by means of serum-biochemical, hepatic-biochemical, and histopathological examinations. Doses of Da-9601 (10, 30, or 100 mg/kg) were administered intragastrically to each rat on three consecutive days i.e. 48 h, 24 h and 2 h before a single administration of APAP (640 mg/kg, i.p.) or $CCI_{4}$ (2 ml/kg, p.o.). Four h and 24 h after hepatotoxin treatment, the animals were sacrificed for evaluation of liver damage. Pretreatment of Da-9601 reduced the elevation of serum ALT, AST. LDH and histopathological changes such as centrilobular necrosis, vacuolar degeneration and inflammatory cell infiltration dose-dependently. Da-9601 also prevented APAP- and $CCI_{4}$-induced hepatic glutathione (GSH) depletion and $CCI_{4}$-induced increase of hepatic malondialdehyde (MDA), a parameter of lipid peroxidation, in a chemically induced liver injury by complex mechanisms which involve prevention of lipid peroxidation and preservation of hepatic GSH.

• 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.

• Journal of Life Science
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• v.31 no.9
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• pp.796-805
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• 2021

Hepatic endoplasmic reticulum (ER) stress contributes to the development of steatosis and insulin resistance. The components of unfolded protein response (UPR) regulate lipid metabolism. Recent studies have reported an association between ER stress and aberrant cellular lipid control; moreover, research has confirmed the involvement of sterol regulatory element-binding proteins (SREBPs)-the central regulators of lipid metabolism-in the process. However, the exact role of SREBPs in controlling lipid metabolism during ER stress and its contribution to fatty liver disease remain unknown. Here, we show that SREBP-1c deficiency protects against ER stress-induced hepatic steatosis in mice by regulating UPR, inflammation, and fatty acid oxidation. SREBP-1c directly regulated inositol-requiring kinase 1α (IRE1α) expression and mediated ER stress-induced tumor necrosis factor-α activation, leading to a reduction in expression of peroxisome proliferator-activated receptor γ coactivator 1-α and subsequent impairment of fatty acid oxidation. However, the genetic ablation of SREBP-1c prevented these events, alleviating hepatic inflammation and steatosis. Although the mechanism by which SREBP-1c deficiency prevents ER stress-induced inflammatory signaling remains to be elucidated, alteration of the IRE1α signal in SREBP-1c-depleted Kupffer cells might be involved in the signaling. Overall, the results suggest that SREBP-1c plays a crucial role in the regulation of UPR and inflammation in ER stress-induced hepatic steatosis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.1
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• pp.81-86
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• 2002

The present study was conducted to investigate the effect of dietary supplementation of vitamin A or $\beta$-carotene on oxidative damage induced by acute ethanol administration. Sprague-Dawley rats were fed on the experimental diets supplemented with retinyl acetate (2.86 mg/kg diet) or $\beta$-carotene (15.2 mg/kg diet) for 5 weeks. After fed the diet, rats were administered 20% ethanol solution (3g/kg B.W.) acutely. Lipid peroxide values in hepatic tissue, hepatic antioxidative enzyme activities and contents of antioxidative nutrient such as vitamins A and E in serum and hepatic tissue were measured. Hepatic level of malondialdehyde decreased in $\beta$-carotene group compared to the control group. However, there was no significant difference between retinal acetate and $\beta$-carotene groups. Superoxide dismutase activity was higher in retinal acetate group than in the control group. Hepatic glutathione-S-transferase activity of retinal acetate and $\beta$-carotene groups significantly decreased as compared with that of control group. The hepatic content of retinol increased in retinal acetate and $\beta$-carotene groups, especially, in retinyl acetate group. But there was no significant difference in serum content of retinol among the groups. Hepatic content of $\alpha$-tocopherol was significantly increased in retinyl acetate and $\beta$-carotene groups. In conclusion, acute ethanol administration might induce lipid peroxidation, and the dietary supplementation of retinyl acetate or $\beta$-carotene improve partly the antioxidative system through activation of superoxide dismutase and retention of hepatic $\alpha$-tocopherol in ethanol-treated rats.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.8
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• pp.1310-1317
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• 2003

Effects of dietary cholesterol and/or taurine supplementation on plasma and hepatic lipid peroxidation status and antioxidant enzyme activities were evaluated in rats fed one of the following semisynthetic diets for 5 weeks: control diet (CD, cholesterol-free and taurine-free diet); high cholesterol diet (HCD, CD+1.5% cholesterol): high taurine diet (HTD, CD+1.5% taurine): high cholesterol and high taurine diet (HCHTD, HCD + 1.5% taurine). Plasma malondialdehyde (MDA) level was not influenced by dietary cholesterol or taurine supplementation, while hepatic MDA level was 70% higher in rats fed HCD compared to the value for CD rats (p<0.05). Our observation that taurine supplementation significantly decreased the hepatic MDA level of rats fed HCD, but failed to decrease lipid peroxidation of rats fed CD indicates that the protective effect of taurine in the liver against lipid peroxidation is manifested only under the hypercholesterolemic environment. Plasma and hepatic glutathione peroxidase (GSH-Px) activities were not affected by dietary supplementation of cholesterol or taurine. However, hepatic superoxide dismutase (SOD) activity was significantly reduced by dietary taurine supplementation (p <0.05), and thus significantly lower in rats fed HTD compared to the value for CD (p<0.05). Plasma total cholesterol concentration was positively correlated with hepatic cholesterol concentration as expected (r=0.712, p<0.001). Plasma (r=0.399, p<0.05) and hepatic cholesterol levels (r=0.429, p<0.05) showed a significantly positive correlation with hepatic MDA concentration, respectively. Plasma taurine concentration was negatively correlated with hepatic SOD activity (r=-0.481, p<0.01), and tended to be negatively correlated with hepatic GSH-Px activity without showing statistical significance (r=-0.188, p<0.05). These results indicate an antioxidative effect of taurine in rats with elevated level of lipid Peroxidation due to high intake of dietary cholesterol. Future application of taurine as a safe candidate for a hypolipidemic agent without adversely affecting body's antioxidant defense system is speculated.

• Korean Journal of Veterinary Research
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• v.32 no.3
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• pp.347-356
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• 1992

In oriental medicine, Artemisia Iwayomogi(Compositae) has been used clinically for jaundice, hepatitis, liver cirrhosis etc. The purposes of present study were to examine pharmacological effects of Artemisia lwayomogi water extract(AIWE) on weights of body, liver, kidney, spleen and adrenal, and on biochemical parameters (activities of AST, ALT and LDH, contents of cholesterol and triacylglycerol, and levels of hepatic lipid peroxide) against hepatic injury by carbon tetrachloride($CCl_4$) in rats. The results were as follow; 1. Body weights were reduced by $CCl_4$. In AIWE pretreatment groups, reduction of body weights was inhibited at 48 hours. Increased liver weights by $CCl_4$ were reduced in proportion to numbers of treatment of AIWE in AIWE pre- and posttreatment groups. Increased kidney weights by $CCl_4$ were reduced in AIWE pretreatment groups at 72 hours. Increased weights of spleen and adrenal by $CCl_4$ were not affected by AIWE treament. 2. Increased AST activities by $CCl_4$ were significantly (p<0.05) decreased in AIWE posttreatment groups at 48 and 72 hours. Increased ALT activities by $CCl_4$ were significantly(p<0.05) decreased in AIWE posttreatment groups at 48 hours. Increased LDH activities by $CCl_4$ were very significantly (p<0.01, p<0.001) decreased in AIWE posttreatment groups at 48 and 72 hours, respectively. 3. Increased cholesterol contents by $CCl_4$ were significantly (p<0.05) decreased in AIWE posttreatment groups at 24 and 48 hours. Decreased triacylglycerol contents by $CCl_4$ were significantly (p<0.05) increased in AIWE posttreatment at 48 and 72 hours. 4. Increased hepatic lipid peroxide levels by $CCl_4$ were significantly (p<0.05, p<0.01) decreased in AIWE posttreatment groups at 48 and 72 hours, respectively. In conclusion, AIWE did not affect normal liver function and had property of antioxidant, due to reduced lipid peroxidation by $CCl_4$. AIWE seems to have hepatoprotective effects rather than direct preventive effects to $CCl_4$-induced necrotic degeneration of liver cell, cholestasis and damages in metabolism of lipid.

• Journal of Nutrition and Health
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• v.6 no.4
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• pp.37-53
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• 1973

For the elucidation of the metabolic effects due to alcoholic drink and moldy rice intake author designed two experiments as follows. In the first experiment, sixty male and female rats, divided into six groups, 10 rats each in both sexes, were given 7.5% sucrose-30% alcohol solution (Jinro-Soju) and diets varied of fat content (2%, 7%, 30% of diet) and protein quality (casein, bean, anchovy) for 6 weeks. In the Second experiment, six groups of rats, 10 male rats each, were fed the diets containing zero, 5%, 10%, 25%, 50%, and 100% moldy rice contaminated Penicillium Islandicum and the experimental periods were 4 weeks and 6 weeks. The results of these studies due to the toxicity of alcohol consumption and moldy rice ingestion of the fatty liver production and the other effects are as follows. 1. Food intake of alcohol consumed groups decreased to 50%-70% of that of standard group. In the second study, there was no significant differences on food intake due to the different contents of moldy rice and experimental period. 2. On the view paint of body weight gain, the body weight of alcohol consumed groups gained much less than that of standard group, because food consumption was decreased due to alcohol ingestion. 3. In comparison of F.E.R. and P.E.R. between standard and experimental groups, there was no significant differences in this study. 4. As a matter of fact, there was no significance on the nitrogen balance in both studies. 5. From the result of hematology, R.B.C. counts, W.B.C. counts, hemoglobin, and hematocrit showed normal values in all groups including in this study. So we might conclude that the toxicity of alcohol and moldy rice do not effect significantly on blood picture. 6. The larger organs shrank on the range of 20%-70% of that against standard group in this study. The major reason for the shrinkage of organs might be account of decreased food consumption due to alcoholic drink. There was no great changes on the organ weight due to the ingestion of moldy rice. 7. The nitrogen content in various organs in both experiments was revealed at the normal level for the worst condition in terms of the least food intake. In other word, it was noteworthy that the concentration of nitrogen in various organs was kept at the normal ratio as standard groups under the circumstances of this study. 8. The lipid content in the liver of rats fed alcohol and diets containing either various lipid contents or protein quality did not increase. Hepatic lipids accumulation due to the dietary fat content was observed, but there wvas no significances among the compared groups. In the second experiment, the difference of hepatic lipid content between the moldy rice groups and standard group was not showed. In addition to the result of total lipid, hepatic free cholesterol, free fatty acid, and triglyceride did not change in both studies, we might conclude that the toxicity of alcohol and moldy rice could not effect on the hepatic lipid contents. 9. There was no significant differences on the serum glucose level between alcohol groups and standard group. In the second experiment, serum glucose level increase in 6th week compared with in 4th week, but there was no significant differences.

• Nutritional Sciences
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• v.6 no.3
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• pp.141-147
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• 2003

Fruits and vegetables reportedly have a protective effect against hyperlipidemia and oxidative disease. Accordingly, this study aimed to investigate the lipid-lowering effect and antioxidative capacity of persimmon leaf extract (PLE) in rats fed a high-cholesterol diet. Male rats were fed a high-cholesterol (1% wt/wt) or high-cholesterol diet supplemented with Lovastatin (0.02% wt/wt) or PLE (0.2% wt/wt) for 5 weeks. The concentration of plasma total cholesterol was significantly lower in the PLE group than in the lovastatin group. However, the concentration of plasma HDL-cholesterol and the ratio of HDL-cholesterol/total-cholesterol (%) were significantly higher in the PLE group than in the control group. The PLE supplement also significantly lowered the contents of hepatic cholesterol and triglyceride. In comparing fecal sterol contents, the PLE group saw a significant increase of both neutral and acidic sterol compared to the other groups. The PLE supplement significantly lowered plasma GOT and GPT activity, which ave indices of hepatic toxicity. Plasma TBARS concentration was significantly lower in the PLE group than in the control group, while hepatic TBARS level was not significantly different between the groups. In a comparison of hepatic antioxidant parameters, SOD, catalase and GSH-Px activity were significantly higher in the PLE group than in the control group. However, the PLE supplement significantly towered antioxidant enzyme activity in the erythrocyte. Furthermore, these results suggest that supplementation of PLE promoted the excretion of fecal sterols, thereby leading to decreased absorption of dietary cholesterol. In addition, PLE may play an important role in regulating antioxidative capacities by altering SOD and ChT activity.

• Toxicological Research
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• v.34 no.1
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• pp.23-29
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• 2018

Ethanol-induced fat accumulation, the earliest and most common response of the liver to ethanol exposure, may be involved in the pathogenesis of liver diseases. Isoliquiritigenin (ISL), an important constituent of Glycyrrhizae Radix, is a chalcone derivative that exhibits antioxidant, anti-inflammatory, and phytoestrogenic activities. However, the effect of ISL treatment on lipid accumulation in hepatocytes and alcoholic hepatitis remains unclear. Therefore, we evaluated the effect and underlying mechanism of ISL on ethanol-induced hepatic steatosis by treating AML-12 cells with 200 mM ethanol and/or ISL ($0{\sim}50{\mu}M$) for 72 hr. Lipid accumulation was assayed by oil red O staining, and the expression of sirtuin1 (SIRT1), sterol regulatory element-binding protein-1c (SREBP-1c), AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor alpha ($PPAR{\alpha}$) was studied by western blotting. Our results indicated that ISL treatment upregulated SIRT1 expression and downregulated SREBP-1c expression in ethanol-treated cells. Similarly, oil red O staining revealed a decrease in ethanol-induced fat accumulation upon co-treatment of ethanol-treated cells with 10, 20, and $50{\mu}M$ of ISL. These findings suggest that ISL can reduce ethanol induced-hepatic lipogenesis by activating the SIRT1-AMPK pathway and thus improve lipid metabolism in alcoholic fatty livers.

• Journal of Nutrition and Health
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• v.35 no.6
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• pp.643-649
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• 2002

This study was done to investigate effects of ${\gamma}$-irradiated pork feeding on the formation of glutathione S-transferase placental form positive (GST-P$^{+}$) foci, lipid peroxidation, cytochrome P450 system and microsomal glucose 6-phosphatase activity in diethylnitrosamine (DEN)-initiated rat hepatocarcinogenesis. Weaning Sprague-Dawley male rats were fed the diet containing ${\gamma}$-irradiated ground pork at the dose of 0, 3, 10, 30 kGy as a 20％ of protein source for 8 weeks. One week after feeding, rats were intraperitoneally injected twice with a dose of DEN (50 mg/kg BW). As a promote.,0.05％phenobarbital was fed in drinking water from one week after DEN treatment until the end of experiment. At the end of 8th week, rats were sacrificed and hepatic GST-P$^{+}$ foci, microsomal malondialdehyde (MDA) and conjugated diene contents were determined. In addition, cytochrome P450 content and the activities of NADPH cytochrome P450 reductase and glucose 6-phosphatase were also measured. There was no significant effect by gamma irradiation on microsomal MDA content, conjugated diene, cytochrome P450 content and activities of NADPH cytochrome P450 reductase and glucose 6-phosphatase. However with DEN treatment, microsomal MDA content showed a increasing tendency. Cytochrome P450 content was also significantly increased while microsomal glucose 6-phophatase activity was significantly decreased with DEN treatment. However the activity of NADPH cytochrome P450 reductase was not affected. An interesting finding in this study was that the number and area of hepatic GST-P$^{+}$ foci of rats fed gamma irradiated pork were tended to be decreased by high dose of irradiation, but were not significantly different. These results might imply that the consumption of low dose of gamma irradiated pork does not affect the formation of hepatic GST-P$^{+}$ foci and lipid peroxide and membrane stability.ability.