• Nutrition Research and Practice
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• v.6 no.2
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• pp.113-119
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• 2012

Guinea pigs were fed a hypercholesterolemic diet (0.25 g/100 g cholesterol) and randomly allocated either to a Control group (n = 9) or to a Lutein (0.1 g/100 g) group (n = 10) for 12 weeks to evaluate oxidative stress and inflammation in both liver and eyes. Malondialdehyde (MDA) concentrations and inflammatory cytokines were measured as well as hepatic nuclear factor-kappaB (NF-${\kappa}B$) binding. Lutein concentrations were greater in eyes ($P$ < 0.01) and liver ($P$ < 0.001) in the Lutein group. All guinea pigs had high concentrations of hepatic cholesterol as well as high plasma ALT and AST levels indicative of liver injury. However, the Lutein group had 43% lower hepatic free cholesterol than the Controls ($P$ < 0.05). Hepatic MDA and MDA in the eye were lower in the Lutein compared to the Control group ($P$ < 0.05). Hepatic tumor necrosis factor-${\alpha}$ was 32% lower in the Lutein group ($P$ < 0.05). Lastly, the Lutein group presented lower NF-${\kappa}B$ DNA binding activity than the Control group ($P$ < 0.001). These results suggest that in the presence of high cholesterol, lutein exerts both antioxidant and anti-inflammatory effects, which can be explained by attenuated NF-${\kappa}B$ DNA binding activity. Furthermore, results also suggest that lutein accumulates in the eyes of guinea pigs to protect against oxidative stress.

• Journal of Microbiology and Biotechnology
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• v.23 no.11
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• pp.1569-1576
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• 2013

In mice, supplementation of t10,c12 conjugated linoleic acid (CLA) increases liver mass and hepatic steatosis via increasing uptake of fatty acids released from adipose tissues. However, the effects of t10,c12 CLA on hepatic lipid synthesis and the associated mechanisms are largely unknown. Thus, we tested the hypothesis that gut microbiota-producing t10,c12 CLA would induce de novo lipogenesis and triglyceride (TG) synthesis in HepG2 cells, promoting lipid accumulation. It was found that treatment with t10,c12 CLA ($100{\mu}M$) for 72 h increased neutral lipid accumulation via enhanced incorporation of acetate, palmitate, oleate, and 2-deoxyglucose into TG. Furthermore, treatment with t10,c12 CLA led to increased mRNA expression and protein levels of lipogenic genes including SREBP1, ACC1, FASN, ELOVL6, GPAT1, and DGAT1, presenting potential mechanisms by which CLA may increase lipid deposition. Most strikingly, t10,c12 CLA treatment for 3 h increased phosphorylation of mTOR, S6K, and S6. Taken together, gut microbiota-producing t10,c12 CLA activates hepatic de novo lipogenesis and TG synthesis through activation of the mTOR/SREBP1 pathway, with consequent lipid accumulation in HepG2 cells.

• Environmental Analysis Health and Toxicology
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• v.24 no.4
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• pp.303-309
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• 2009

Hepatic antioxidant defense systems were examined in rats treated with tetrabromobisphenol-A (TBBPA), a brominated flame retardant, at the doses of 0, 250, 500 and 1,000 mg/kg for four weeks. Hepatic ratio of glutathione disulfide to glutathione (GSH) and levels of malondialdehyde, oxidative stress markers were not changed in rats treated with TBBPA. Hepatic expression of antioxidant enzymes including GSH peroxdiase-1 (GPX-1)/GSH reductase (GR), alpha-, mu- and pi-class glutathione-S-transferase (GST) and gamma-glutamylcysteine ligase catalytic subunit was determined using immunoblot analysis. Alpha-class GSTs, GPX-1 and GR levels were significantly decreased in rats treated with TBBPA at the dose of 500 or 1,000 mg/kg. These results show that TBBPA results in down-regulation of hepatic expression of antioxidant enzymes related with GSH, suggesting the liver in TBBPA-treated rats may be more sensitive to oxidants.

• 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.

• Nutritional Sciences
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• v.7 no.3
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• pp.138-143
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• 2004

Conjugated linoleic acid (CLA) has been shown to have a range of biological activities, including anti-carcinogenic, anti-atherosclerotic, anti-adipogenic and anti-diabetogenic effects. Recent reports also showed that CLA has free radical scavenging capacity, which may have health benefits for human beings. The current study was performed to investigate the effect of structured lipid (SL)-containing CLA on plasma lipids and hepatic antioxidant enzyme activity. Sprague-Dawley mts were fed 5% and 10% SL-containing normal diet for 6 wks and these groups were compared to rats fed 5% and 10% corn oil. In plasma lipids, total-cholesterol was not affected by fat source or dietary fat level while triglyceride level decreased significantly in groups fed 10% fat diet compared to the other groups. Plasma thiobarbituric acid reactive substances (TBARS) level decreased significantly in the S5 and S10 groups compared to the C5 and C10 groups, although hepatic TBARS level was not altered by fat source. On the other hand, in terms of hepatic antioxidant enzyme activity, superoxide dismutase activity increased in the S10 group, whereas catalase activity decreased in the S10 group. Glutathione peroxidase activity decreased significantly in the SL groups compared to the C5 group. Glutathione reductase activity increased and glucose-6-phosphate dehydrogenase activity decreased in the C10 group compared to the C5 and C5 groups. In conclusion, the free radical scavenging activity of CLA seemed to suppress oxidative stress, which reduced lipid peroxidation resulting in lower hepatic antioxidant enzyme activity.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.1
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• pp.23-33
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• 2018

Cushing's syndrome (CS) is a collection of symptoms caused by prolonged exposure to excess cortisol. Chronically elevated glucocorticoid (GC) levels contribute to hepatic steatosis. We hypothesized that histone deacetylase inhibitors (HDACi) could attenuate hepatic steatosis through glucocorticoid receptor (GR) acetylation in experimental CS. To induce CS, we administered adrenocorticotropic hormone (ACTH; 40 ng/kg/day) to Sprague-Dawley rats by subcutaneous infusion with osmotic mini-pumps. We administered the HDACi, sodium valproate (VPA; 0.71% w/v), in the drinking water. Treatment with the HDACi decreased steatosis and the expression of lipogenic genes in the livers of CS rats. The enrichment of GR at the promoters of the lipogenic genes, such as acetyl-CoA carboxylase (Acc), fatty acid synthase (Fasn), and sterol regulatory element binding protein 1c (Srebp1c), was markedly decreased by VPA. Pan-HDACi and an HDAC class I-specific inhibitor, but not an HDAC class II a-specific inhibitor, attenuated dexamethasone (DEX)-induced lipogenesis in HepG2 cells. The transcriptional activity of Fasn was decreased by pretreatment with VPA. In addition, pretreatment with VPA decreased DEX-induced binding of GR to the glucocorticoid response element (GRE). Treatment with VPA increased the acetylation of GR in ACTH-infused rats and DEX-induced HepG2 cells. Taken together, these results indicate that HDAC inhibition attenuates hepatic steatosis through GR acetylation in experimental CS.

• Journal of Nutrition and Health
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• v.36 no.10
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• pp.990-996
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• 2003

This study was conducted to investigate the effects of Forsythia viridissima Lindl. (FVL) on antioxidative defense system and lipid peroxidation of liver in rats fed high-cholesterol diet. Sprague-Dawley male rats weighing 100 $\pm$ 10 g were randomly assigned into five experimental groups fed 0.5％ cholesterol ; HC group which was not supplemented FVL extract, 0.05％ methanol extract diet group (MSI group), 0.1％ methanol extract diet group (MS2 group), 0.025％ ethylacetate-souble fraction diet group (ES1 group) and 0.05％ ethylacetate-souble fraction diet group (ES2 group). Experimental diets were fed ad libitum to the rats for 3 weeks. The hepatic xanthine oxidase (XOD) activity in the MS2 group was decreased to 20％ as compared to HC group. The activities of hepatic superoxide dismutase (SOD) and catalase (CAT) were not significantly different among all the high cholesterol diet groups. The hepatic glutathione peroxidase (GSHpx) activity in MS2, ES2 groups were significantly increased as compared to HC group. The hepatic glutathione S-transferase (GST) activity in the MS2 group was increased to 20％ as compared to HC group. The levels of hepatic TBARS in the MS1, MS2, ES1 and ES2 groups were reduced by 13％, 21％, 13％ and 21％, respectively, as compared with HC group. The contents of lipofuscin in liver tissue was not significantly different among all the experimental groups. The results indicate that FVL extract may reduce oxidative damage by activating antioxidative defense system of liver in rats fed high-cholesterol diets.

• The Journal of Internal Korean Medicine
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• v.33 no.3
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• pp.306-316
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• 2012

Objectives : Mori Folium is used for hyperlipidemia or diabetes. The study was designed to test the anti-obesity effect of Mori Folium on body weight, hepatic fat accumulation and serum lipid level. Methods : The extract from Mori Folium was made by the pharmacy department of Kyung-hee oriental medical hospital. Normal diet, high-fat diet, 30% reduced diet and Mori Folium groups were set. The normal group was administered normal rat food, but the other three groups were administered high fat food. We measured body weight once a week. After 3 weeks experiment, hepatic lipid accumulations were measured. Also we compared serum lipid levels among the 4 groups after 3 weeks. Results : Mori Folium had no effect on body weight, but the 30% reduced diet had an inhibitory effect on body weight gain. Mori Folium had more inhibitory effect on hepatic fat accumulation than a 30% reduced diet. Mori Folium also has more inhibitory effect on serum triglyceride than 30% reduced diet. Conclusions : Mori Folium has anti-obesity effect on hepatic lipid accumulaion and serum triglyceride level in high fat diet induced rats.

• Molecular & Cellular Toxicology
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• v.2 no.2
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• pp.126-133
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• 2006

Thioacetamide (TA) is well known hepatotoxic and hepatocarcinogenic agent. TA also diminishes the contents of hepatic cytochrome P450 and inhibits the enzyme activity of the hepatic mixed function oxidases. TA metabolite, thioacetamide-s-oxide, is further transformed into a still unknown highly reactive metabolite that binds to macromolecules. In this study, we focused on TA-induced gene expression at hepatotoxic dose. Mice were exposed to two levels (5 mg/kg or 50 mg/kg i.p.) of TA, sampled at 6 or 24 h, and hepatic gene expression levels were determined to evaluate dose and time dependent changes. We evaluated hepatotoxicity by serum AST and ALT level and histopathological observation. Mean serum activities of the liver leakage enzymes, AST and ALT, were slightly increased compare to control. H & E and PAS evaluation of stained liver sections revealed TA-associated histopathological finding in mice. Centrilobular eosinophilic degeneration was observed at high dose-treated mice group. Hepatic gene expression was analyzed by QT clustering. Clustering of high dose-treated samples with TA-suggests that gene expressional changes could be associated from toxicity as measured by traditional biomarkers in this acute study.

• Molecular & Cellular Toxicology
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• v.5 no.4
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• pp.317-322
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• 2009

Hepatic fibrosis is one of chronic liver diseases which spread in worldwide and it has high risk to turn advanced cirrhosis and hepatocellualr carcinoma. Brassica family has been produced for commercial purpose and in Korea Brassica rapa (Turnip) is cultivated in Ganghwa County, Gyeonggi-do Korea and used for making Kimchi. Recently pharmacological effects of turnip have been known; diabete mellitus modulation, alcohol oxidization, and fibrosis inhibition. In previous study we found antifibrogenic effect of turnip water extract and in this study we made turnip nanoparticle to promote turnip delivery into liver. At the same time we assessed the biological safety of turnip nanoparticle. Thioacetamide (TAA) induced hepatic nodular formation and fibrosis (mean of fibrosis score: 4). However, 1% turnip nanoparticle inhibited TAA-induced hepatic nodular formation and fibrosis (mean of fibrosis score: 2-3). Activities of serum enzymes (aspartic acid transaminase (AST), alanine transaminase (ALT), and total bilirubin (T-Bil)), complete blood count (CBC), and the appearance of organs were not different from control and 1% turnip nanoparticle treatment. Conclusively 1% turnip nanoparticle significantly reduced TAA-induced hepatic fibrosis and was safe in 7-weeks feeding.