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1.
J Cancer ; 6(1): 1-8, 2015.
Article in English | MEDLINE | ID: mdl-25553083

ABSTRACT

The objective of this study was to determine a chemopreventive activity of Korean red ginseng extract (KRG) in diethylnitrosamine (DEN) induced hepatocarcinogenesis in rats. After acclimatization for a week, Sprague-Dawley rats were randomized into five groups (n = 15) and fed either KRG (0.5, 1 or 2%) or control diets for 10 weeks. After two weeks of starting of experimental diets, the rats were initiated hepatocarcinogenesis by injection of DEN and were then subjected to two-thirds partial hepatectomy at five-week for developing the medium-term bioassay system. Both 0.5 and 1% KRG diets suppressed the area (55 and 60%; p= 0.0251 and 0.0144) and number (39 and 59%; p= 0.0433 and 0.0012) of glutathione S-transferase placental form (GST-P) positive foci when compared to the DEN-control group. The production of thiobarbituric acid reactive substances (TBARS) was significantly reduced in 0.5 and 1% KRG-treated rats. The supplementation of 1% KRG diet significantly elevated the levels of total glutathione (tGSH) and glutathione-related enzymes including cytosolic glutathione S-transferase (GST) and glutathione peroxidase (GPx) activities. It was also observed in cDNA microarray that the gene expressions (Cyp2c6, Cyp2e1, Cyp3a9, and Mgst1) involved in the xenobiotics metabolism via cytochrome P450 signaling pathway were down-regulated in the 1% KRG diet-treated group when compared to the DEN-control. The chemopreventive effects of KRG could be affected by 1) the decrease of lipid peroxidation, 2) the increase of tGSH content and GSH-dependent enzyme activities, and 3) the decrease of the gene expression profile involved in cytochrome P450 signaling pathway. These results suggest that KRG may prove to be a therapeutic agent against hepatocarcinogenesis.

2.
Nutr Res ; 33(9): 753-60, 2013 Sep.
Article in English | MEDLINE | ID: mdl-24034575

ABSTRACT

It has been proposed that ginseng has chemopreventive effects against several types of cancer in animals and humans. However, the mechanisms underlying the chemopreventive activities of fresh ginseng against hepatocarcinogenesis have not yet been elucidated. Therefore, we hypothesized that these ginseng species may prevent hepatocarcinogenesis but that the chemopreventive mechanisms may differ by species. To determine the chemopreventive and therapeutic potential of 3 different types of fresh ginseng on hepatocarcinogenesis, Sprague-Dawley rats were injected with diethylnitrosamine and fed diets containing 2% Panax japonicus CA Meyer (JN), P. quinquefolius L (QQ), or P. ginseng CA Meyer (GS) for 10 weeks. Glutathione S-transferase P form (GST-P)-positive foci, a stable marker for rat hepatocarcinogenesis, were shown in all carcinogen-injected rats; but only the GS diet significantly reduced the area and number (62% and 68%, respectively; P < .05) of GST-P-positive foci compared with the diethylnitrosamine control group. In addition, the number of proliferating cell nuclear antigen-positive hepatocytes in the GST-P-positive area was significantly decreased in the GS group but not in the JN or QQ groups. Using cDNA microarray analyses to investigate the underlying molecular mechanisms, we observed that the p53 signaling pathway was altered by the GS diet and that the expression of Cyclin D1, Cyclin G1, Cdc2a, and Igf-1, which are involved in the p53 signaling pathway, was downregulated by the GS diet. Our data demonstrate, for the first time, that GS, but not JN or QQ, induces cell cycle arrest in hepatocarcinogenesis. This study suggests that fresh GS has potential chemopreventive effects and may prove to be a therapeutic agent against hepatocarcinogenesis.


Subject(s)
Anticarcinogenic Agents/pharmacology , Cell Proliferation/drug effects , Liver Neoplasms, Experimental/drug therapy , Panax/chemistry , Plant Extracts/pharmacology , Animals , Cyclin D1/genetics , Cyclin D1/metabolism , Cyclin G1/genetics , Cyclin G1/metabolism , Diethylnitrosamine/toxicity , Dose-Response Relationship, Drug , Down-Regulation , Glutathione Transferase/metabolism , Hepatocytes/drug effects , Hepatocytes/metabolism , Hepatocytes/pathology , Insulin-Like Growth Factor I/genetics , Insulin-Like Growth Factor I/metabolism , Liver/drug effects , Liver/metabolism , Male , Oligonucleotide Array Sequence Analysis , Organ Size/drug effects , Proliferating Cell Nuclear Antigen/genetics , Proliferating Cell Nuclear Antigen/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
3.
J Med Food ; 12(2): 292-7, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19459728

ABSTRACT

The present study was conducted to examine the antidiabetic effects of two dietary dosages (0.5% and 2.0%) of freeze-dried Korean traditional Baechu (Chinese cabbage) kimchi in a high-fat (HF) diet-fed, streptozotocin (STZ)-induced type 2 diabetes (T2D) rat model. Five-week-old male Sprague-Dawley rats were fed HF diet for 2 weeks and then randomly divided into four groups of eight animals: normal control (NC), diabetic control (DBC), kimchi low (KML) (0.5%), and kimchi high (KMH) (2.0%) groups. Diabetes was induced by an intraperitoneal injection of STZ (40 mg/kg of body weight) in all groups except the NC group. After 4 weeks of feeding of experimental diets, serum insulin concentrations and Homeostatic Model Assessment pancreatic beta-cell function were increased and blood glycated hemoglobin was decreased in the kimchi-fed groups compared to the DBC group, while a significant (P < .05) difference was observed only in the KMH group for serum insulin concentration. Lower fasting blood glucose and better glucose tolerance were observed in the KMH group compared to the DBC and KML groups; however, differences were not significant. Food intake, body weight gain, Homeostatic Model Assessment insulin resistance index, and serum lipid profiles were not significantly influenced by kimchi-containing diets. Data of this study suggest that dietary Baechu kimchi has some antidiabetic effects even when fed with a HF-containing diet. Better results are possible if it is consumed with normal or low-fat rather than HF-containing diet.


Subject(s)
Brassica , Diabetes Mellitus, Experimental/therapy , Hypoglycemic Agents/pharmacology , Animals , Blood Glucose/metabolism , Diet , Dietary Fats/administration & dosage , Fermentation , Glucose Tolerance Test , Glycated Hemoglobin/metabolism , Insulin/blood , Insulin-Secreting Cells/drug effects , Korea , Lipids/blood , Liver/anatomy & histology , Male , Organ Size , Random Allocation , Rats , Rats, Sprague-Dawley
4.
Ann Nutr Metab ; 53(1): 6-12, 2008.
Article in English | MEDLINE | ID: mdl-18772584

ABSTRACT

BACKGROUND/AIMS: The present study was conducted to investigate the effects of two dietary doses of freeze-dried onion powder on diabetes-related symptoms in a high-fat (HF) diet streptozotocin (STZ)-induced diabetes rat model. METHODS: Five-week-old male Sprague-Dawley rats were fed a HF diet for 2 weeks and then randomly divided into 4 groups as follows: HF control (HFC), diabetic control (DBC), onion low (ONL; 0.5%) and onion high (ONH; 2.0%). Diabetes was induced by an intraperitoneal injection of STZ (40 mg/kg body weight) in all groups except the HFC group. RESULTS: After 4 weeks on the experimental diets, fasting blood glucose levels for both onion-fed groups were higher than in the DBC and HFC groups, albeit only significantly so (p < 0.05) in the ONL group. Serum insulin concentrations and insulin resistance were dose-dependently increased (however, not significantly so) in the onion-fed groups compared to the DBC group. Pancreatic beta-cell function and liver glycogen concentrations were nonsignificantly higher in the DBC and ONH groups compared to the ONL group. Additionally, the ONH group had significantly higher lipid concentrations (except for high-density lipoprotein cholesterol) compared to all other groups. The ONL group showed a similar hyperlipidemic trend, however to a lesser extent, with only triglycerides significantly differing from those of the DBC and HFC groups. CONCLUSION: The results suggest that the HF onion diet may increase insulin secretion and consequently insulin resistance in a dose-dependent manner, resulting in a worsened hyperglycemic and hyperlipidemic diabetic state. We conclude that higher dietary fat may impair the antidiabetic effects of dietary onion intake as has been previously reported.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Dietary Fats/administration & dosage , Insulin Resistance , Insulin/metabolism , Onions/chemistry , Plant Extracts/pharmacology , Animals , Blood Glucose/analysis , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/blood , Dietary Fats/adverse effects , Dietary Fats/pharmacology , Disease Models, Animal , Dose-Response Relationship, Drug , Freeze Drying , Injections, Intraperitoneal , Insulin/blood , Insulin Secretion , Lipids/blood , Liver/drug effects , Liver/metabolism , Liver Glycogen/analysis , Liver Glycogen/metabolism , Male , Plant Extracts/antagonists & inhibitors , Random Allocation , Rats , Rats, Sprague-Dawley
5.
Phytother Res ; 22(8): 1025-9, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18668490

ABSTRACT

The present study was conducted to clarify whether a low or a high, but tolerable, dietary dose of red chilli (RC) can ameliorate the diabetes related complications in a high-fat (HF) diet-fed streptozotocin (STZ)-induced type 2 diabetes model of rats. Five-week-old male Sprague Dawley rats were fed a HF diet for 2 weeks then randomly divided into four groups namely: normal control (NC), diabetic control (DBC), red chilli low (RCL, 0.5%) and red chilli high (RCH, 2.0%) groups. Diabetes was induced by an intraperitoneal (i.p.) injection of STZ (40 mg/kg BW) in all groups except the NC group. After 4 weeks feeding of experimental diets, the fasting blood glucose concentrations in both RC fed groups were not significantly different. The serum insulin concentration was significantly (p < 0.05) increased in the RCH group compared with the DBC and RCL groups. Blood HbA1c, liver weight, liver glycogen and serum lipids were not influenced by the feeding of RC-containing diets. The data of this study suggest that 2% dietary RC is insulinotropic rather than hypoglycemic at least in this experimental condition.


Subject(s)
Capsicum/chemistry , Diabetes Mellitus, Experimental/diet therapy , Diabetes Mellitus, Type 2/diet therapy , Hypoglycemic Agents/pharmacology , Insulin/physiology , Plant Extracts/pharmacology , Animal Feed , Animals , Blood Glucose/analysis , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Type 2/blood , Diet , Dietary Fats , Disease Models, Animal , Dose-Response Relationship, Drug , Food Deprivation/physiology , Glucose Tolerance Test , Glycated Hemoglobin/analysis , Hypoglycemic Agents/classification , Insulin/blood , Liver/drug effects , Liver/metabolism , Liver/pathology , Liver Glycogen/analysis , Liver Glycogen/metabolism , Male , Organ Size/drug effects , Plant Extracts/classification , Rats , Rats, Sprague-Dawley
6.
J Med Food ; 11(1): 152-9, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18361751

ABSTRACT

To compare the anti-diabetic effects of dietary ginger and garlic, 5-week-old male Sprague-Dawley rats were fed a high-fat (HF) diet (22% fat) for 2 weeks and then randomly divided into six groups of eight animals: Normal Control (NC), Diabetic Control (DBC), Ginger Low (GNL), Ginger High (GNH), Garlic Low (GRL), and Garlic High (GRH) groups. "Low" and "High" indicate addition of 0.5% and 2.0% freeze-dried ginger or garlic powder in their respective diets. Diabetes was induced by an intraperitoneal injection of streptozotocin (40 mg/kg of body weight) in all groups except the NC group. After 4 weeks of feeding of experimental diets, food intake was significantly (P < .05) higher in the GRL group compared to the GRH group. Serum insulin concentrations were significantly higher in the NC and GNH groups compared to the DBC, GNL, and GRL groups, while no significant difference was observed for the GRH group. Better glucose tolerance was observed in the GNH group compared to the DBC and all other ginger- and garlic-fed groups. Final body weight, fasting blood glucose, blood glycated hemoglobin, liver weight, liver glycogen levels, and serum lipid profiles were not influenced by the ginger- or garlic-containing diet. Data of this study suggest that ginger and garlic are insulinotropic rather than hypoglycemic while overall anti-diabetic effects of ginger are better than those of garlic, at least in this experimental condition. Much better anti-diabetic effects of ginger and garlic may be obtained when feeding is with a normal rather than a HF-containing diet.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Diet , Garlic , Hypoglycemic Agents/administration & dosage , Phytotherapy , Zingiber officinale , Animals , Blood Glucose/analysis , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/etiology , Dietary Fats/administration & dosage , Fasting , Food Preservation , Freeze Drying , Garlic/chemistry , Zingiber officinale/chemistry , Glucose Tolerance Test , Hemoglobins , Insulin/blood , Lipids/blood , Male , Peptide Fragments/blood , Rats , Rats, Sprague-Dawley
7.
Nutr Res Pract ; 2(4): 234-9, 2008.
Article in English | MEDLINE | ID: mdl-20016724

ABSTRACT

The purpose of this study was to investigate the effects of green tea ingestion on hepatocarcinogenesis before and after its initiation. Male Sprague-Dawley rats were fed an AIN76A diet with or without green tea. Initiation was induced by a single dose (200 mg/kg) of diethylnitrosamine at week 4 and 0.02% (w/w) 2-acetylaminofluorene was supplied in the diets. The control group had free access to water for 13 weeks (CTR13). Tea infusion was provided from the beginning of the experiment for 13 weeks (PRE13) or from the post-initiation stage until week 13 (POST13). Three other groups (CTR24, PRE24 and POST24) were added to examine the longer-term effects (24 weeks) with the same experimental design. The percentage area of liver sections that were positive for hepatic placental glutathione S-transferase (GST-P), which was used as a marker of preneoplastic lesions, was smaller in PRE13 (20.2 +/- 5.0%, mean +/- SD) and POST13 (26.0 +/- 4.8%) than in CTR13 (33.2 +/- 5.8%, p<0.05). Over the longer period, the GST-P lesions were significantly smaller for both PRE24 and POST24 (21.6 +/- 8.5% and 22.2 +/- 4.0%, respectively) than for CTR24 (28.6 +/- 5.1%, p<0.05), but there was no significant difference between PRE24 and POST24. The liver content of thiobarbituric acid reactive substances was significantly lower in the tea groups than in the controls (p<0.05). However, no significant differences were observed among groups of GST activity. The results show that tea consumption exhibits a stronger short-term initiation-inhibiting ability in liver carcinogenesis, but over a longer period, the preventive effects of green tea ingestion do not differ in post- and pre-initiation.

8.
Nutr Res Pract ; 2(2): 80-4, 2008.
Article in English | MEDLINE | ID: mdl-20126370

ABSTRACT

Beneficial effects of dehydroepiandrosterone (DHEA) supplement on age-associated chronic diseases such as cancer, cardiovascular disease, insulin resistance and diabetes, have been reported. However, its mechanism of action in hepatocellular carcinoma in vivo has not been investigated in detail. We have previously shown that during hepatocellular carcinogenesis, DHEA treatment decreases formation of preneoplastic glutathione S-transferase placental form-positive foci in the liver and has antioxidant effects. Here we aimed to determine the mechanism of actions of DHEA, in comparison to vitamin E, in a chemically-induced hepatocellular carcinoma model in rats. Sprague-Dawley rats were administered with control diet without a carcinogen, diets with 1.5% vitamin E, 0.5% DHEA and both of the compounds with a carcinogen for 6 weeks. The doses were previously reported to have anti-cancer effects in animals without known toxicities. With DHEA treatment, cytosolic malate dehydrogenase activities were significantly increased by ~5 fold and glucose 6-phosphate dehydrogenase activities were decreased by ~25% compared to carcinogen treated group. Activities of Se-glutathione peroxidase in the cytotol was decreased significantly with DHEA treatment, confirming its antioxidative effect. However, liver microsomal cytochrome P-450 content and NADPH-dependent cytochrome P-450 reductase activities were not altered with DHEA treatment. Vitamin E treatment decreased cytosolic Se-glutathione peroxidase activities in accordance with our previous reports. However, vitamin E did not alter glucose 6-phosphate dehydrogenase or malate dehydrogenase activities. Our results suggest that DHEA may have decreased tumor nodule formation and reduced lipid peroxidation as previously reported, possibly by increasing the production of NADPH, a reducing equivalent for NADPH-dependent antioxidant enzymes. DHEA treatment tended to reduce glucose 6-phosphate dehydrogenase activities, which may have resulted in limited supply for de novo synthesis of DNA via inhibiting the hexose monophophaste pathway. Although both DHEA and vitamin E effectively reduced preneoplastic foci in this model, they seemed to function in different mechanisms. In conclusion, DHEA may be used to reduce hepatocellular carcinoma growth by targeting NADPH synthesis, cell proliferation and anti-oxidant enzyme activities during tumor growth.

9.
Biofactors ; 29(1): 45-53, 2007.
Article in English | MEDLINE | ID: mdl-17611293

ABSTRACT

Present study was conducted to clarify whether lower or higher dietary dose of green tea is beneficial for the reduction of risk of type 2 diabetes. Five weeks old male SD rats were fed high fat diet for 2 weeks then divided into 4 groups of 8 animals as Normal Control (NC), Diabetic Control (DBC), Green Tea Low (GTL, 0.5%, Green Tea High (GTH, 2.0%) groups. Diabetes was induced by intra-peritoneal (i.p) injection of STZ (40 mg/kg BW) in all animals except NC group. After 4 weeks feeding of experimental diets, serum fasting blood glucose was not decreased but relatively increased in both green tea fed groups compared to DBC group. Serum insulin concentration was significantly (p< 0.05) increased in GTL group but not in GTH group when compared with DBC group. Serum lipids were significantly decreased in GTH group but not in GTL group compared to DBC group. Intra-peritoneal glucose tolerance test, blood HbA1c, liver weight, and liver glycogen level were not influenced by the feeding of green tea containing diets. Data of this study suggest that lower dose of green tea is insulinotropic when higher dose is hyperglycemic but hypolipidemic at least in this experimental condition.


Subject(s)
Diabetes Mellitus, Experimental/prevention & control , Diabetes Mellitus, Type 2/prevention & control , Plant Extracts/pharmacology , Tea/chemistry , Animals , Blood Glucose/analysis , Body Weight/drug effects , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/physiopathology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/physiopathology , Dietary Fats/administration & dosage , Dietary Fats/pharmacology , Dose-Response Relationship, Drug , Glucose Tolerance Test , Liver/drug effects , Liver/pathology , Male , Organ Size/drug effects , Plant Extracts/administration & dosage , Rats , Rats, Sprague-Dawley , Triglycerides/blood
10.
Pharmacology ; 79(4): 243-9, 2007.
Article in English | MEDLINE | ID: mdl-17457033

ABSTRACT

Seven-week-old male Sprague-Dawley (SD) rats were divided into six groups (LFC, LFD, HFC, HFD30, HFD40, HFD50) to determine whether animals receiving a low-fat (LF) diet plus nicotinamide-streptozotocin (NA-STZ) injection or animals receiving a high-fat (HF) diet plus STZ injection provide a better model of type 2 diabetes. After 2 weeks of feeding, diabetes was induced by intraperitoneal injection of NA (230 mg/kg BW) and STZ (65 mg/kg BW) in LFD, and STZ 30, 40, 50 mg/kg BW to HFD30, HFD40, HFD50 groups, respectively. Fasting blood glucose at 48-72 h and nonfasting blood glucose at 1 week after STZ injection were >200 and >600 mg/dl, respectively, in HFD40 and HFD50 groups while no significant difference was observed among other groups. Serum insulin concentration was significantly (p < 0.05) decreased in LFD, HFC, HFD30, and HFD40 groups compared to LFC and HFD50 groups. One animal died and other animals of the HFD50 group were in a critical condition. Serum lipid and liver glycogen were increased in HFD groups compared to other groups. The results of this study suggest that the HF diet-fed, 40-mg/kg BW STZ-injected SD rat is better than the LF diet-fed NA-STZ-injected rat as an animal model of human type 2 diabetes.


Subject(s)
Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Animals , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Type 2/chemically induced , Dietary Fats , Male , Niacinamide , Rats , Rats, Sprague-Dawley , Streptozocin
11.
Life Sci ; 77(12): 1293-306, 2005 Aug 05.
Article in English | MEDLINE | ID: mdl-15894339

ABSTRACT

The effect of dietary polyunsaturated fatty acids (PUFA) on hepatic peroxisomal oxidation was investigated with respect to the postprandial triacylglycerol levels. Male Sprague--Dawley rats were fed semipurified diets containing either 1% (w/w) corn oil, or 10% each of beef tallow, corn oil, perilla oil, and fish oil for 4 weeks and 4 days. Hepatic and plasma triacylglycerol levels were reduced in rats fed fish and perilla oil diets compared with corn oil and beef tallow diets. The peroxisomal beta-oxidation, catalase activity, and acyl-CoA oxidase (AOX) activity were markedly increased by fish oil feeding. To a lesser extent, perilla oil elevated AOX activity in a 4-day feeding although the effect gradually decreased in a 4-week feeding. Similarly, the mRNA levels were increased in rats fed fish and perilla oils. AOX activity was negatively correlated with postprandial triacylglycerol levels. In addition, the stimulation of AOX was highly associated with the content of long chain n-3 PUFA such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in hepatic microsome. These effects were evident within 4 days of initiating feeding. Therefore, alpha-linolenic perilla oil exerts a similar effect to fish oil in stimulating hepatic activity and gene expression of AOX by enriching long chain n-3 PUFA in hepatic membrane fraction, which can partly account for the reduction of postprandial triglyceridemia.


Subject(s)
Acyl-CoA Oxidase/metabolism , Plant Oils/pharmacology , Triglycerides/blood , alpha-Linolenic Acid/pharmacology , Animals , Blotting, Northern , Body Weight/drug effects , Catalase/metabolism , Diet , Dietary Fats/pharmacology , Fatty Acids/metabolism , Liver/drug effects , Liver/enzymology , Liver/metabolism , Male , Membrane Lipids/metabolism , Organ Size/drug effects , Oxidation-Reduction , RNA, Messenger/biosynthesis , Rats , Rats, Sprague-Dawley
12.
Asian Pac J Cancer Prev ; 6(1): 41-7, 2005.
Article in English | MEDLINE | ID: mdl-15780031

ABSTRACT

Chemoprevention is considered a rational strategy for dietary approaches to prevention of cancer. Multiple lines of evidence suggest that many of our dietary principles are able to intervene in the multistage carcinogenesis process and phytic acid (inositol hexaphosphate, IP6), a phytochemical present in a variety of plant species, has been shown to prevent various cancers, including those of the mammary gland, colon and liver. However, the mechanism of chemoprevention by IP6 has not been fully elucidated. In the present study, we examined the effects of inositol and/or IP6 supplementation on rat hepatocarcinogenesis initiated by diethylnitrosamine (DEN) and promoted by partial hepatectomy (PH). Supplementation with either inositol or IP6, or their combination, starting one week prior to administration of DEN, resulted in a significant decrease in both the area and the number of placental glutathione S-transferase positive (GST-P+) foci, a preneoplastic marker for DEN-initiated hepatocarcinogenesis. The administration of inositol and/or IP6 in drinking water caused marked enhancement in the glutathione S-transferase (GST) activity. In addition, the production of thiobarbituric acid reactive substances and the catalase activity were significantly reduced in rats supplemented with inositol and /or IP6. Based on these findings, it is likely that the chemopreventive effects of inositol and/or IP6 on rat hepatocarcinogenesis initiated by DEN and promoted by PH are associated with induction of GST activity and suppression of lipid peroxidation.


Subject(s)
Inositol Phosphates/pharmacology , Inositol/pharmacology , Liver Neoplasms, Experimental/prevention & control , Administration, Oral , Analysis of Variance , Animals , Diethylnitrosamine , Glutathione Transferase/metabolism , Inositol/administration & dosage , Inositol Phosphates/administration & dosage , Liver/drug effects , Liver/metabolism , Liver/pathology , Liver Neoplasms, Experimental/chemically induced , Male , Placenta/enzymology , Rats , Rats, Sprague-Dawley
13.
J Nutr Biochem ; 15(8): 485-92, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15302084

ABSTRACT

This study was performed to determine the effects of dietary perilla oil, a n-3 alpha-linolenic acid (ALA) source, on hepatic lipogenesis as a possible mechanism of lowering triacylglycerol (TG) levels. Male Sprague-Dawley rats were trained for a 3-hour feeding protocol and fed one of five semipurified diets as follows: 1% (w/w) corn oil control diet, or one of four diets supplemented with 10% each of beef tallow, corn oil, perilla oil, and fish oil. Two separate experiments were performed to compare the effects of feeding periods, 4 weeks and 4 days. Hepatic and plasma TG levels were decreased in rats fed perilla oil and fish oil diets, compared with corn oil and beef tallow diets. The activities of hepatic lipogenic enzymes such as fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase, and malic enzyme were suppressed in the fish oil, perilla oil, and corn oil-fed groups, and the effect was the most significant in the fish oil-fed group. Also, the activities of glycolytic enzymes, glucokinase, and L-pyruvate kinase showed the similar trend as that of lipogenic enzymes. The activity of FAS, the key regulatory enzyme in lipogenesis, was positively correlated with hepatic and plasma TG levels and reduced significantly in the perilla oil-fed group compared with corn oil-fed group. In addition, the FAS activity was negatively correlated with the hepatic microsomal content of EPA and DHA. In conclusion, suppression of FAS plays a significant role in the hypolipidemic effects observed in rats fed ALA rich perilla oil and these effects were associated with the increase of hepatic microsomal EPA and DHA contents.


Subject(s)
Fatty Acid Synthases/drug effects , Liver/enzymology , Plant Oils/pharmacology , Triglycerides/blood , alpha-Linolenic Acid/pharmacology , Animals , Body Weight/drug effects , Cell Membrane/chemistry , Cell Membrane/drug effects , Corn Oil/pharmacology , Dietary Fats/pharmacology , Eating/drug effects , Fatty Acid Synthases/genetics , Fatty Acid Synthases/metabolism , Fatty Acids/analysis , Fish Oils/pharmacology , Gene Expression Regulation/drug effects , Glucokinase/drug effects , Glucokinase/metabolism , Liver/drug effects , Male , Pyruvate Kinase/drug effects , Pyruvate Kinase/metabolism , Rats , Rats, Sprague-Dawley
14.
Obes Res ; 12(3): 445-53, 2004 Mar.
Article in English | MEDLINE | ID: mdl-15044661

ABSTRACT

OBJECTIVE: The prevalence of overweight, obesity, and metabolic disorders and their relationship with BMI were studied in South Korean adults. The appropriate BMI categories for overweight and obesity for Koreans were evaluated. RESEARCH METHODS AND PROCEDURES: The 1998 Korea National Health and Nutrition Examination Survey was the first such survey, to our knowledge, conducted on a cross-sectional and nationally representative population. The survey provided data on body weight; height; fasting serum glucose; triacylglycerol; total, low-density lipoprotein, and high-density lipoprotein cholesterol; blood pressure; and various other questions that were incorporated into this study. A total of 39,060 persons over the age of 1 year from 12,283 households participated in the Health and Nutrition Interview Survey. Of these, 10,876 people over the age of 10 years old participated in the Health Examination. We analyzed data from 7962 adults over the age of 20 years old. RESULTS: The overweight (BMI, >/=25.0 to <30.0) and obesity (BMI, >/=30) rates were low among Korean adults: 23.4% and 1.7% in men and 24.9% and 3.2% in women, respectively. However, the prevalences of diabetes, hypertension, and abnormal concentrations of serum triacylglycerol and total, low-density lipoprotein, and high-density lipoprotein cholesterol were high at 10.5%, 27.1%, 29.0%, 34.5%, 28.4%, and 37.4%, respectively. These disorders were age dependent, and, in general, there was a strong linear relationship between BMI and the disorders. The relative risk of disorders doubled at a BMI of 23.0 to 24.0 and tripled at a BMI of 26.0, compared with a baseline BMI of 18.5 to 22.0. DISCUSSION: High rates of diabetes, hypertension, and dyslipidemia were noted in middle-aged and elderly Koreans even at relatively low BMI. It might be appropriate to lower the BMI classification from the current >/=25.0 for overweight and >/=30.0 for obesity for this group of Koreans.


Subject(s)
Body Mass Index , Diabetes Mellitus/epidemiology , Hyperlipidemias/epidemiology , Hypertension/epidemiology , Obesity/epidemiology , Age Factors , Alcohol Drinking , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Exercise , Female , Health Surveys , Humans , Korea/epidemiology , Male , Middle Aged , Nutrition Surveys , Sex Factors , Smoking/epidemiology , Triglycerides/blood
15.
Exp Mol Med ; 35(5): 371-8, 2003 Oct 31.
Article in English | MEDLINE | ID: mdl-14646590

ABSTRACT

This study was conducted to examine the effects of dietary grape extracts on preneoplastic foci formation in rat hepatocarcinogenesis, and related hepatic enzymes. Male Sprague-Dawley rats were fed basal diet or grape diet containing 15% concentrated grape extracts (68 bricks). The grape diet groups were divided into whole-period grape diet group (DEN-GW; grape diet group fed throughout experimental period) and postinitiation grape diet group (DEN-GP; grape diet group fed from post initiation stage) according to the starting time point of the grape diet. Hepatocarcinogenesis was induced by diethylnitrosamine (DEN; 200 mg/kg bw) and 2/3 partial hepatectomy (DEN-B; DEN-treated basal diet group, DEN-GW, and DEN-GP groups), while the control group treated with saline and sham operation (Control group). The formation of placental glutathione (GSH) S-transferase positive (GST-P+) foci in DEN-GW group was moderately but significantly suppressed, however, not in DEN- GP group. Thiobarbituric acid reactive substances content of DEN-GW group was significantly lower than that of DEN-B group. The activity of fatty acid synthase (FAS) in the grape diet groups was decreased about 1/2 of the DEN-B group. The content of GSH and GSH peroxidase activity were increased by carcinogen treatment, but not modulated by grape diet. The activities of GSH S-transferase, p-nitrophenol hydroxylase, and catalase were not affected by diet or treatment. Conclusively, the grape diet-induced reduction of FAS activity that was expressed highly in neoplastic tissues, might be one of the contributing mechanisms of hepatic cancer prevention.


Subject(s)
Cell Transformation, Neoplastic/drug effects , Diet , Fatty Acid Synthases/metabolism , Liver/drug effects , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Vitis/chemistry , Administration, Oral , Animals , Body Weight/drug effects , Catalase/metabolism , Dietary Supplements , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Liver/enzymology , Liver/pathology , Liver Neoplasms/diet therapy , Liver Neoplasms/prevention & control , Male , Organ Size/drug effects , Rats , Rats, Sprague-Dawley
16.
Life Sci ; 73(19): 2515-26, 2003 Sep 26.
Article in English | MEDLINE | ID: mdl-12954459

ABSTRACT

This study was conducted to examine the effects of dietary garlic powder at the different levels on preneoplastic foci formation and glutathione (GSH)-dependent detoxifying enzyme activities in rat hepatocarcinogenesis. Male Sprague-Dawley rats were fed with garlic powder supplemented diets (0, 0.5, 2.0 or 5.0%) for 11 weeks, and induced hepatocarcinogenesis by diethylnitrosamine (DEN) and two-thirds partial hepatectomy in medium-term bioassay system. The 2.0 and 5.0% garlic powder diets suppressed the formation of placental GSH S-transferase positive (GST-P(+)) foci in number (49.7 and 63.1% of DEN-treated control group, respectively) and area (44.2 and 63.9% of DEN-treated control group, respectively). Total GSH content in 2.0% garlic powder diet group was 1.2 fold higher than that in DEN-treated control group. GSH S-transferase activity of 2.0% garlic powder diet group was lower than that in DEN-treated control group, and GSH peroxidase (GPx) activity was significantly increased by garlic powder diets (83 and 164% of DEN-treated control group, respectively). GSH reductase activity, however, did not show a noticeable difference among groups. Therefore, the suppression of GST-P(+) foci formation by garlic powder diets could be partly affected by the increase of total GSH content and GPx activity.


Subject(s)
Anticarcinogenic Agents/administration & dosage , Dietary Supplements , Garlic , Liver Neoplasms, Experimental/prevention & control , Animals , Diethylnitrosamine/toxicity , Glutathione Peroxidase/metabolism , Glutathione Transferase/metabolism , Lipid Peroxidation , Liver Neoplasms, Experimental/chemically induced , Liver Neoplasms, Experimental/enzymology , Male , Powders , Rats , Rats, Sprague-Dawley
17.
J Korean Med Sci ; 18(4): 547-51, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12923332

ABSTRACT

This short-term, prospective study was aimed to assess the effects of partially hydrolyzed formula (PHF) on the prevention of the development of atopic dermatitis in infants at high risk. The infants of parents with allergy symptoms and serum total IgE over 200 kU/L were divided into 3 groups by their feeding patterns: PHF group (n=15), standard formula (SF) group (n=32), and breast milk (BM) group (n=22). No allergenic food was given during the study period of 6 months, and breastfeeding mothers avoided egg ingestion. Their atopic symptoms were monitored every 2 months. The cumulative incidence and prevalence of atopic dermatitis at the age of 6 months were significantly less in the PHF group than in the SF group (47% vs. 78%, p<0.05; 20% vs. 59%, p<0.05). Those rates of the PHF group were also less than those of the BM group, but they were not statistically significant. There was no difference in the onset age and disease severity. These results suggest that early feeding of PHF to infants at high risk has a short-term preventive effect on the development of atopic dermatitis during the first 6 months of life. Long-term preventive effects should be evaluated.


Subject(s)
Dermatitis, Atopic/etiology , Dermatitis, Atopic/prevention & control , Infant Food , Protein Hydrolysates/therapeutic use , Breast Feeding , Electrophoresis, Polyacrylamide Gel , Female , Food Hypersensitivity , Humans , Hydrolysis , Hypersensitivity , Immunoglobulin E/blood , Infant , Infant, Newborn , Male , Milk, Human , Prospective Studies , Risk , Time Factors
18.
J Biochem Mol Biol ; 36(3): 258-64, 2003 May 31.
Article in English | MEDLINE | ID: mdl-12787479

ABSTRACT

This study examined the effect of dietary polyunsaturated fatty acids (PUFA) that were supplemented with vitamin E on lipid peroxidation, glutathione-dependent detoxifying enzyme system activity, and lipogenic fatty acid synthase (FAS) expression in rat liver. Male Sprague-Dawley rats were fed semipurified diets containing either 1% (w/w) corn oil or 10% each of beef tallow, corn oil, perilla oil, and fish oil for 4 wk. Alpha-tocopherol was supplemented in perilla oil (0.015%) and fish oil (0.019%). Hepatic thiobarbituric acid reactive substances, an estimate of lipid peroxidation, were not significantly different among the dietary groups. The glutathione peroxidase, glutathione reductase, and glutathione S-transferase activities were all elevated by the polyunsaturated fats, especially fish oil. The activity of FAS was reduced in the polyunsaturated fat-fed groups in the order of fish oil, perilla oil, and corn oil. The mRNA contents decreased in rats that were fed the 10% fat diets, particularly polyunsaturated fats, compared with the rats that were fed the 1% corn oil diet. Similarly, the inhibitory effect was the greatest in fish oil. These results suggest that lipid peroxidation can be minimized by vitamin E; PUFA in itself has a suppressive effect on lipogenic enzyme.


Subject(s)
Dietary Fats, Unsaturated/administration & dosage , Fatty Acid Synthases/antagonists & inhibitors , Lipid Peroxides/metabolism , Animals , Blotting, Northern , Corn Oil/administration & dosage , Enzyme Activation/drug effects , Fats/administration & dosage , Fatty Acid Synthases/genetics , Fatty Acid Synthases/metabolism , Fatty Acids/analysis , Fish Oils/administration & dosage , Gene Expression Regulation, Enzymologic/drug effects , Glutathione Peroxidase/metabolism , Glutathione Reductase/metabolism , Glutathione Transferase/metabolism , Lipid Metabolism , Lipid Peroxidation/drug effects , Liver/drug effects , Liver/enzymology , Male , Plant Oils/administration & dosage , RNA, Messenger/drug effects , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , alpha-Linolenic Acid/administration & dosage
19.
J Epidemiol ; 13(3): 162-8, 2003 May.
Article in English | MEDLINE | ID: mdl-12749604

ABSTRACT

BACKGROUND: The association of dietary habits and Helicobacter pylori infection with early gastric cancer is still unclear. METHODS: A hospital-based case-control study was conducted in Korea. Sixty-nine patients were newly diagnosed as having early gastric cancer at the Division of Gastroenterology, Asan Medical Center, and 199 healthy subjects who visited the Health Promotion Center of the this same hospital for annual health examinations were selected as controls. Helicobacter pylori infection status was assayed by ELISA, and information for dietary habits was obtained by interview using a semi-quantitative food frequency questionnaires. Preference for salty taste was also evaluated using a sensitive test. RESULTS: H. pylori seropositivity was observed in 88% of cases, as compared with 75% of controls (OR = 5.3, 95% confidence interval:1.7-16.5). Adaptive salt concentration was significantly and positively associated with early gastric cancer risk (p < 0.01). Decreased risks of early gastric cancer were observed in association with intakes of clear broth, raw vegetables, fruits, fruit or vegetable juices, and soybean curds. On the other hand, a high intake of salt-fermented fish and kimchi were associated with an elevated risk of early gastric cancer. Subjects with positive H. pylori infection and a high salty preference had a 10-fold higher risk of early gastric cancer than subjects without H. pylori infection and with a low salty preference (p for interaction = 0.047). CONCLUSION: Some dietary factors and H. pylori infection are significantly associated with early gastric cancer. In particular, high-salty diets may enhance the effect of H. pyori infection in gastric carcinogenesis.


Subject(s)
Diet/statistics & numerical data , Helicobacter Infections/epidemiology , Helicobacter pylori , Stomach Neoplasms/epidemiology , Adult , Age of Onset , Case-Control Studies , Female , Humans , Korea/epidemiology , Logistic Models , Male , Middle Aged , Odds Ratio , Risk Factors , Smoking/epidemiology , Sodium, Dietary
20.
J Biochem Mol Biol ; 35(6): 615-22, 2002 Nov 30.
Article in English | MEDLINE | ID: mdl-12470597

ABSTRACT

The purpose of this study was to determine the effects of dietary garlic powder on diethylnitrosamine (DEN)- induced hepatocarcinogenesis and cytochrome P450 (CYP) enzymes in weaning male Sprague-Dawley rats by using the medium-term bioassay system of Ito et al. The rats were fed diets that contained 0, 0.5, 2.0 or 5.0% garlic powder for 8 weeks, beginning the diets with the intraperitoneal (i.p.) injection of DEN. The areas of placental glutathione S-transferase (GST-P) positive foci, an effective marker for DEN-initiated lesions, were significantly decreased in the rats that were fed garlic powder diets; the numbers were significantly decreased only in the 2.0 and 5.0% garlic-powder diets. The p-Nitrophenol hydroxylase (PNPH) activities and protein levels of CYP 2E1 in the hepatic microsomes of the rats that were fed the 2.0 and 5.0% garlic powder diet were much lower than those of the basal-diet groups. Pentoxyresorufin O-dealkylase (PROD) activity and CYP 2B1 protein level were not influenced by the garlic-powder diets and carcinogen treatment. Therefore, the suppression of CYP 2E1 by garlic in the diet might influence the formation of preneoplastic foci during hepatocarcinogenesis in rats that are initiated with DEN.


Subject(s)
Anticarcinogenic Agents/pharmacology , Cytochrome P-450 CYP2E1/metabolism , Cytochrome P-450 CYP2E1/pharmacology , Diethylnitrosamine/pharmacology , Garlic/metabolism , Liver Neoplasms/chemically induced , Liver Neoplasms/prevention & control , Plant Extracts/pharmacology , Animals , Cytochrome P-450 CYP2B1/metabolism , Dose-Response Relationship, Drug , Glucose-6-Phosphatase/metabolism , Glutathione Transferase/metabolism , Immunoblotting , Immunohistochemistry , Liver Neoplasms/metabolism , Male , Rats , Rats, Sprague-Dawley
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