• Title/Summary/Keyword: Hepatocarcinogenesis

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STUDIES OF VARIOUS FACTORS ON INDUCTION OF EXPERMIMENTAL HEPATOCARCINOGENESIS IN SPRAUGE-DAWLEY RATS

  • Jeong, Ja-Young;Kim, Hyoung-Chin;Lee, Yong-Soon
    • Toxicological Research
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    • v.7 no.1
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    • pp.93-112
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    • 1991
  • This study was carried out to investigate the various factors on induction of experimental hepatocarcinogenesis in Sprauge-Dawley rats. The experimental animals were divided into three Experiment. Experiment I, II and III were began rats with initial age of 6, 16 and 55 weeks, respectively. All Experiment were injected intrapertioneal with diethylnitrosamine (DENA` 200 mg/kg) as an intiator and group 3, 4 of Experiment I, II and III were fed on diet containing 0.02% 2-acetylaminofluorene (2-AFF) as a promoter for 6 weeks. Three weeks after two-thirds partial hepatectomy was performed in group 2, 4 of Experiment I & II and group 3 of Experiment III.

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Effects of Dietary Garlic Powder on GST-P Positive Foci and Glucose 6-Phosphatase Activity in Diethylnitrosamine-Initiated Rat Hepatocarcinogenesis

  • Seo, Jeong-Min;Park, Kyung-Ae;Yeo, Eui-Zu;Choi, Hay-Mie
    • BMB Reports
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    • v.32 no.3
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    • pp.259-265
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    • 1999
  • This study was designed to examine the anticarcinogenic effect of dietary supplementation with garlic powder on rat hepatocarcinogenesis. All rats were initiated by a single dose (200 mg/body weight) intraperitoneal injection of diethylnitrosamine (DEN), and three weeks later, subjected to two-thirds partial hepatectomy. Two weeks after initiation, four groups of rats were given experimental diets supplemented with 0 (control group), 0.5, 2.0, or 5.0% garlic powder for 6 weeks. Rats were sacrificed at eight weeks after initiation. The induction of placental glutathione S-transferase (GST-P) positive foci was significantly inhibited almost equally in all three groups fed garlic diets. Glucose 6-phosphatase (G6Pase) activity was increased in rats fed 0.5% and 2.0% garlic powder, and was negatively correlated with the number and area of GST-P positive foci. Thiobarbituric acid reactive substance (TBARS) contents were decreased in rats fed 2.0% and 5.0% garlic powder. Only 5.0% garlic powder supplementation significantly increased the glutathione content and the glutathione S-transferase activity, compared to the control group. Therefore, all levels of garlic powder, 0.5% to 5.0%, exerted an anti promotional effect during hepatocarcinogenesis. Dietary supplementation with garlic powder seemed to maintain microsomal membrane integrity by increasing G6Pase activities. Glutathione-dependent detoxifying enzymes did not seem to contribute to this protective effect directly. The present study suggests that garlic powder is effective in inhibiting the induction of GST-P positive foci, possibly by stabilizing the hepatic microsomal membrane.

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Protective Effect of Soybean against Hepatocarcinogenesis Induced by DL-Ethionine

  • Aiad, Fatma;El-Gamal, Basiouny;Al-Meer, Jehan;El-Kerdasy, Zinab;Zakhary, Nadia;El-Aaser, Abdelbaset
    • BMB Reports
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    • v.37 no.3
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    • pp.370-375
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    • 2004
  • There has been increasing interest in the value of using soybean to delay or reduce the tumor incidence. This study was undertaken to investigate the possible protective effects of soybean against hepatocarcinogenesis induced by DL-ethionine. Accordingly, we measured biochemical changes occurring in serum and liver of rats treated with DL-ethionine in the presence or absence of soybean. Male albino rats were fed a control diet containing the hepatocarcinogen, DL-ethionine, or the control diet plus soybean 30%, or the control diet plus soybean plus DL-ethionine 0.25% for three months and then returned to a control diet for up to nine months. Rats fed a control diet plus DL-ethionine showed a gradual decrease in liver DNA, RNA, total protein, and liver weight and enzyme activites of liver transaminases (GOT and GPT) and alkaline phosphatase over the 7-month study period. This was followed by a large increase in the liver parameters at the end of the $9^{th}$ month, except for 5'-nucleotidase and glucose-6-phosphatase that showed a large decrease. On the other hand, a gradual increase in the serum enzyme activities of GOT, GPT, 5-nucleotidase, alkaline phosphatase, and in the albumin/globulin (A/G) ratio is observed in the group of rats fed a control diet plus DL-ethionine compared to the control group over 8 months, and this was followed by a large increase in all serum parameters studied at nine-months. The administration of 30% soybean to the rat diet in addition to DL-ethionine maintained all parameters studied at near control values until the end of the $9^{th}$ month. This study suggests that soybean has a protective effect against the hepatocarcinogenesis induced by DL-ethionine.

Suppression of Hepatic Lipogenic Enzyme by Dietary Fish Oil In Rat Hepatocarcinogenesis

  • Kim, Hye-Kyeong;Choi, Hay-Mie;,
    • Toxicological Research
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    • v.14 no.3
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    • pp.285-291
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    • 1998
  • This study was designed to examine the effects of polyundaturated fatty acid(PUFA) from different sourecs on hepatic lipogenic enzyme and peroxisomal ${\beta}$-oxidation in murine hepatocarcinogenesis initiated by diethylnitrodamine (DEN). Male Sprague-Dawley rats were fed one of three diets containing 10%(w/w)fat; fish oil-corn oil blended(FO), corn oil-beef tallow-fish oil blended(CF), or corn oil-beef tallow-perilla oil blended (CP), from the gestation period. At 10 weeks, animals were received a single inraperitoneal injection of DEN (200mg/kg body weight), were subjected to two-thirds partial hepatectomy 3 weeks later and were sacrificed 8 weeks after DEN initiation. The areas of placental glutathione S-transferase (GST-P) positive foci were significantly smaller in rats fed fish oil containing diets (FO and CF) than those fed CP diet. Fish oil feeding significantly decreased th activities of lipogenic enzyme. Rats fed fish oil containing diets (FO, CF) exhibited the lower fatty acid synthase (FAS) activity than those fed CP diet and FAS activity was positively correlated with areas of GSP-P positivie foci. Glucose-6-phophate dehydrogenase activity was the lowest and peroxisomal ${\beta}$-oxidation was stimulated in rats fed FO diet compared to other groups. It was also found that serum cholesterol was decreased in FO group. Therefore, the preventive effect against hepatocarcinogenesis and hypolipidemic effect of fish oil can be explained partly by suppression of the hepatic lipogenesis and by increase of peroxisomal ${\beta}$-oxidation.

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Effects of the Pilose Antler on the Experimental Hepatocarcino- genesis and the Natural Killer Cell Activity in Rats (랫드의 실험적 간암발생과 자연살해세포의 활성에 미치는 녹용의 효과)

  • 정자영;길광섭;이영순
    • Toxicological Research
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    • v.14 no.4
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    • pp.475-481
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    • 1998
  • This study was performed to investigate the modifying effect of the general (GPA) and the fermented pilose antler (FPA) on experimental hepatocarcinogenesis and Natural Killer cell activity in rats. Specific pathogen free, 5-week male Sprague-Dawley rats were divided into four groups. To induce hepatocarcinogenesis, diethylnitrosamine (DEN, 200 mg/kg, i.p.) was used as a tumor initiator and was given in a single dose at experimental onset. All rats were given a partial hepatectomy (PH) at 3 weeks after experimental onset. Sodium phenobarbital (PB, 0.05% in diet), GPA (0.075% in diet) and FPA (0. 075% in diet) were given from 2 to 8 weeks. Group I of the initiation control group was only given DEN. As initiation-promotion group, Group II was given DEN and then PB. Group III and IV were given DEN-PB-GPA and DEN-PB-FPA, respectively. In hematological analysis, as compared with Group I. the number of white blood cells were significantly increased in the GPA (p<0.01) and the FPA treated group (p<0.05), respectively. Natural killer (NK) cell activity by flow cytometer (FCM) analysis was higher in group of treated with the GPA (35%) than that of the FPA (27.5%), but not significant. Result of the immunohistochemical staining of the glutathione S-transferase placental form (GST-p) indicated that the number of and area of the pre-neoplastic lesions was not significantly changed in Group III and IV compared Group II, respectively. In conclusion, the GPA and the FPA treatment significantly increased the number od WBC in peripheral blood, but the enhancing NK activity and the modifying effect on the experimental hepatocarcinogenesis were not observed.

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Modification of Hepatic Microsomal Cytochrome P450 2E1 Enzyme by Garlic Powder in Rat Hepatocarcinogenesis

  • Park, Kyung-Ae;Choi, Hay-Mie
    • BMB Reports
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    • v.30 no.1
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    • pp.73-79
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    • 1997
  • This study was designed to investigate the effects of dietary garlic powder on cytochrome P450 enzymes and membrane stability in murine hepatocarcinogenesis initiated by diethylnitrosamine (DEN). Male Sprague-Dawley rats received a single intraperitoneal injection of DEN (200 mg/kg body wt) dissolved in saline. After 2 weeks on a basal diet, animals were fed diets containing 0. 0.5. 2.0. or 5.0% garlic powder for 6 weeks, and were subjected to two-thirds partial hepatectomy. The areas of placental glutathione S-transferase (GST-P) positive foci were inhibited in rats fed with garlic diets. GST-P is the most effective marker for DEN-initiated lesions. Hepatic microsomal lipid peroxidation was significantly decreased in rats fed with 2.0 and 5.0% garlic powder diets compared with that observed in the control animals and hepatic microsomal glucose 6-phosphatase (G6Pase) activity was found to increase significantly in rats fed 0.5 and 2.0% garlic powder diets. Thus as little as 0.5% garlic powder has a positive effect on the stability of hepatic microsomal membranes. p-Nitrophenol hydroxylase (PNPH) activity and the level of cytochrome P450 2E1 protein in the hepatic microsomes from rats fed diets containing 2.0 and 5.0% garlic powder were much lower than those of control microsomes. Rats fed 5.0% garlic powder diets exhibited the lowest P450 2E1 activity and protein levels among groups. Pentoxyresorufin O-dealkylase activity and immunoblot (cytochrome P450 2B1) analyses were not different between groups. However, the levels of cytochrome P450 1A1/2 protein in rats fed 0.5 and 2.0% garlic powder were significantly induced compared to controls. These results suggest that 2.0% garlic powder is effective in inhibiting the areas of GST-P positive foci, modulating certain isoforms of cytochrome P450 enzymes and stabilizing the hepatic microsomal membrane. Thus, the selective modification of cytochrome P450 enzymes and membrane stability by dietary garlic powder may influence areas of GST-P positive foci and chemoprevention of post-initiation of rat hepatocarcinogenesis.

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Effects of Vitamin E and Dehydroepiandrosterone on the Formation of Preneoplastic Lesions in Rat Hepatocellular Carcinogenesis (비타민 E와 Dehydroepiandrosterone이 화학적 발암원으로 유도한 쥐간의 전암성 병변에 미치는 영향)

  • Kim, Sook-Hee;Choi, Hay-Mie
    • Journal of Nutrition and Health
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    • v.38 no.5
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    • pp.364-372
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    • 2005
  • This study is designed to examine the effects of dietary supplementation with vitamin E and dehydroepiandrosterone (DHEA) on the formation of preneoplastic lesions in diethylnitrosamine (DEN) induced rat hepatocarcinogenesis. All Weaning male Sprague-Dawley rats were initiated by a single dose of DEN (200mg/kg body weight), subjected to two­thirds partial hepatectomy 3 weeks later and were sacrificed 8 weeks after DEN initiation. Two weeks after initiation, rats were fed Purina purified rodent diet 5053 (Ralston Purina Rat chow, USA) with $1.5\%$ (15,000 IU/kg diet) vitamin E, $0.5\%$ DHEA and both of those supplemented diet for 6 weeks. Placental glutathione S-transferase (GST-P) positive foci, the activities of catalase, total-glutathione peroxidase (GPx) , glutathione reductase (GR), glutathione S-transferase (GST) and thiobarbituric acid reactive substances (TBARS) contents were decreased significantly by vitaimin E supplement. On the other hand GST-P positive foci number, Cu/Zn-superoxide dismutase (SOD) and glucose 6-phosphatase (G6Pase) activities weren't changed by vitamin E supplement. It might suggest that protective effect of vitamin E against hepatocarcinogens is not involved in the formation of the GST-P positive foci but related to the expansion of that. It seemed that vitamin E supplement helped endogenous defense system in carcinogenesis by decreasing TBARS contents, $H_2O_2$, organic peroxides. Therefore, vitamin E seemed to protect cell from free radical damage in carcinogenesis. By DHEA supplement liver weight and liver/body ratio were increased, the area and number of GST-P positive foci, the activities of catalase, GR, total GPx, GST and the TBARS contents were decreased significantly. On the other hand Cu/Zn-SOD and G6Pase activities weren't changed by DHEA supplement. In hepatocarcinogenesis the activities of antioxidant enzymes weren't increased by DHEA supplement. DHEA did not increase the oxidative stress, while DHEA seems to have anticarcinogenic effect in rats hepatocarcinogenesis.

Effects of Sardine Oil Fedding and Vitamin E Supplementation on Histopathological Changes and $\alpha$-L-Fucosidase Activity in Experimental Hepatocarcinogenesis (정어리유 섭취와 비타민 E 보충이 실험적 간 발암과정의 병리조직학적 변화와 $\alpha$-L-fucosidase의 활성도에 미치는 영향)

  • 김정희;윤혜진
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.30 no.1
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    • pp.119-126
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    • 2001
  • Effects of Sardine Oil Feeding and Vitamin E Supplementation on Histopathological Changes and $\alpha$-L-fucosidase activity in experimental hepatocarcinogenesis. Sprague-Dawley rats weighing 80~90 g were fed the diet containing either 15% corn oil (CO) or sardine oil (SO) with or without vitamin E supplements (dl-$\alpha$-tocopherol acetate 800 IU/kg diet) for 8 weeks. After 2 weeks of feeding, the rats were given a single intraperitoneal injectin of diethylnitrosamine (DEN, 200 mg/kg BW). From the fifth week, rats were given 0.02% acetylaminofluorene (AAF) in diet for 4 weeks. At the seventh week, 0.05% phenobarbital in liver and hepatic glutathione S-transferase palcental form positive (GST-P+) foci were examined by Hematoxylin& Eosin (H&E) staining and immunohistochemical method, respectively. Serum $\alpha$-L-fucosidase activity was determined. The livers fromt he carcinogen treated rats showed significantly increased formation of GST-P+ foci at sacrifice points while the livers fromthe non-carcinogen treated groups showed almost no foci. Although GST-P+ foci formation was not affected by dietary oil, it was increased unexpectedly by vitamin E supplementation. Histopathological changes were similar to patterns of GST-P+ foci formation in almost all groups. Serum $\alpha$-L-fucosidase activities were increased by carcinogen treatment in all dietary groups. $\alpha$-L-fucosidase activities were positively correlated with GST-P+ foci formation. There results suggest that excessive vitamin E supplementation can enhance hepatocarcinogenesis although the mechanisms involved are not clearly understood.

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Effects of Vitamin E supplement and Perilla oil on the Cytochrome P-450 contents and Fatty acid composition in Rat Hepatocarcinogenesis

  • Kim, Sookhee;Jungin, Choi
    • Culinary science and hospitality research
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    • v.4
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    • pp.129-146
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    • 1998
  • The effects of vitamin E supplement on 15%(w/w diet) perilla or corn oils were studied in rat hepatocellular chemical carcinogenesis induced by modified Solt & Farber model, which consists of 20mg/kg body weight diethylintrosamine(DEN) injection, 3 weeks feeding of 0.02%2-acetylaminofluorene(2-AAF) and partial hepatectomy. The area of placental glutathione S-transferase(GST-P) positive foci tended to be smaller in perilla oil group had lower thiobarbituric acid reactive substances(TBARS) CONTENT. Fatty acid compositions in microsomal membrane were reflected by dietary fatty acid compositions, and not affected by carcinogen treatment or vitamin E supplement. By vitamin E supplement, linolenic acid contents of perilla oil group were much increased. By carcinogen treatment, membrane stability decreased significantly in corn oil, but maintained in perilla oil groups Vitamin E supplemental effect was noticed only in the corn-carcinogen group. Perilla oil may prevent hepatocarcinogenesis by maintaining membrane stability and by reducing cytochrome P-450 content. Vitamin E supplement did not seem to have the effect on hepatocarcinogenesis, but prevented lipid peroxidation, reduced cytochrome P-450 content and maintained membrane stability.

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Effects of γ-Irradiated Pork Diet on Cytochrome P-450 System, Microsome Glucose 6-Phosphatase Activity and Antioxidative Defense Systems in Rat Hepatocarcinogenesis

  • Kang, Il-Jun;Kim, Jung-Hee;Chung, Cha-Kwon
    • Preventive Nutrition and Food Science
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    • v.8 no.2
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    • pp.158-161
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    • 2003
  • This study investigated the effects of a ${\gamma}$-irradiated pork (0-30 kGy) diet on lipid peroxidation, cytochrome P-450 content, microsomal glucose 6-phosphatase (G-6-Pase) activity and antioxidative defense systems in diethylnitrosamine (DEN)-induced rat hepatocarcinogenesis. The body weight of rats fed irradiated diets did not change significantly. Liver weight was significantly increased by the administration of DEN, but not by irradiated diets at any dose level. There were no significant effects of gamma irradiation on the content of microsomal malondialdehyde (MDA), cytochrome P-450, or on the activity of G-6-Pase. However, with DEN treatment, cytochrome P-450 content was significantly increased while microsomal G-6-Pase activity was significantly decreased. The ${\gamma}$-irradiated diet supplement did not affect serum retinol or $\alpha$-tocopherol concentrations. However, it did cause a significant decrease in hepatic retinol at 30 kGy. With DEN treatment, hepatic retinol content was even more significantly (p<0.05) decreased compared to the non-irradiated control. The enzyme activities related to antioxidative defense systems, including glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rx) and glutathione S-transferase (GST) were not affected by gamma irradiation. Those results suggest that an irradiated pork diet up to 30 kGy may not cause a health hazard in experimental animals.