• Title/Summary/Keyword: Hepatocellular carcinogenesis

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The Effect of the Curcumae Longae Rhizoma (CLR) Extract on the Hepatocellular Carcinogenesis and Acute Liver Damage Induced by Diethylnitrosamine (DENA) and CCl4 in Rats (강황추출물이 Diethylnitrosamine과 CCl4로 유발된 흰쥐의 간암과 간 손상에 미치는 영향)

  • Jung, Tae-San;Choi, Chang-Won
    • Herbal Formula Science
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    • v.22 no.1
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    • pp.177-192
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    • 2014
  • Objective : In order to investigate the effect of Curcumae Longae Rhizoma(CLR) extract on the hepatocellular carcinogenesis and acute liver damage induced by diethylnitrosamine(DENA) and $CCl_4$ in rats. Methods : Experimental groups were subdivided into four; normal group (Nor), acute liver damage and hepatocellular cancer inducing control group (Con), and CLR extract 200mg/kg/day (CAA) or 400mg/kg/day (CAB) administered groups to Con. Thereafter the changes of the body weight, the liver weight and the weight of liver/100g body weight, total cholesterol, HDL cholesterol, triglyceride, the activities of AST, ALT, ALP, LDH, AFP, SOD, catalase were measured. And we observed by optical and electron microscopy. Result : 1. The body weight was decreased in Con compared with Nor for 5 weeks, but increased in Con compared with Nor from 6 week to 9 week. During experimental period of total 9 weeks, CAA and CAB were increased compared with Con. 2. The liver weight was increased significantly (p<0.05) in Con compared with Nor. The weight of liver/100g body weight was increased significantly (p<0.05) in Con compared with Nor and decreased significantly (p<0.05) in CAB compared with Con. 3. The level of total cholesterol was increased in Con and CAA compared with Nor, but there was not statistically significant. The level of triglyceride was decreased in Con compared with Nor. But increased in CAA and CAB compared with Con. The level of HDL-cholesterol was significantly increased (p<0.05) in CAA and CAB compared with Con. 4. The activities of AST, ALT were increased in Con compared with Nor, but decreased in CAA compared with Con, significantly decreased (p<0.05) in CAB compared with Con. 5. The activities of ALP, LDH were increased in Con compared with Nor, but decreased in CAA and CAB compared with Con. 6. The activities of AFP was increased significantly (p<0.05) in Con compared with Nor, but decreased significantly (p<0.05) in CAA and CAB compared with Con. 7. The activities of SOD were increased in Con, CAA and CAB compared with Nor, but decreased in CAA and CAB compared with Con. The activities of Catalase was more increased in CAA and CAB compared than Con. 8. The results of light microscopical observation, a number of hepatocytes were damaged in Con compared with Nor and CAB. 9. According to the electron microscopical observation, irregular nuclear membrane, condensed nucleoplasm was observed in Con, the experimental group was observed in the nucleus of the well-preserved and evenly developed nucleoplasm. Conclusions : These results suggest that administration of CLR extract suppress or retard on the hepatocellular carcinogenesis and acute liver damage induced by DENA and $CCl_4$ in rats.

The Effect of Injinsammul-tang(IJS) on the Hepatocellular Carcinogenesis Induced by Diethylnitrosamine(DENA) in Rats (인진삼물탕(茵蔯三物湯)이 DENA로 유발된 흰쥐의 간암에 미치는 영향)

  • Jung, Tae-San;Choi, Eun-Hee;Kang, Seong-Sun;Kim, In-Soo;Lee, Young-Soo;Choi, Chang-Won
    • The Journal of Internal Korean Medicine
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    • v.32 no.3
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    • pp.397-410
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    • 2011
  • Objectives : This study was designed to investigate the effect of Injinsammul-tang (IJS) on hepatocellular carcinogenesis in rats. Methods : Sprague Dawley (SD) rats of control and treatment groups received intraperitoneal injection of 50 mg/kg/day diethylnitrosamine (DENA) weekly for 8 weeks. Experimental rats were classified into 3 groups; normal group (Nor), hepatic cancer induced control group (Con), and IJS extract 250 mg/kg administered group (IST) after being injected with DENA. Thereafter the changes of body weight, liver weight and weight of liver/100g body weight, the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and superoxide dismutase (SOD) were measured. Gross anatomy and optical microscopy were also observed. Results : The body weight decreased in Con and IST compared with the Nor. The weight of liver and the weight of liver/100g body weight increased significantly in Con and IST compared with the Nor. The activities of AST, ALT, ALP, LDH increased in the Con compared with Nor, but decreased in IST compared with Con. The activities of SOD increased in the Con and IST compared with Nor. Upon naked eye and light microscopic examination, IJS improved the morphological and histopathological changes of liver caused by DENA-induced hepatic neoplasm. The number of hepatic p53 positive cells decreased in the IST compared with Con. Conclusions : Most of the results did not show a significant effect, but some of the results showed a significant effect. It can be estimated that IJS has some effects on hepatocellular carcinogenesis induced by DENA in rats, and further studies will be needed.

The Effect of the Keughachukeo-tang Extract on the Hepatocellular Carcinogenesis and Acute Liver Damage Induced by Diethylnitrosamine and CCl4 in Rats (膈下逐瘀湯이 Diethylnitrosamine과 CCl4로 유발된 흰쥐의 肝癌 形成과 肝損傷에 미치는 영향)

  • Heo, Rae-Kyong;Seung, Kee-Moon;Kim, So-Yeon;Je, Jun-tae;Kwon, So-yeon;Moon, Goo;Lee, Jong-Deok;Won, Jin-Hee
    • Journal of Pharmacopuncture
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    • v.12 no.4
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    • pp.63-76
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    • 2009
  • This study was performed to observe the effect of Keughachukeo-tang(KH) extract on the hepatocellular carcinogenesis and acute liver damage induced by Diethylnitrosamine(DENA) and $CCl_4$ in Rats. Experimental groups were divided into four; normal group(Nor), acute liver damage and hepatocellular cancer inducing control group(Con), KH extract 350㎎/㎏/day(KHA), and 700㎎/㎏/day(KHB) administered groups to Con. The results obtained are as follows: The body weight increased in KHA and KHB than Con from 7th week to the 8th week. The activities of Alanine aminotransferase(ALT) were the most increased in the Con among experimental group. The activities of aspartate aminotransferase(AST), alkaline phosphatase(ALP), and lactacte dehydrogenase(LDH) were significantly decreased(p$<$0.05) in the KHA and KHB compared with Con. Alpha fetoprotein(AFP) were the most increased in the Con among experimental groups. The activities of superoxide dismutase(SOD) were the most increased in the Con among experimental groups. The activities of catalase were significantly increased(p$<$0.05) in the KHA and KHB compared with Con. The results of light microscopical observation, a number of hepatocytes were damaged in the Con compared with Nor and KH extract administerd groups. The number of hepatic p53 positive cells was reduced in the KH extract administered groups compared with Con. These results suggest that administration of KH extract suppress or retard on the Hepatocellular Carcinogenesis and acute liver damage induced by DENA and $CCl_4$ in Rats.

The Effect of the Bujeonghangam-tang Extract on Hepatocellular Carcinogenesis and Hepatic Cirrhosis Induced by Diethylnitrosarnine and CCl4 in Rats (부정항암탕(扶正抗癌湯) 추출액이 Diethylnitrosamine과 CCl4로 유발된 흰쥐의 간암 형성 및 간경화에 미치는 영향)

  • Moon, Young-Ho;Won, Jin-Hee;Moon, Goo;Heo, Rae-Kyong;Seung, Kee-Moon;Lee, In-Young;Jang, Myung-Joon;Kwon, So-Yeon;Yu, Deok-Seon
    • Journal of Pharmacopuncture
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    • v.13 no.2
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    • pp.13-31
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    • 2010
  • Objective : Bujeonghangam-tang(BH) has been used for cure of tumor as a traditional medicine. This study was carried out to clarify the effect of BH extract on hepatocellular carcinogenesis and hepatic cirrhosis induced by Diethylnitrosamine(DENA) and $CCl_4$ in Rats. Method : Experimental groups were divided into two, 8th and 12th week groups, and subdivided into four; normal group(Nor), cirrhosis and hepatic cancer inducing control group(Con), and BH extract 320 mg/kg/day(BHA) or 640 mg/kg/day(BHB) administered groups to Con. Results: In the 8th week group: The body weight decreased significantly in Con compared with the Nor. The activities of transaminase, alkaline phosphatase(ALP), and lactacte dehydrogenase(LDH) were significantly increased(p<0.05) in the Con compared with Nor, but decreased in the BHA and BHB compared with Con. Alpha fetoprotein(AFP) were the most increased in the Con compared to BHA and BHB. The results of light microscopical observation, a number of hepatocytes were damaged in the Con compared with Nor and BH extract administerd groups. The number of hepatic p53 positive cells was reduced in the BH extract administered groups. According to the electron microscopical observation, hepatocarcinoma cells were observed distinctly in the Con compared with BH extract administered groups. In the 12 weeks group: The results of body were similar to 8th week groups. The activities of transaminase and ALT were significantly increased(p<0.05) in the Con compared with Nor. LDH was significantly(p<0.05) increased in the Con compared with Nor but significantly (p<0.05) decreased in the BHB. Alpha fetoprotein(AFP) were the most increased in the Con among ex perimental groups. The activities of superoxide dismutase(SOD) were significantly (p<0.05) increased in the Con, but the activities of catalase were not increased(p<0.05) compared with Nor. The number of hepatic p53 positive cells was increased in the Con. The results of electron microscopical observation were similar to 8th week groups. Conclusion : These results suggest that ad ministration of BH extract suppress or retard DENA and $CCl_4$-induced hepatocellular carcinogenesis and hepatic cirrhosis in rats.

The Effect of Injinho-tang Extract on Hepatocellular Carcinogenesis and Hepatic Cirrhosis Induced by Diethylnitrosamine and CCl4 in Rats (인진호탕(茵蔯蒿湯) 추출액이 Diethylnitrosamine과 CCl4로 유발된 흰쥐의 간암(肝癌) 형성과 간경변(肝硬變)에 미치는 영향)

  • Lee, Jong-Bum;Heo, Rae-Kyong;Seung, Kee-Moon;Moon, Goo;Lee, Jong-Deok;Won, Jin-Hee
    • Journal of Pharmacopuncture
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    • v.12 no.3
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    • pp.5-24
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    • 2009
  • Injinho-tang(IJ) has been used for the treatment of hepatobiliary diseases. This study was performed to observe the effect of IJ extract on the hepatocellular carcinogenesis and hepatic cirrhosis induced by Diethylnitrosamine(DENA) and $CCl_4$ in Rats. Experimental groups were divided into two ; 8th and 12th week group, and subdivided into four; normal group(Nor), hepatocellular cancer and hepatic cirrhosis inducing control group(Con), and IJ extract 260mg/kg/day(IJA) or 520mg/kg/day(IJB) administered groups to Con. The results obtained are as follows: The body weight was decreased in the Con, IJA and IJB compared with the Nor from the 2nd week to the 12th week. The weight of liver and the weight of liver/100g body weight were decreased significantly in Con, IJA and IJB compared with the Nor. The activities of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) were significantly increased in the Con compared with Nor, but decreased in the IJA and IJB compared with Con from the 8th week group. The activities of alkaline phosphatase(ALP), lactacte dehydrogenase (LDH) and alpha fetoprotein(AFP) were increased significantly in the Con compared with Nor, but decreased in the IJA and IJB compared with Con. The activities of superoxide dismutase(SOD) were decreased in the IJA and IJB compared with Con, but the activities of catalase were increased in the IJA and IJB compared with Con. According to the light and electron microscopical observation, IJA and IJB improved the morphological and histopathological changes of the liver injured by DENA and $CCl_4$. The number of hepatic p53 positive cells was decreased in the IJA and IJB compared with Con. These results suggest that administration of IJ extract suppress or retard DENA and $CCl_4$-induced hepatocelluar carcinogenesis and hepatic cirrhosis in rats.

Dehydroepiandrosterone supplement increases malate dehydrogenase activity and decreases NADPH-dependent antioxidant enzyme activity in rat hepatocellular carcinogenesis

  • Kim, Jee-Won;Kim, Sook-Hee;Choi, Hay-Mie
    • Nutrition Research and Practice
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    • v.2 no.2
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    • pp.80-84
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    • 2008
  • 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 ${\sim}5$ fold and glucose 6-phosphate dehydrogenase activities were decreased by ${\sim}25%$ compared to carcinogen treated group. Activities of Se-glutathione peroxidase in the cytotol was decreased siguificantly 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 fimction 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.

Expression of Intracellular Single Chain Antibody Specific to Hepatitis B Virus X Protein (B형 간염 바이러스의 X단백질에 대한 특이항체의 세포 내 발현)

  • Jin, Young Hee;Kim, Hyung-il;Park, Sun
    • IMMUNE NETWORK
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    • v.3 no.1
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    • pp.23-28
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    • 2003
  • Background: Intracellular antibody specific to hepatitis B virus X protein (HBx) might be useful for studying the role of HBx in hepatocellular carcinogenesis and HBV replication. Methods: With variable region genes for H7 monoclonal anti-HBx Ab, we constructed a vector for bacterial expression of single chain Ab (scFv) and a vector for eukaryotic cell expression of it. The expression of H7 scFv and its binding activity against HBx was examined by immunoblotting and immunofluorescence microscopy. Results: H7 scFv expressed in bacterial cells retained reactivity to HBx. We demonstrated its intracytoplasmic expression in CosM6 eukaryotic cells. Conclusion: This is the first study showing the expression of intracellular anti-HBx Ab in eukaryotic cells. H7 scFv may be a good tool to study the function of HBx in HBV infection.

Alteration of X-linked Inhibitors of Apoptosis (XIAP) Expression in Rat Model with DEN-induced Hepatocellular Carcinogenesis

  • Chang, Jae-Jin;Jeon, Su-Yeon;Song, Ji-Ye;Kim, Jin-Hee;Li, Lan;Park, Dae-Hun;Lee, Yun-Lyul;Park, Jeong-Joo;Woo, Dong-Wook;Kim, Gi-Jin;Lee, Min-Jae
    • Molecular & Cellular Toxicology
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    • v.4 no.4
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    • pp.278-284
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    • 2008
  • The X-linked inhibitor of apoptosis (XIAP) is a member of a novel family of inhibitors of apoptosis and has several BIR domains (BIR1, BIR2, and BIR3) and a carboxy-terminal RING zinc-finger. Since suppressionof apoptosis is fundamentally important for carcinogenesis and tumor growth, we investigated the expression and function of XIAP in DEN-induced carcinogenesis using rat model. Wistar rats were injected intraperitoneally with DEN at a dose of 50 mg/kg in twice a week for 12 weeks (Group II) and 16 weeks (Group III) followed by the recovery periods, respectively. The evaluation of DEN-induced carcinogenesis carried out the blood, RT-PCR, histopathological and western blot analysis. The level of blood chemistry including GOT/GPT, albumin, and total bilirubin were significantly exchanged comparing to control and Group I/Group II. The expression of albumin and collagen mRNA were significantly exchanged (P<0.05) in both groups. In addition, AFP mRNA expression decreased more after recovery periods than Group II. XIAP was expressed constitutively in normal rat liver as well as DEN-induced Groups I and Group II. In addition, XIAP expression increased more in Group I with 4 weeks recovery periods than Group I. However, XIAP expression shown to increase in Group lI, otherwise, it was decreased in Group II with 10 weeks repair periods. Taken together, these results suggest the alteration of XIAP expression could be involved in hepatocellular carcinogenesis.

Effects of Dietary Levels of Corn and Tuna Oils on the Formation of Preneoplastic Lesions in Rat Hepatocellular Carcinogenesis (쥐간세포암화과정에서 옥수수기름과 참치기름의 수준에 따른 전암성 병변의 변화)

  • Kim Sook hee;Kang Sang kyoung;Choi Hay mie
    • Journal of Nutrition and Health
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    • v.38 no.1
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    • pp.20-29
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    • 2005
  • This study is conducted to determine the effects of dietary levels of corn and tuna oils on the formation of preneoplastic lesions in die-thylnitrosamine (DEN) induced rat hepatocarcinogenesis. Weanling male Sprague-Dawley rats were fed 2.5, 5, 15, 25% (w/w) corn or tuna oils. Hepatocellular carcinogenesis was induced by DEN (200 mg/kg body weight) and two-thirds partial hepactectomy was carried out 3 weeks later and were sacrificed 8 weeks after DEN initiation. Tuna oil group showed smaller area of placental glutathione S-transferase (GST-P) positive foci than com oil group. Com oil group of 25% (w/w) showed the widest area of GST -P positive foci, and tuna oil group showed significantly smaller area of GST-P positive foci than com oil in 25% (w/w) level but had no differences between oil levels. Thio-barbituric acid reactive substances (TBARS) content was the highest in 25% (w/w) level of tuna oil group fed long chain and highly polyunsaturated fatty acids. Also serum ${\gamma}$ -glutamyltranspeptidase (GGT) activities in 25% level of tuna oil group were significantly higher than by other levels. As oil contents increased, glucose 6-phosphatase (G6Pase) seems to decrease in com oil groups but remained the same in tuna oil groups. Glutathione reductase (GR) activities were significantly higher in tuna oil group, and the higher the level of tuna oil, the higher GR activities. But Cu/Zn superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities didn't seem to be influenced by levels and kind of dietary fats. Therefore, as oil levels increased, com oil rich in n-6 fatty acids promoted carcinogenesis but tuna oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) of n-3 fatty acids suppressed. Although lipid peroxidation products were elevated in 25% (w/w) tuna oil group, GST-P positive foci didn't increase. Therefore pre-neoplastic lesions might be reduced through mediation of a lipid peroxidation process in tuna oil. As fat contents of tuna oil increased, elevated GR activities may give a rise to produce more reduced glutathione in order to protect against free radical attack, and high G6Pase activities remained the same and they contributed to membrane stability. So tuna oil diet seems to protect hepatocarcinogenesis.