• 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.

• Environmental Analysis Health and Toxicology
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• v.8 no.1_2
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• pp.37-58
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• 1993

In order to investigate the toxicities of S-bioallethrin (5-biol) and its combination treatment with N-octyl bicycloheptene dicarboximide (MGK-264), the acute and subacute toxicity, and enzyme activity test were performed. $LD_{50}$ levels of S-biol and MGK-264 in rats are 640 mg/kg and 3, 280 mg/kg respectively. However, when rats were treated with the mixture of S-biol and MGK-264 (1 : 5 ratio), the $LD_{50}$ was decreased to 545 mg/kg. In serological analysis, ALT and LDH were increased in animals treated with the mixture. Also glucose level was significantly increased after 5 weeks in animals treated with both S-biol and the mixture. Other biochemical parameters such as cytochrome P-450 and NADPH-cytochrome c reductase in the liver and kidney were shown to be not significantly changed. Levels of total ATPase and $mg^{2+}$ ATPase were significantly decreased in the liver of animals treated with the mixture after 4-5 weeks. In addition, S-biol can alone decrease total ATPase activity. Total ATPase activity was also significantly decreased in the kidney after 5 week treatment with the mixture. Similarily, glucose-6-phosphatase activity was significantly decreased in animals treated with the mixture. When either S-biol or MGK-264 was administered, cholinesterase and carboxyesterase activities were slightly decreased but they were significantly decreased when the mixture was administered.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.231-231
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• 1996

Paraquat(1.1'-dimethyl-4,4'-bipyridinium ion, PQ)는 전세계적으로 가장 많이 사용되고 있는 농약으로 자살 또는 실수로 마시는 경우 예외없이 폐독성으로 사망하게 된다. 하지만 아직까지 임상에 사용되어지고 있는 효과적인 독성 경감제는 전무한 실정이다. 현재까지 밝혀진 paraquat의 주된 독성기전은 NADPH Cytochrome P$_{450}$ reductase에 의해 산화,환원 반응을 거치는 동안 free radical을 생성하여 세포막에 지질과산화를 일으켜서 세포막의 기능상실과 cell death를 일으킨다고 보고되고 있다. 따라서 본 연구에서는 항산화작용이 뛰어난 아미노산인 taurine(TA)의 radical scarvenging 효과에 의한 PQ 독성경감효과를 in vivo에서 검색하였고, in vitro에서 TA의 PQ 독성경감 mechanism을 밝히고자 하였다. in vivo에서 PQ의 간독성(s-GOT,s-GPT), 신장독성(BUN, Creatinine), 폐 및 전신독성(ALP, MDA, G-6-phosphatase)의 정도를 혈액 및 조직균질액 중에서 검색함으로써 TA의 독성억제효과를 측정하였다.

• Environmental Analysis Health and Toxicology
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• v.15 no.1_2
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• pp.7-12
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• 2000

Scavenging effects on paraquat induced toxicity were investigated by using methanol (MeOH) and ethylacetate (EtoAC) extracts of Lonicera japonica. The results are summerized as follows: 1. To Fe(III)-ADP-NADPH induced microsomal lipid peroixdation, MeOH and EtoAC extracts showed antioxidative activiies and inhibition ratio at 100 $\mu\textrm{g}$/$m\ell$ 44.4% and 73.8% respectively 2. To microsomal NADPH dependent cytochrome p -450 reductase in rat liver, MeOH and EtoAC extracts inhibited the enzyme activiies and inhibition ratio were 26.3% and 44.8% respectively. 3. Administration (30 mg/kg, iv) of paraquat to rats caused the marked elevation of GOT, GPT, LDH, ALP in the serum and lipid peroxides in the microsome as compared to the control group. Serum GTP, LDH, ALP and liver microsomal LPO were reduced significantaly by administration of MeOH extract. (1,000 mg/kg), EtoAC extract (40 mg/kg) and Silymarin (150 mg/kg) as compared to the paraquat group. From the results, MeOH and EtoAc exuacts. of Lonicera japonica showed the useful scavenger and reducer on the paraquat induced hepatotoxicty.

• Preventive Nutrition and Food Science
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• v.13 no.4
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• pp.366-369
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• 2008

Proteins secreted from bifidobacteria are believed to play important roles in human intestines via interacting with different host cells. In this respect, proteins secreted from Bifidobacterium pseudocatanulatum BP1, which has been rarely studied, were analyzed by two-dimensional gel electrophoresis (2DE). Using this approach, approx-imately 21 protein spots on a 2DE gel were detected and 10 of these spots were identified by mass spectrometry. Five spots were identified as hypothetical proteins and the remaining 5 spots were identified as a putative iron-side-rophore binding lipoprotein, a short-chain dehydrogenase/reductase SDR, an exonuclease, cytochrome P450 hydroxylase, and a putative dehydrogenase. The identification of secreted putative iron-siderophore binding lipoprotein was highly interesting since it is an important protein that is involved in ferric iron uptake in pathogenic bacteria. This finding could accelerate studies on the probiotic effect of Bifidobacterium by explaining the competition between bifidobacteria and intestinal pathogens for ferric iron.

• Korean Journal of Pharmacognosy
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• v.36 no.2 s.141
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• pp.81-87
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• 2005

The effects of the DWP-04 [DDB:selenium yeast:glutathione (31.1 : 6.8 : 62.1 (w/w%)] on acetaminophen detoxification enzyme system were studied in rats. Treatment with DWP-04 was prevented againt acetaminophen-induiced hepatotoxicity in rat as evidenced by the decreased formation of lipid peroxide. Effect of DWP-04 on the activities of free radical-generating enzymes, free radical scavenging enzymes and glutathione-related enzymes as well as detoxification mechanism of DWP-04 against acetaminophen-treated was investigated in rat. Activities of cytochrome p450, cytochrome b5, aminopyrine demethylase and aniline hydroxylase as free radical-generating enzymes activities were decreased by the treatment with DWP-04 against acetaminophen treated. Although acetaminophen-induced hepatotoxicity results in the significantly decrease in the level of hepatic glutathione and activities of glutathine S-transferase, quinone reductase, glutathione reductase and ${\gamma}-glutamyl-$cysteine synthetase, these decreasing effects were markedly lowered in the DWP-04-treated rat. Therefore, it was concluded that the mechanism for the observed preventive effect of DWP-04 against the acetaminophen-induced hepatotoxicity was associated with the decreased activities in the free radical-generating enzyme system.

• Journal of Life Science
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• v.18 no.3
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• pp.381-386
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• 2008

Deep sea water was tested for cancer chemopreventive activity by measuring the activities of ${\beta}-$ naphthoflavone $({\beta}-NF)-induced$ cytochrome P 450 1A2 (CYP 1A2), quinone reductase (QR) and glutathione-S-transferase (GST), glutathione (GSH) levels, and ornithine decarboxylase (ODC) activity. The in vitro incubation of rat liver microsome with deep sea water (a hardness range of $100{\sim}1,000$) showed a hardness-dependent inhibition of CYP 1A2 activity. QR and GST activities were induced about $1.1{\sim}1.2$ fold with the treatment of deep sea water in murine hepatoma Hepa 1clc7 cells. In addition GSH levels were increased $1.3{\sim}1.4$ fold in a hardness range of $100{\sim}1,000$. The deep sea water showed 20.3 and 35.0% inhibition of 12-O- tetradecanoylphorbol-13-a-cetate (TPA)-induced ODC activity at hardness 800 and 1,000, respectively. Therefore, deep sea water is worth further investigation with respect to cancer chemoprevention or therapy.

• Journal of Sasang Constitutional Medicine
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• v.17 no.1
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• pp.130-141
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• 2005

1. Objectives The present study was carried out to investigate the effects of Chungpyesagan-tang on the $CCI_4-induced$ Liver Damage in Rats. 2. Methods Sprague-Dawley rats were devided into 5 experimental groups : Normal, $NS+CCI_4(Solid$ extract of $CCI_4$ injection group after Normal Saline feed), $CP+CCI_4(Solid$ extract of $CCI_4$ injection group after Chungpyesagantang feed), $CCI_4+NS(Nomal$ Saline feed group after $CCI_4$ injection), $CCI_4+CP(Solid$ extract of Chungpyesagantang feed group after $CCI_4$ injection). Biochemical assays for serum enzyme activities such as AST, ALT, ALP, BUN, Creatinine, Uric Acid, Total Protein, Albumin, Total Cholesterol, Triglyceride, Glucose, and mRNA Revelation of Cytochrome p450 and activities such as LPO(Lipid Peroxidation), GSH(Glutathione), GST(Glutathione-S- Transferase), Glutathione Reductase, Glutathione Peroxidase, SOD(Superoxide Dismutase), Catalase, Hydroxyproline, and ${\beta}-Glucuronidase$ were performed. 3. Results 1) $CP+CCI_4$ showed significantly lower relation of Cytochrome p450 than $NS+CCI_4$. 2) As to LPO Hydroxyproline, $CCI_4+CP$ showed significantly lower activity than $CCI_4+NS$. 3) As to GSH GST Glutathione Peroxidase Catalase, $CP+CCI_4$ showed higher activity than $NS+CCI_4$, $CCI_4+CP$ showed significantly higher activity than $CCI_4+NS$. 4) As to Glutathione Reductase SOD, $CCI_4+CP$ showed significantly higher activity than $CCI_4+NS$. 5) As to ${\beta}-Glucuronidase$, $CP+CCI_4$ showed signficantly lower activity than $NS+CCI_4$. 4. Conclusions Chungpyesagantang has the recovering effects on the $CCI_4-induced$ Liver Damage.

• Toxicological Research
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• v.4 no.1
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• pp.13-22
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• 1988

The inhibitory effect of three polyacetylene compounds, panaxydol, panaxynol and panaxytriol isolated from Panax ginseng C.A. Meyer on $CCl_4$induced lipid peroxidation in vivo and in vitro hepatic microsomal lipid peroxidation induced by ADP-$Fe^{3+}$, NADPH and NADPH-cytochrome P-450 reductase were investigated. Their effects on lowering the lipid peroxide levels both in serum and liver and lowering the serum enzyme (GOT, GPT, LDH) activities without the $CCl_4$-induction were also determined. Male ICR mice were pretreated i.p. with polyacetylene compounds or DL-${\alpha}$-tocopherol before administration of $CCl_4$ i.p. and 20 hr after the administration of $CCl_4,$ serum and liver were analyzed. Hepatic microsome was isolated and used for the in vitro NADPH-dependent lipid peroxidation system. Except for panaxynol, treatment with polyacetylenes to control mice did not reduce the levels of lipid peroxides and serum enzyme activities. Panaxynol itself inhibited lipid peroxidation in the liver of normal mice. Polyacetylene compounds protected from the $CCl_4$-induced hepatic lipid peroxidation and lowered serum lipid peroxide levels. Polyacetylenes also inhibited the in virto hepatic microsomal lipid peroxidation in a dose-dependent manner. The results suggest that panaxydol, panaxynol and panaxytriol seem to be the antioxidant components which contribute the anti-aging activities of Panax ginseng C.A. Meyer.

• Natural Product Sciences
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• v.10 no.4
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• pp.182-189
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• 2004

To find the action mechanism of the MeOH extract (LFS) of Ligularia fischeri var. spiciformis herbs (Compositae) and its active component, 3,4-dicaffeoylquinic acid (DCQA) on antihepatotoxicity, the effect was investigated on hepatic lipid perxodation and drug-metabolizing enzyme activities in acetaminophen-treated rat. Pretreatment with 250 mg/kg LFS (p.o.) and 10 mg/kg DCQA (p.o.) significantly decreased hepatic lipid peroxidation caused by acetaminophen injection. Further, LFS and DCQA inhibited hepatic microsomal enzyme activation such as hepatic P-450 cytochrome $b_5$, aniline hydroxylase and aminopyrine N-demethylase, suggesting that the two substances might effectively prevent the metabolic activation or scavenge electrophilic intermediates capable of causing hepatotoxicity. Both LFS and DCQA increased hepatic glutathione content and glutathione reductase activity, indicating that both resultantly prevented hepatotoxicity via antioxidative mechanism. Therefore, it was found that LFS had antihepatotoxicity based on the antioxidative action of DCQA.