• Food Science and Biotechnology
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• 제15권2호
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• pp.238-243
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• 2006

The methanol extract of waxy brown rice fermented with Agrocybe cylindracea was prepared. The extract was then freeze dried and fed to rats at the level of 0.5, 1.0, 2.0 g/kg body weight for 14 days, followed by the treatment with carbon tetrachloride for three consecutive days to induce hepatotoxicity. After sacrificing the rats, the enzyme activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and ${\gamma}$-glutamyl transpeptidase (${\gamma}$-GTP) in serum was determined. Biochemical analysis on serum for albumin, total protein, triglyceride, and total as well as HDL-cholesterol were carried out along with a histopathological study of liver tissues. Based on these data, we suggest that the waxy brown rice cultured with A. cylindracea may exert hepatoprotective activity against hepatotoxicity caused by chemicals such as carbon tetrachloride.

• 약학회지
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• 제40권6호
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• pp.727-733
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• 1996

2-(Allylthio)pyrazine is effective in selectively suppressing constitutive and inducible expression of cytochrome P450 2E1. The effect of 2-(allylthio)pyrazine against potentiat ed chemical injury was studied in rats. Vitamin-A pretreatment of rats substantially increased carbon tetrachloride hepatotoxicity, as supported by an ~4-fold increase in serum alanine aminotransferase (ALT) activity. Concomitant pretreatment of rats with 2-(allylthio)pyrazine at the daily dose of 200mg/kg resulted in a 76% decrease in vitamin-A-potentiated hepatotoxicity, which supported the possibility that 2-(allylthio)pyrazine protects the liver against chemical-induced hepatic injury by the mechanism associated with Kupffer cell inactivation. Pyridine pretreatment caused substantial enhancement in carbon tetrachloride hepatotoxicity. 2-(Allylthio)pyrazine treatment of rats reduced the pyridine-potentiated toxicity in a dose-dependent manner. Animals treated with both pyridine and 2-(allylthio)pyrazine prior to intoxicating dose of CCl$_4$ resulted in 85% and 47% decreases in pyridine-increased triglycerides and cholesterol levels in the liver. The protective effect of 2-(allylthio)pyrazine on the DNA strand breakage induced by benzenetriol was assessed by measuring the conversion of supercoiled ${\Phi}x$-174 DNA to the open relaxed form. 2-(Allylthio)pyrazine blocked the benzenetriol-induced conversion of supercoiled DNA to open circular form in a dose-dependent manner. The presence of 2-(allylthio)pyrazine at the doses from I to 10mM in the incubation mixture containing 5 ${\mu}$M benzenetriol completely protected benzenetriol-induced DNA strand breakage with the EC50 for the 2-(allylthio)pyrazine blocking being noted as ~220 ${\mu}$M, whereas allyl disulfide exerted protecting effect at relatively high concentrations (i.e. ~850 ${\mu}$M), suggesting that 2-(allylthio)pyrazine effectively scavenges the reactive oxygen species. These results provide evidence that 2-(allylthio)pyrazine blocks vitamin A- or pyridine-potentiated CCl$_4$ hepatotoxicity and that the agent is active in protecting DNA by scavenging the reactive oxygen species.

• Nutrition Research and Practice
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• 제4권2호
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• pp.93-98
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• 2010

Our previous study demonstrated that methanolic extract of Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae) has the potential to induce detoxifying enzymes such as NAD(P)H:(quinone acceptor) oxidoreductase 1 (EC 1.6.99.2) (NQO1, QR) and glutathione S-transferase (GST). In this study we further fractionated methanolic extract of Chrysanthemum zawadskii and investigated the detoxifying enzyme-inducing potential of each fraction. The fraction (CZ-6) shown the highest QR-inducing activity was found to contain (+)-(3S,4S,5R,8S)-(E)-8-acetoxy-4-hydroxy-3-isovaleroyloxy-2-(hexa-2,4-diynyliden)-1,6-dioxaspiro [4,5] decane and increased QR enzyme activity in a dose-dependent manner. Furthermore, CZ-6 fraction caused a dose-dependent enhancement of luciferase activity in HepG2-C8 cells generated by stably transfecting antioxidant response element-luciferase gene construct, suggesting that it induces antioxidant/detoxifying enzymes through antioxidant response element (ARE)-mediated transcriptional activation of the relevant genes. Although CZ-6 fraction failed to induce hepatic QR in mice over the control, it restored QR activity suppressed by $CCl_4$ treatment to the control level. Hepatic injury induced by $CCl_4$ was also slightly protected by pretreatment with CZ-6. In conclusion, although CZ-6 fractionated from methanolic extract of Chrysanthemum zawadskii did not cause a significant QR induction in mice organs such as liver, kidney, and stomach, it showed protective effect from liver damage caused by $CCl_4$.

• 한국임상수의학회지
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• 제24권3호
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• pp.384-391
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• 2007

This study was conducted to clarify the effects of the Korean raisin (Hovenia dulcis Thunb) extracts and polyherbal extracts consisted of 6 types herbal extracts including HDT (HDTmix) on $CCl_4$ induced organ damages. Extracts were prepared by autoclave ($121^{\circ}C$, 15 psi, 3 hours) and filtered with nylon cloth and filter paper then freezing dried. Male Sprague-Dawley rats $(200^{\circ}{\ae}20g)$ were used as experimental groups, which were divided into 5 groups; intact control group (100 mg/kg), $CCl_4$ dosing group (100 mg/kg), $CCl_4$ dosing after HDT extract dosing group (100 mg/kg), $CCl_4$ dosing after HDTmix dosing group (100 mg/kg), Silymarin dosing group (5 mg/kg) after all test articles were orally dosed once a day for 28 days. They were sacrifiled under ether anesthesia. HDT extracts and HDTmix dramatically inhibits the $CCl_4$ intoxicated hepato/nephropathies with immuno-suppress changes on the spleen. They showed more dramatical protective effects on most of specific organs compared to that of Silymarin 5 mg/kg except for hepatoprotective effects in which, quite similar effects were detected. In addition, HDT extracts showed synergic effects with other types of herbal extracts because HDTmix showed more favorable protective effects on the all specific organs showing $CCl_4-related$ histopathological changes compared to HDT extracts.

• 대한약리학회지
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• 제32권3호
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• pp.407-416
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• 1996

간독성물질인 $CCl_4$의 대사에서 반응성이 높은 대사중간체의 증가가 P450 2E1의 활성 및 발현증가와 관련된다. YH439는 랫트에서 사염화탄소에 의하여 유발된 간 손상에 보호효과가 탁월하였고, 각종 독성물질에 의하여 발생하는 간염을 억제하며 P450 2E1의 발현을 억제하는 것으로 나타났다. P450 2E1의 발현억제가 YH439의 간장보호작용의 일부기전으로 해석되나 free radical 공격의 제어, 방어과정에 관련된 탐식세포의 역할등 간장독성에 관련된 YH439의 영향 및 관련된 기초연구는 완전히 확립되어 있지 않다. 본 연구에서는 상승적인 화학적 독성에 대한 YH439의 보호효과를 관찰하였다. Retinoyl palmiate (Vit-A)를 전처러하고 YH439를 처리한 rat의 경우 $CCl_4$ 단독투여군에 비하여 혈장 alanine aminotransferase (ALT)활성이 5배로 증가하여 $CCl_4$에 의한 간독성을 현저히 강화시켰으나, YH439와 Vit-A를 동시에 전처리한 rats에 있어서는 Vit-A에 의하여 강화된 독성이 94% 감소하였다. Vit-A에 의한 혈장 ALT 활성 증가는 Kupffer cell 활성을 선택적으로 억제하는 $GdCl_3$의 투여에 의해 완전히 차단되어 YH439가 Kupffer cell 활성억제를 매개로 상승적 간손상에 대하여 보호효과가 있음을 지지한다. Propyl sulfide의 전처치는 $CCl_4$에 의해 유도되는 간독성을 $CCl_4$ 단독투여와 비교했을때 5배 이상 증가시켰으나, Propyl sulfide와 YH439를 병용투여할 경우 propyl sulfide에 의해 강화되는 간독성이 YH439의 투여용량에 의존적으로 감소하였고, propyl sufide와 $CCl_4$에 의한 지질과산화의 증가가 YH439에 의하여 용량의존적으로 억제되는 것으로 나타났다. Propyl sulfide에 의하여 강화된 간독성의 차단은 YH439가 P450 2E1 발현조절을 통하여 간독성을 제어함을 지지한다. 그러나 YH439는 pyridine과 $CCl_4$에 의한 독성을 억제시키지 못하였다. 이는 Pyridine에 의해 유도되는 다른 형의 P450발현이 YH439에 의해 억제되지 못하는 이유로 해석된다. 중금속에 의해 유도되는 간독성에 대한 YH439의 보호효과를 ICR mice에서 관찰하였을 때 $CdCl_2$를 1회 투여할때 ALT와 aspartate aminotransferase (AST)활성이 $5{\sim}6$배 증가하였으나 YH439를 투여한 후 $CdC1_2$를 투여한 동물에 있어서는 투여후 6시간에 AST의 증가가 유의성 있게 억제되었다. 그러나 YH439는 thioacetamide에 의하여 유발된 liver fibrosis에는 개선효과가 없는 것으로 나타났다. 이러한 결과는 YH439가 Kupffer cell 불활성화를 통하여 Vit-A에 의해 유도되는 간독성을 효과적으로 방어하고, YH439에 의한 P450 2E1의 발현억제는 propyl sulfide를 경유하는 간독성 차단과 관계되며, YH439는 중금속으로 유도된 조직독성에 방어효과가 있음을 지지한다.

• 대한약리학회지
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• 제32권1호
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• pp.75-82
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• 1996

사염화 탄소에 의한 과산화 지질 증가 및 간 손상에 calcium 및 Kupffer cell의 역할 및 calcium channel blocker의 간 손상에 대한 방어 효과를 연구하였다. 사염화 탄소는 (1 gm/kg, ig) 간의 malondialdehyde (nmole/gm liver) 및 혈중 AST와 ALT (lU/ml) 활성도의 현저한 증가를 나타내었다. 고 농도의 Retinol (250,000U/kg/day)로 인한 Kupffer cell의 활성 증가는 사염화 탄소에 의한 간 과산화 지질 증가 및 간 손상에 상승 작용을 나타낸 반면, $GdCl_3$ 전처리는 $CCl_4$로 인한 ALT의 증가를 감소시켰다. 한편 Retinol 처치군에 Diltiazem (10mg/kg/day)을 병행하여 처치한 결과, 사염화 탄소에 의한 혈중 AST 및 ALT의 증가를 Retinol 단독 처치군에 비하여 현저하게 억제시킬 수 있었다. 이 결과들이 Retinol 혹은 Diltiazem의 투여에 의한 사염화 탄소가 cytochrome P450에 의한 대사 활성 또는 GSH와 관련된 항산화 기전에 미치는 영향에 기인한 것인가를 규명하기 위하여 cytochrome P450, cytochrome P4502El 활성도, GSH reductase 및 GSH peroxidase 활성도를 측정하였다. 그 결과, Retinol 및 Diltiazem의 전처리는 이들 효소의 활성도에 미치는 영향은 대조군에 비하여 유의한 차이가 없었다. 이상의 실험 결과를 종합하여 보면, 사염화 탄소의 투여에 의한 간 손상은 세포내 calcium의 증가를 가져오며, 이는 이차적으로 Kupffer cell을 활성화 시켜 이미 손상된 간세포의 독성을 증가시켰으며, calcium channel blocker인 Diltiazem의 투여는 사염화 탄소의 간독성을 현저하게 감소시키는 효과를 나타내었다.

• Biomolecules & Therapeutics
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• 제4권1호
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• pp.89-96
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• 1996

The effect of Cimicifuga heracleifolia on CC1$_4$-induced hepatotoxicity was investigated. Cimicifuga heracleifolia has been used to diaphoresis, antipyretics and detoxification in oriental remedy. We examined the effect of Cimicifuga heracleifolia methanol extract by blood chemical analysis and histopathologic examination. ALT and AST were decreased by 38% and 67% in pretreatment group of Cimicifuga heracleifolia compared to CC1$_4$control group respectively. There were significant changes neither in total protein, albumin, triglyceride and cholesterol nor in BUN and creatinine. In histopathologic examination, there were severe necrosis and hemorrhage with infiltration of inflammatory cells around the central vein, zone 3 in the liver of CC1$_4$ treated rat. Ballooning degeneration of hepatocytes were frequently noted in the periphery of the hemorrhagic necrosis. In Cimicifuga heracleifolia pretreatment group, we observed mild degree of ballooning degeneration and inflammatory cell infiltration. No gross necrosis was observed. We measured malondialdehyde (MDA) formation by TBA method. It showed that the formation of MDA in Cimicifuga heracleifolia pretreatment group was decreased compared to the $CCl_4$control group. We got the result of the effect of Cimicifuga heracleifolia on CC1$_4$-induced hepatotoxicity by decreasing serum ALT and AST. It seems that the decrease of lipid peroxidation is related to the recovery effect.

• 생명과학회지
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• 제15권4호
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• pp.572-577
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• 2005

음양곽의 항산화 효과를 규명하기 위하여 흰쥐(Sprague-Dawley계)를 사용하여 음양곽 추출물을 2주간 복강내로 투여하고 $CCl_4$에 의한 간독성 경감기전을 혈액 및 간 조직에서의 효소 변동과 간 조직을 병리학적으로 관찰하였다. $CCl_4$의 투여로 AST, ALT, MDA가 증가하였으나 음양곽을 전처리하고 $CCl_4$를 후 투여한 경우에는 AST, ALT, MDA가 감소하였다. $CCl_4$의 투여로 SOD, catalase, GPx가 감소하였으나 음양 곽 전처리 한 후 $CCl_4$를 투여 한 경우에는 SOD, catalase, GPx가 증가하였다. 음양곽은 $CCl_4$로 유도된 free radicals를 scavenging함으로써 간독성을 경감시키는 것으로 사료된다. 위의 생리활성과 항산화계 변화 지표에서 나타난 음양곽의 간기능 보호효과를 형태학적으로 확인하기 위한 조직병리학적 검사결과 음양곽이 세포막의 소기관들을 과산화로부터 보호함으로써 효소활성의 최적구조를 유지시켜 간 손상을 완화시키는 것으로 사료된다.

• 한국응용과학기술학회지
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• 제27권3호
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• pp.290-299
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• 2010

The bioactive effects of ethanol extracts from fly maggot (ME) on reduction of plasma lipids levels in rats fed high-fat diets (Expt. Ⅰ), and on liver function recovery of hepatotoxicity rats by intraperitoneal injection of carbon tetrachloride ($CCl_4$) or by orally administration of alcohol (Expt. II) were investigated. In expt. I, twenty seven, male rat SDS(sprague dawley strain) were randomly assigned to three treated groups, including normal control group, HF (group with high fat diets which have no extracts) and HFE (HF plus orally administered doses of ME extract at 5.0 mg/100g of body weight). In expt. II, forty five, male rats (SDS) were randomly assigned to each of the five groups: T1 (control), T2 (intraperitoneal injection of $CCl_4$), T3 (intraperitoneal injection of $CCl_4$ after orally administered with ME), T4 (orally administered with combination of ME and alcohol), T5 (orally administration of ME after orally administered with alcohol). There were significant decreases in plasma (TAG), (TC), (LDL-C) in the HFE group with orally administered doses of ME at 5.0 mg/100g of body weight, respectively, however, the (HDL-C) were significantly increased in HFE group as compared to HF group with high fat diets which have no extracts (p<0.05). The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), ${\gamma}$-glutamyl transferse(${\gamma}$-GTP) and bilirubin were highest in T2 or T3, and high in order T4 or T5, and lowest in T1 except for bilirubin which has same with T4, T5 (p<0.05). The high recovery of liver damage by $CCl_4$ from the light microscopic appearance was observed in rats (T3) with extracts, and also high in T4 than T5 by orally administrated with alcohol. In conclusion, the ethanol extracts from fly maggot may have a bioactive effects to prevent for human lipids disorder and alcoholic disease.

• 한국식품과학회지
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• 제41권1호
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• pp.93-99
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• 2009

꾸지뽕 당단백질이 간의 조직에 존재하는 항산화계 해독효소의 활성을 증가시켜서 $CCl_4$로 유도된 간독성화 과정에서 생성된 ROS에 의해 야기되는 산화적 스트레스를 억제하는 scavenger로서 기능을 가지고 있는 것으로 분석된다. 또한 혈청 중 LDH 활성증가는 간 및 기타조직의 질환 및 악성 종양 등에서 나타나는 소견으로 LDH를 내포한 조직이 파괴될 때 혈액으로 흘러나와 혈중 LDH가 상승하며, 혈액 중 지질과산화 반응은 생체조직막의 다가불포화지방산 유리기에 의해 산화적 분해를 일으키는 지표로 사용되는 TBARS의 수치, DNA 염기의 deamination 등을 유도함으로써, 유전자의 돌연변이(mutagenesis)로 인한 세포독성을 일으키는 NO 등의 수치가 유의적인 수준으로 억제될 뿐만 아니라, 염증 매개시 단백질인 NF-kB(p50)을 억제함으로써 $CCl_4$에 의한 간독성 과정에서 촉진된 염증 신호전달기전을 억제할 수 있었다. 따라서 꾸지뽕 당단백질은 탁월한 천연 항산화제로서 간의 독성 및 염증 반응을 억제하는 것으로 실험결과 분석된다.