• Biomolecules & Therapeutics
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• 제26권2호
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• pp.218-223
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• 2018

The liver is an essential organ for the detoxification of exogenous xenobiotics, drugs and toxic substances. The incidence rate of non-alcoholic liver injury increases due to dietary habit change and drug use increase. Our previous study demonstrated that Ecklonia stolonifera (ES) formulation has hepatoprotective effect against alcohol-induced liver injury in rat and tacrine-induced hepatotoxicity in HepG2 cells. This present study was designated to elucidate hepatoprotective effects of ES formulation against carbon tetrachloride ($CCl_4$)-induced liver injury in Sprague Dawley rat. Sixty rats were randomly divided into six groups. The rats were treated orally with ES formulation and silymarin (served as positive control, only 100 mg/kg/day) at a dose of 50, 100, or 200 mg/kg/day for 21 days. Seven days after treatment, liver injury was induced by intraperitoneal injection of $CCl_4$ (1.5 ml/kg, twice a week for 14 days). The administration of $CCl_4$ exhibited significant elevation of hepatic enzymes (like AST and ALT), and decrease of antioxidant related enzymes (superoxide dismutase, glutathione peroxidase and catalase) and glutathione. Then, it leaded to DNA damages (8-oxo-2'-deoxyguanosine) and lipid peroxidation (malondialdehyde). Administration of ES formulation inhibited imbalance of above factors compared to $CCl_4$ induced rat in a dose dependent manner. Real time PCR analysis indicates that CYP2E1 was upregulated in $CCl_4$ induced rat. However, increased gene expression was compromised by ES formulation treatment. These findings suggests that ES formulation could protect hepatotoxicity caused by $CCl_4$ via two pathways: elevation of antioxidant enzymes and normalization of CYP2E1 enzyme.

• Natural Product Sciences
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• 제10권4호
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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.

• Environmental Analysis Health and Toxicology
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• 제14권3호
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• pp.87-93
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• 1999

Antioxidative and scavenging effects were investigated by using two hyaroxycinnamic acids (caffeetannins). such as caffeic acid and chlorogenic acid, on oxidative stress and hepatotoxicity that induced by paraquat. The results are summerized as follows: 1. To assess radical scavenging ability, reduction concentration (IC$\sub$50/) of 1.1 diphenyl-2-dipicrylhydrazine (DPPH) were measured. IC$\sub$50/ values of caffeic acid and chlorogenic acid were 29.7 ${\pm}$0.6 ${\mu}$M and 26.0${\pm}$0.5 ${\mu}$M respectively. Their radical scavenging activities showed concentration-dependent manner. 2. In H$_2$O$_2$-induced hemolysis assay to rat blood, caffeic acid and chlorogenic acid led to different effects, whose hemolysis inhibition ratios at 100 ${\mu}$M were 45.2${\pm}$7.1% and 11.6${\pm}$3.1% respectively 3. In hypoxanthine-xanthine oxidase system producing superoxide anion, caffeic acid and chlorogenic acid showed different inhibitory activities of xanthine oxidase showing 36.8${\pm}$4.3% and 5.4${\pm}$2.3% respectively. 4. To microsomal NADPH dependent cytochrome p-450 reductase in rat liver, paraquat consumed NADPH at a dose-dependent manner from 0 to 1 ${\mu}$M paraquat concentration. Caffeic acid and chlorogenic acid blocked NADPH consumption rates at concentration-dependent manner and inhibition ratios at 100 ${\mu}$M were 67.6% and 59.2% respectively. 5. Administration (30mg/kg, iv) of paraquat to rats caused the marked elevation of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and lipid peroxides (LPO) in the serum and lipid peroxides in the microsome as compared to the control group. Serum GOT, GPT, LDH, ALP and LPO and liver microsomal LPO were reduced significantly by caffeic acid (50mg/kg), chlorogenic acid (25mg/kg) and silymarin (150 mg/kg) as compared to the paraquat group. From these results, caffeic acid and chlorogenic acid exerted their antioxidative agents by removing reactive oxygen substance (ROS) and scavenging effects by inhibiting ROS generating enzyme. As a general, two hydroxyeinnamic acids showed the useful compounds for scavenger and reducer on the paraquat induced hepatotoxicity.

• Toxicological Research
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• 제23권4호
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• pp.301-309
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• 2007

Paecilomyces tenuipes (PT), one of the Ascomycetes family, has been used for medicinal purposes due to its broad pharmacological activities. The present study was undertaken to investigate the hepatoprotective effects of PT water extracts against $CCl_4$-induced hepatotoxicity in primary cultures of adult rat hepatocytes. When the extract of PT was directly added into the culture medium at 1, 2, and 5 mg/ml, the extracts not only reduce the $CCl_4$-induced elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase, and lipid peroxide, but also protect cultured hepatocytes from $CCl_4$-induced reduction of reduced glutathione, glutathione reductase, glutathione-S-transferase, glutathione peroxidase, catalase and superoxide dismutase. In addition, the effects of PT water extracts on cytochrome P450 enzymes were relatively marginal, indicating that the hepatoprotective effects of PT extract against $CCl_4$-induced toxicity might not be due to the inhibition of $CCl_4$ activation. In conclusion, the PT extracts were effective in protecting against $CCl_4$ induced hepatotoxicity in hepatocyte cultures, at least in part, by scavenging free radicals, and by modulating enzyme systems involved in cellular oxidative stress.

• 생약학회지
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• 제27권3호
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• pp.159-166
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• 1996

To evaluate hepatoprotective effects of G009, an hepatoprotective agent which was extracted from the mycelia of Ganoderma lucidum IY009, we were, studied using $CCl_4$-and galactosamine-induced hepatotoxicity in rats. The ratio of liver weight to body weight, the value of glutamic oxaloacetic transaminase(GOT) and glutamic pyruvic transaminase (GPT) activities, the change of a lipids in serum, and the inhibitory activity of malondialdehyde (MDA) formation in serum and liver homogenate were determined in rats. G009 was not significantly changed of the ratio of liver weight to body weight and the content of lipids in serum, but reduced the serum GOT and GPT values in $CCl_4$-and galactosamine-induced hepatotoxicity in rat. Especially, protective effect of G009 on rat hepatic injuries induced by galactosamine was significantly appeared. $CCl_4$ increased markedly the formation of lipid peroxides in the liver homogenate, and serum. The increase of lipid peroxides by $CCl_4$-induced hepatotoxicity was markedly reduced by the treatment with G009. These results suggest that the hepatoprotective effects of G009 may be correlated with its anti-lipid peroxidative activity, therefore, it may be potential agent for hepatic disease.

• The Korean Journal of Physiology and Pharmacology
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• 제16권6호
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• pp.469-476
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• 2012

2,3,7,8-Tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) is an environmental toxicant with a polyhalogenated aromatic hydrocarbon structure and is one of the most toxic man-made chemicals. Exposure to 2,3,7,8-TCDD induces reproductive toxicity, immunotoxicity, and hepatotoxicity. In this study, we evaluated how 2,3,7,8-TCDD-induced hepatotoxicity affect the expression of heat shock proteins and antioxidant enzymes using the real-time polymerase chain reaction (PCR) in rat. 2,3,7,8-TCDD increased heat shock protein (Hsp27, ${\alpha}$-B-crystallin, Mortalin, Hsp105, and Hsp90s) and antioxidant enzymes (SOD-3, GST and catalase) expression after a 1 day exposure in livers of rats, whereas heat shock protein (${\alpha}$-B-crystallin, Hsp90, and GRP78) and antioxidant enzymes (SOD-1, SOD-3, catalase, GST, and GPXs) expression decreased on day 2 and then slowly recovered back to control levels on day 8. These results suggest that heat shock proteins and antioxidant enzymes were induced as protective mechanisms against 2,3,7,8-TCDD induced hepatotoxicity, and that prolonged exposure depressed their levels, which recovered to control levels due to reduced 2,3,7,8-TCDD induced hepatotoxicity.

• 한국식품영양과학회지
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• 제31권1호
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• pp.87-91
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• 2002

톳 에탄올 추출물이 알코올을 투여한 흰쥐의 간조직 손상에 미치는 영향을 알아보기 위해 정상군, 알코올 투여군(35% ethanol, 10mL/kg B.W./day) 알코올 및 톳 에탄올 추출물 200mg/kg 및 400mg/kg 병합투여군의 4군으로 나누어 6간 사육 후 체중 증가율, 식이효율, 혈청중 ALT 및 ALP활성, 간조직의 손상억제효과를 검토하기 위해 SOD, catalase, XO 및 GSH-Px효소 활성을 측정하고 지질과산화물인 TBARS 와 GSH함량을 측정한 결과는 다음과 같다. 1) 체중증가율은 알코올 투여군이 정상군에 비하여 약 38%가 감소되었으나 알코올과 톳 에탄올 추출물(kg당 200mg 및 400mg)을 병합투여하여 알코올에 의해 둔화된 체중증가율이 정상군에 근접하도록 회복되었으며, 식이효율은 알코올 투여군이 정상군에 비하여 약 50%가 감소되었으나 톳 에탄올 추출물과 알코올의 병합투여로 증가되었다. 2) 간 손상지표 중의 하나인 혈청 ALT 및 ASP활성의 경우, 알코올 투여로 정상군에 비하여 160%정도 유의적으로 증가되었으나, 알코올과 톳 에탄올 추출물의 병합 투여로 알코올 투여군에 비하여 각각 63% 및 47%가 감소되었다. 3) 톳 에탄올 추출물은 알코올에 의해 증가된 세포질내의 XO활성을 감소시키지 못했으나 SOD, catalase 및 GSH-Px활성은 알코올 투여군에 비하여 각 56%, 38% 및 28%가 감소되었다. 4) 알코올만을 투여한 군의 TBARS함량은 정상군에 비하여 약 129%이상 증가되었으나, 알코올과 톳 에탄올 추출물 병합 투여로 알코올만을 투여한 군에 비하여 각각 34%, 56%의 감소를 나타냈는데 특히 400mg 투여가 더 많은 감소 효과를 보였다. 5) 알코올 투여로 간조직중의 GSH함량은 정상군에 비해 약 38%가 감소되었으나, 알코올과 톳 에탄올 추출물 병합 투여로 알코올 투여군에 비하여 각각 33% 및 66%가 증가되었다. 특히 400 mg 투여군의 경우 GSH함량 상승 효과가 우수하였다.

• 한국자원식물학회지
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• 제28권5호
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• pp.551-560
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• 2015

본 연구는 산겨릅나무 세포배양 추출물이 D-galactosamine에 의해 유발된 간독성에 따른 보호 효과를 살펴보았다. 간 조직 내 국소적 지방 변성과 염증세포 침윤은 산겨릅나무 세포배양 추출물을 처리한 실험군에서 크게 감소되는 경향을 보였다. 또한 산겨릅나무 세포배양 추출물을 처리한 실험군은 간 손상에 의해 급격히 증가된 AST와 ALT, LDH 및 ALP의 활성과 조직 내 지질함량과 과산화지질함량이 감소되는 것으로 나타나 산겨릅나무 세포배양 추출물이 D-galactosamine으로 인한 혈중 효소활성과 조직 내 지질함량을 개선하는 것으로 조사되었다. 이와 더불어 산겨릅나무 세포배양 추출물을 처리한 실험군은 염증반응을 촉진시켜 조직 상해 및 괴사를 유도하는 TNF-α의 발현 수준이 간독성을 유발한 실험군에 비해 낮은 것으로 확인되었고 항산화효소의 활성을 효과적으로 조절하였다. 이러한 결과로 미루어 보아 산겨릅나무 세포배양 추출물은 D-galactosamine에 의한 조직 괴사를 감소시키고 혈중 효소의 활성과 조직 내 지질함량을 개선할 뿐만 아니라 염증 반응 인자의 발현과 항산화효소 활성을 조절하고 있어 간독성에 대한 보호효과가 매우 높은 것으로 사료된다.

• Journal of Ginseng Research
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• 제27권1호
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• pp.11-16
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• 2003

In this study, we investgated the effect of Red Ginseng (KRG) on liver damage induced by carbon tetrachloride (CTC) and galactosamine (GalN) in rats using indicator enzymes such as serum alanine/aspartate aminotransferases, sorbital dehydrogenase, lactate dehydrogenase, and ${\gamma}$-glutamyltransferase. Treatment of KRG restored these enzyme activities to near normal level compared to CTC or GalN treatment alone. Treatment of KRG also enhanced hepatic microsomal enzyme system, malondialdehyde formation, and depletion of reduced glutathione content, which were reduced by CTC or GalN. We also found that the decreased activities of glutathione S-transferase and glutathine reductase but not ${\gamma}$-glutamycysteine synthetase after KRG treatment restored to normal level. These results indicate that KRG has potent therapeutic activity against CTC- and GalN-induced hepatotoxicity in rat.

• Advances in Traditional Medicine
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• 제10권1호
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• pp.29-36
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• 2010

The present study was aimed to investigate the hepatoprotective and antioxidant activities of ethanol extract from Monochoria vaginalis (250 mg/kg and 500 mg/kg B/W) on acetaminophen (APAP) induced rat hepatic injury. Monochoria vaginalis is a traditional medicinal plant that is commonly used to treat and improve liver conditions in India and other Asian countries. The development of hepatotoxicity induced by APAP is promoted by oxidative stress. APAP treated group significantly (P < 0.01) elevated the serum enzymatic levels like glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, alkaline phosphatase (SALP), total bilirubin and malondialdehyde (MDA), which were restored towards normalization significantly (P < 0.01) thanol extract of yonochoria vagin is (EEMV). In addition, the EEMV significantly (P < 0.01) elevated the decreased level of total protein and antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-s-transferase and reduced glutathione. Apart from these, histopathological changes also showed the protective nature of the EEMV against APAP induced hepatic damage in liver tissues. The activity of EEMV at 500 mg/kg B/W was comparable to the standard drug silymarin (25 mg/kg B/W). In conclusion, these data suggest that the EEMV possess hepatoprotective and antioxidant effects against APAP-induced hepatotoxicity and oxidative stress in rats.