• Toxicological Research
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• 제9권2호
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• pp.253-262
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• 1993

The effects of dichloromethane (DCM) on carbon tetrachloride (CT) toxicity were examined in adult male rats. A concomitant treatment of rats with DCM (0.3, 0.6, 1.2 g/kg, po) significantly potentiated the hepatotoxicity of CT (1.0 g/kg, po) as determined by increase in serum GPT (glutamic pyruvic transaminase), GOT (glutamic oxaloacetic transaminase), and SDH (sorbitol dehydrogenase) activity 24 hr following the treatments. Serum LDH (lactate dehydrogenase) activity was increased by either DCM or CT treatment.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.212.2-212.2
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• 2003

Primary cultured rat hepatocytes injured by carbon tetrachloride as a model to screen for hepatoprotective effect. Four flavonoid compounds showed anti-hepatotoxic effect by decrease GPT. LDH activity and MDA level. Also screen for hepatoprotective, anti-oxidative and anti-apoptosis effects of baicalin and baicalein on chang cell treated with t-BHP. Mesured radical detoxifying enzyme, GST and antioxidant enzyme SOD, Catalase activity, GSH level and Cellular glutathion peroxidase activity. (omitted)

• 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.

• 한방비만학회지
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• 제9권1호
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• pp.59-69
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• 2009

Objectives This study was designed to evaluate the difference of between Kyungohkgo and Kyungohkgo Ga Nokyong effects of growth Methods We divided male Spraque-Dawley rats into 6 groups. They were Normal group, Growth deficiency rat with insufficient nutrition diet group, Growth deficiency rat with 0.1% Kyungohkgo group, Growth deficiency rat with 0.2% Kyungohkgo group, Growth deficiency rat with 0.1% Kyungohkgo Ga Nokyong group and Growth deficiency rat with 0.2% Kyungohkgo Ga Nokyong group. They were administered for 5 weeks. We measured body weight, serum growth hormone, insulin-like growth factor and thyroid stimulating hormone, RBC, concentration of Hb and PCV ratio, total WBC and its composition, the values of plasma glutamic oxaloacetic transaminase(GOT) and glutamic pyruvic transaminase(GPT) activities. Results 1. In body weight, Kyungohkgo 0.1%, Kyungohkgo Ga Nokyong 0.1%, 0.2% groups were showed sighnificantly different than control group. But That groups were not showed significantly different than each others. 2. In serum growth hormone, insulin-like growth factor and thyroid stimulating hormone, we obtained the results of tendency to increase in Kyungohkgo Ga Nokyong group, however these values showed no significantly different. 3. In the counts of RBC, Kyungohkgo group and Kyungohkgo Ga Nokyong group were showed significantly different than control group. But these values showed no significantly different. In the concentration of Hb, Kyungohkgo Ga Nokyong 0.2%group was showed significantly different than control group. Kyungohkgo Ga Nokyong 0.2% group and Kyungohkgo 0.2% group were showed significantly different than control group. 4. The counts of total WBC and its composition showed no significantly different in all treatment groups. 5. The values of plasma glutamic oxaloacetic transaminase(GOT) and glutamic pyruvic transaminase(GPT) activities showed no significantly different in all treatment groups. Conclusions So Kyungohkgo Ga Nokyong and Kyungohkgo have an effect of promoting growth of rats. And We know that the effect of Kyungohkgo Ga Nokyong is better than Kyungohkgo.

• Journal of Pharmaceutical Investigation
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• 제36권1호
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• pp.19-22
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• 2006

The pharmacokinetics of nimodipine, following a single 16 mg/kg oral dose, was investigated in rabbits with hepatic failure induced by 0.5 mL/kg (mild), 1.0 mL/kg (moderate) and 2.0 mL/kg (severe) of carbon tetrachloride $(CCl_{4}$ : olive oil = 20 : 80, v/v). The plasma concentrations of nimodipine were determined by a high performance liquid chromatographic assay. The levels of sGOT and sGPT in rabbits with mild $(86.2{\pm}29.0\;and\;98.5{\pm}33.1\;unit/dL)$, moderate $(168.1{\pm}61.2\;and\;196.2{\pm}66.0\;unit/dL)$ and severe $(292.7{\pm}82.2\;and\;314.2{\pm}99.8\;unit/dL)$ hepatic failure were significantly increased compared to the control $(38.0{\pm}10.1\;and\;32.4{\pm}10.2\;unit/dL)$. The area under the plasma concentration-time curve (AUC) of nimodipine was significantly increased in mild $(131.7{\pm}28.1%)$, moderate $(168.8{\pm}32.8%)$ and severe $(204.6{\pm}58.3%)$ carbon tetrachloride-induced hepatic failure rabbits compared to the control (100%) rabbits. The volume of distribution $(V_{d})$ and the total body clearance $(CL_{t})$ of nimodipine were significantly decreased in all hepatic failure groups. The elimination rate constant $(K_{el})$ of nimodipine was significantly decreased in moderate and severe carbon tetrachloride-induced hepatic failure rabbits. There was a correlation between sGOT (y= 1.01x+241, r=0.993) or sGPT (y=0.92x +243, r=0.997) value and the AUC of nimodipine in the rabbits with hepatic failure. These findings suggest that the hepatic metabolism of nimodipine was inhibited by carbon tetrachloride-induced hepatic failure rabbits, resulting in the decrese in $V_{d}$ and $CL_{t}$ of nimodipine in the rabbits with mild, moderate and severe hepatic failure.

• Journal of Acupuncture Research
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• 제22권3호
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• pp.53-67
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• 2005

기문혈(期門穴)에 대한(對) 오공자약침(蜈蚣雌藥鍼)이 D-Galactosamine에 의하여 유발된 간손상(肝損傷)에 미치는 영향을 실험적으로 규명하고자 흰쥐에게 약침을 처치한 후 혈청내의 G0T GPT, ${\gamma}$-GTP, Total bilirubin, LDH, ALP, Total cholesterol, Triglyceride 및 혈 액액내의 WBC, RBC, HGB, Hct 등을 관찰한 바 다음과 같은 결과를 얻었다. 1. GPT변화에서 대조군에 비하여 SHA-2군과 SHA-3군이 유의한 감소를 보였다. 2. Total bilirubin변화에서 대조군에 비하여 SHA-1군, SHA-2군과 SHA-3군이 유의한 감소를 보였다. 3. ${\gamma}$-GTP변화에서 대조군에 비하여 SHA-1군 과 SHA-2군이 유의한 감소를 보였다. 4. Total cholesterol변화에서 대조군에 비하여 SHA-2 군이 유의한 증가를 보였다. 5. Triglyceride변화에서 대조군에 비하여 SHA-1군, SHA-2군과 SHA-3군이 유의한 감소를 보였다. 6. HDL-cholesterol변화에서 대조군에 비하여 SHA-2군이 유의한 증가를 보였다. 7. 혈액내 변화에서 대조군에 비하여 WBC는 SHA-2군에서 유의한 감소를 보였으며, RBC는 SHA-2군과 SHA-3군에서 유의한 증가를 보였고, HGB는 SHA-2군과 SHA-3군에서 유의한 증가를 보였으며, Hct는 SHA-3군에서 유의한 증가를 보였다. 이상의 실험결과를 종합해보면 오공약침이 D-galactosamine으로 유발된 백서의 간손상에 효과적이라고 생각되며 간손상에 대한 예방, 치료적인 부분에서 향후 지속적인 연구가 필요하리라고 사료된다.

• Molecular & Cellular Toxicology
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• 제5권4호
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• pp.273-282
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• 2009

Cadmium (Cd) and tributyltin (TBT) are common contaminants of marine and freshwater ecosystems, and can induce the formation of reactive oxygen species (ROS). These ROS can, in turn, cause oxidative stress. In the present study, we investigated time-related effects of Cd (0.05 and 0.1 ppm) and TBT (5 and 10 ppb) treatment on antioxidant enzyme activity, i.e., the activity of superoxide dismutase (SOD) and catalase (CAT) in the gills and digestive glands of the ark shell, Scapharca broughtonii. In addition, hydrogen peroxide ($H_2O_2$) concentrations, lysozyme activity, and glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) levels were measured in the hemolymph. We found that Cd and TBT treatment significantly increased antioxidant enzyme mRNA expression and activity in the digestive glands and gills in a time-dependent manner. In response to the Cd and TBT treatments, antioxidant enzymes mRNA expression and activity increased up to day 5 in the digestive glands and then decreased by day 7. In the gills, antioxidant enzymes mRNA expression and activity increased up to day 3 and then decreased by day 5. Likewise, $H_2O_2$ concentrations significantly increased up to day 5 and then decreased by day 7. Finally, lysozyme activity decreased during the experimental period, whereas GOT and GPT levels were significantly increased in a time-dependent manner. These results suggest that antioxidant enzymes play an important role in decreasing ROS levels and oxidative stress in ark shells exposed to Cd and TBT.

• 한국식품영양과학회지
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• 제38권11호
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• pp.1499-1505
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• 2009

본 연구는 김치에서 분리한 GABA 생성능이 우수한 젖산균을 이용하여 알코올 투여 흰쥐의 간 기능 개선에 미치는 영향을 조사하였다. 실험동물의 체중 및 식이섭취량, 혈청 및 간 지질농도, 간 질환과 관련된 혈청 및 간 효소 활성, 혈중 에탄올 농도, 항산화 효소 활성을 측정한 결과는 다음과 같다. 체중 및 식이섭취량은 각 그룹간의 유의적인 차이를 나타내지 않았으며 각 기관 무게도 군 간의 유의적인 차이를 나타내지 않았으나 정상식이 섭취 군에 비해 알코올 투여 군에서 체중과 식이섭취량이 약간 감소하는 경향을 보였다. 알코올 섭취로 인해 높아진 혈중 총 콜레스테롤 및 중성지질은 젖산균 GABA 파우더투여 군에서 유의적인 차이를 보이며 정상식이 군과 비슷한 수준으로 낮아졌다. 또한 HDL-cholesterol은 군 간의 차이를 보이지는 않았으나, 알코올투여 군에 비해 높아지는 경향을 보였다. 간의 총콜레스테롤 농도는 군 간의 유의적인 차이는 없었으나, 중성지질 농도는 실험군 간의 현저한 차이를 보이며 알코올 투여 군에 비해 젖산균 GABA 파우더 투여 군에서 정상식이 군과 비슷한 수준으로 낮아졌다. 혈중 효소활성 GOT, GPT는 알코올투여 군에 비해 젖산균 GABA 파우더투여 군에서 유의적인 차이를 보이며 정상수준으로 낮아졌으며, 간 GOT는 젖산균 GABA 파우더투여로 인해 현저한 차이를 보이며 알코올투여 군에 비해 낮아졌다. GPT는 각 그룹 간 유의적인 차이를 보이지 않았다. 혈중 알코올 농도를 시간별(0분, 30분, 60분, 120분, 240분, 360분)로 측정한 결과 그룹간의 유의적인 차이를 나타내지 않았으나 젖산균 파우더투여 군에서 알코올 대사를 촉진하는 경향을 보였다. 각 그룹간의 간 조직 중 SOD 활성은 알코올투여 군에 비해 젖산균 파우더투여 군과 젖산균 GABA 파우더 투여 군에서 유의적으로 높은 SOD 수준을 나타내었다. 본 실험을 통해 김치에서 분리한 젖산균 OPK2-59 GABA 파우더가 혈중 총 콜레스테롤과 중성지질, 간의 중성지질 농도를 유의적으로 감소시키고, 혈중 GOT, GPT, 간 GOT 효소활성 감소, 알코올대사 촉진, 항산화 효소활성을 상승시키는 효과를 확인하였다. 이는 김치유래의 젖산균 OPK2-59 GABA 파우더가 알코올투여 흰쥐의 지방대사 및 간 기능을 개선시키는데 기여할 수 있음을 보여주는 것으로, 향후 이러한 효능에 대한 심도 있는 기작연구와 더불어 다른 효능에 대한 연구가 기대된다. 또한 본 젖산균을 김치발효용 스타터로 활용하여 기능성식품을 개발하게 된다면 우수한 전통생물자원을 이용하여 국민건강 증진에 크게 기여할 수 있을 것으로 사료된다.

• 대한한의학방제학회지
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• 제12권2호
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• pp.139-154
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• 2004

Acetaminophen은 세계적으로 널리 사용되는 해열 진통제이지만, 또한 과용 및 남용, 알코올 중독과 같은 여러 원인에 의해 간독성을 유발할 수 있는 약물이다. 이러한 acetaminophen의 간독성은 CYP에 의해 생성되는 대사산물인 NAPQI와 활성산소에 의해 유발되는 것으로 알려져 있다. 본 연구에서 5주된 수컷 백서에 acetaminophen (500 mg/kg)을 투여하기 전에 대시호탕 (500 mg/kg)를 일주일간 투여하였다. 이후 GOT, GPT, GST 그리고, 조직사진으로 대시호탕의 간보호작용을 측정하였다. 또한 대시호탕의 간보호작용 기전을 항산화작용과 CYP 2E1 발현조절을 통한 NAPQI 생성억제의 두 가지 면에서 측정하였다. GOT, GPT 그리고 조직사진에서 나타난 결과들은 대시호탕이 고용량의 acetaminophen에 대한 간보호작용이 있음을 증명할 수 있었다. 또한 LPO와 catalase, 그리고 GSH 실험에서 나타난 결과들을 통해 대시호탕이 항산화작용이 있음을 알 수 있었다. 그리고 GSH, GST, RT-PCR, western blot 실험에서 대시호탕이 CYP 2E1의 발현을 조절하여 NAPQI 생성을 억제한다는 것도 알 수 있었다. 이상의 결과들을 바탕으로 대시호탕은 항산화작용에 의한 활성산소 제거력과 CYP 2E1의 발현조절을 통한 NAPQI 생성억제로 고용량 acetaminophen에 의해 유도된 간손상에 대해 유의성 있는 보호작용을 한다는 것을 알 수 있었다.

• Nutrition Research and Practice
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• 제3권2호
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• pp.95-101
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• 2009

It has been reported that dietary polyunsaturated fats (PUFA) increase liver injury in response to ethanol feeding. We tested the hypothesis that diets rich in linoleic acid (18:2n-6) would affect acute liver injury after acetaminophen injection and that protein restriction might exacerbate the liver injury. We examined effects of feeding diets with either 15% (wt/wt) corn oil or 14% beef tallow and 1% corn oil for six weeks with either 6 or 20 g/100 g protein on acute hepatotoxicity. After the feeding period, liver injury was induced by injecting either with 600 mg/kg body weight acetaminophen suspended in gum arabic-based vehicle, or with vehicle alone during fasting status. Samples of liver and plasma were taken for analyses of hepatic glutathione (GSH) levels and liver-specific enzymes [(Glutamate-pyruvate transaminase (GPT) and glutamate-oxaloacetate transaminase (GOT)], respectively. Whereas GSH level was significantly lower in only group fed 15% corn oil with 6 g/100 g protein among acetaminophen-treated groups, activities of GPT and GOT were significantly elevated in all groups except the one fed beef tallow with 20 g/100 g protein, suggesting low protein might exacerbate drug-induced hepatotoxicity. The feeding regimens changed the ratio of 18:2n-6 to oleic acid (18:1n-9) in total liver lipids approximately five-fold, and produced modest changes in arachidonic acid (20:4n-6). We conclude that diets with high 18:2n-6 promote acetaminophen-induced liver injury compared to diets with more saturated fatty acids (SFA). In addition, protein restriction appeared to exacerbate the liver injury.