• Toxicological Research
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• 제3권2호
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• pp.73-80
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• 1987

Primary cultures of adult rat hepatocytes were used to study the cytotoxicity of D-galactosamine. Hepatocytes were isolated by a collagenase perfusion technique and maintained as monolayers in serum-free medium on collagen-coated culture dishes. Treatment of galactosamine to the culture markedly inhibited the uptake of ${\alpha}$-aminoisobutyric acid (AIB) inducible with glucagon and dexamethasone. At0.1 mM of galactosamine, AIB uptake was inhibited significantly when treated for 12 hr. At higher doses (0.25, 0.5 and 1.0mM), a significant inhibition was noticed after 1 hr exposure. Generally the magnitude of the inhibition was related to the dose and treatment time of galactosamine. Treatment of galactosamine also produced a dose- and treatment time-related suppression of the tyrosine aminotransferase (TAT) induction caused by dexamethasone. Meanwhile, uptake of ouabain was not affected by the treatment of galactosamine. The viability of the hepatocytes was decreased only slightly by the treatment of galactosamine; more than 87% of the cells excluded tryphane blue when treated 1 mM galactosamine for 12 hr. Galactosamine induced depressions of AIB uptake and TAT activity were prevented by the simultaneous addition of uridine to the culture. D-Galactosamine, cytotoxicity, hepatocytes culture, ${\alpha}$-aminoisobutyric acid uptake, tyrosine aminotransferase.

• 한국식품영양학회지
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• 제25권3호
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• pp.546-553
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• 2012

This study was performed to evaluate the biological activity and protective effect of Cassia tora ethanol extracts against D-galactosamine induced hepatotoxicity in rats. Male Sprague-Dawley rats were grouped into normal group, D-galactosamine treated group(control), D-galactosamine plus 0.25% Cassia tora extracts treated group and D-galactosamine plus 0.5% Cassia tora extracts treated group. Normal and control group were fed control diet and Cassia tora extracts treated groups were fed experimental diets containing 0.25% or 0.5% Cassia tora ethanol extracts for 5 weeks. Body weight gain and liver weight of rats were not significantly different between groups. Cholesterol and triglyceride concentrations in serum and liver were significantly lower in rats treated only with D-galactosamine compared to normal group, and improved in Cassia tora extracts supplemented rats. D-galactosamine treatment significantly increased serum aspartate transaminase, alanine transaminase, gamma glutamyl transferase and alkaline phosphatase, however, the activities of aspartate transaminase and alanine transaminase were significantly decreased in Cassia tora extracts supplemented rats when compared with D-galactosamine treated control group. Cassia tora extracts significantly suppressed the D-galactosamine-induced elevation of liver thiobarbituric acid reactive substances(TBARS) contents. Superoxide dismutase activity was decreased by D-galactosamine treatment, however by the supplementation of Cassia tora ethanol extracts, significantly increased in dose-dependent manner. Glutathione peroxidase activity in rats fed diets containing Cassia tora extracts was decreased compared to control. Based on these results, we concluded that Cassia tora ethanol extracts may prevents the D-galactosamine-induced hepatotoxicity probably via an antioxidant mechanism.

• 생약학회지
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• 제31권3호
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• pp.351-356
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• 2000

The hepatoprotective effects of bergenin and its derivative, acetylbergenin, were evaluated against D-galactosamine-induced liver damage in rats. Bergenin is a C-glucoside of 4-O-methyl gallic acid that has been isolated from the cortex of Mallotus japonicus (Euphorbiaceae). Acetylbergenin was synthesized from acetylation of bergenin to increase lipophilic and physiological activities. Bergenin (50, 100 and 200 mg/kg) and acetylbergenin (25, 50 and 100 mg/kg) were administered orally once daily for successive 5 days after the injection of galactosamine (400 mg/kg, i.p.), respectively. The substantially elevated serum enzyme activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and ${\gamma}-glutamyltransferase$ due to galactosamine treatment were dose-dependently restored towards normalization by post-treatment with bergenin and acetylbergenin. Bergenin and acetylbergenin also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of reduced glutathione content induced by galactosamine in a dose-dependent manner. In addition, the decreased activities of glutathione S-transferase and glutathione reductase were restored towards normalization. These results suggest that effects of bergenin and acetylbergenin may be related to complex mechanisms that involve prevention of lipid peroxidation and preservation of hepatic glutathione. The results of this study clearly indicate that bergenin and acetylbergenin have potent hepatotherapeutic action against galactosamine-induced hepatotoxicity in rats, and lipophilic acetylbergenin is more active in the antihepatotoxic effects against galactosamine than much less lipophilic bergenin.

• 약학회지
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• 제29권1호
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• pp.43-49
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• 1985

Polysaccharides obtained from Sappan Lignum, Mori Radicis Cortex and Olibanum were examined for their liver protective effects against carbon tetrachloride-and D-galactosamine intoxication in ICR-mice. Hexobarbital sleeping time and serum transaminases (S-GOT and S-GPT) were measured as parameters for the evaluation of liver protective effects. All polysaccharides tested in this experiment showed remarkable positive effects on the prevention of hepatic intoxication with carbon tetrachloride-and D-galactosamine. Much better liver protective effects of polysaccharides were observed in D-galactosamine-liver injuries than in carbon tetrachloride-injuries.

• Applied Microscopy
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• 제40권1호
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• pp.29-35
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• 2010

본 연구는 galactosamine 투여로 인해 유발된 흰쥐의 간독성에 미치는 자초추출물의 효과를 알아보기 위해 자초 추출물을 각각 200 mg/kg과 500 mg/kg을 매일 1회씩 7일간 복강내 주사한 후, 마지막 자초 추출물 투여일에 galactosamine을 주사하여 다음과 같은 결론을 얻었다. AST, ALT, ALP, GGT와 LDH의 활성도에서는 LE200군이 GalN군에 비해 유의적으로 감소하였다. 그리고 조직학적 변화에서, GalN군은 염증세포의 침윤과 국소적인 괴사성 변화가 나타났지만, LE군들에서는 GalN 투여에 의한 변화가 상당히 경감되었다. 또한 미세구조적 변화에서는 GalN군은 미토콘드리아의 변형, 지방적의 증가, 조면소포체의 분절 등 세포소기관의 변형을 유발하였다. 그러나 LE군들에서는 대조군과 유사한 소견을 보여 주었다. 이상의 결과들로 보아, 자초추출물은 galactosamine 투여로 간독성을 유발시킨 흰쥐의 간 조직에 장애를 주지 않으면서 간독성을 완화시키는 효과가 있다고 사료된다.

• 한국식품영양학회지
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• 제9권4호
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• pp.472-477
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• 1996

간장해에 미치는 녹각의 효과를 밝힐 목적으로 녹각을 성분별로 추출 분리하여 급여하고 galactosamine으로 간장해를 유도한 후 녹각추출물이 간기능 유지에 관여하는 효소활성 및 지질 대사에 미치는 영향을 생화학적 측면에서 고찰하였다. Cytochrome P-450은 녹각추출물 급여로 증가하였으며 갈락토사민 투여로 감소하였으나 neutral-ext.군에서 높은 증가를 보였다. Glutathione peroxidase 활성은 갈락토사민 투여로 감소하였으나, 녹각 추출물 급여로 활성이 증가하였다. 간조직의 글루타티올 함량은 녹각추출물 급여로 유의적 변동이 없었으며 갈락토사민 투여로 감소하였다. 과산화지질 함량은 대조군에 비해 각각의 녹각추출물 급여군에서 감소하여 특히 water-ext. 군에서 감소정도가 가장 현저하였다. 간조직중의 총 지방질, 총 콜레스테롤 및 트리글리세리드의 함량은 대조군에 비해 각각의 녹각추출물 급여군에서 감소하였으며, water-ext.군에서 가장 많이 하게 감소하였다. 이상의 결과로 미루어 볼 때 녹각의 water-ext.과 neutral-ext.에 함유되어 있는 성분이 간기능 유지에 관여하는 효소합성 증가를 통해 활성증가를 유도하고, 이로써 독성의 대사를 촉진시키므로 간독성을 예방할 수 있을 것으로 생각되며, 이와 같은 녹각추출물의 작용이 생체에 흡수되어진 xenobiotics의 해독작용과 연관될 것으로 생각된다.

• 동국한의학연구소논문집
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• 제5권
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• pp.167-186
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• 1996

This study aimed to evaluate the protective effect of the MeoH extract of Ikhwangsan against galactosamine-induced hepatotoxicity. In the experiments, after treated with Ikhwangsan methanol extract to the rats for 15days and then induced hepatotoxicity with galactosamine for 2days. Then content of glutathione, level of lipid peroxide and activity of GOT GPT in the hepatic tissue, activity of GOT GPT ${\gamma}$-GTP ALP and ratio albumin/globulin in serum were measured. The results were obtained as followed : 1. The content of hepatic glutathione was significantly reduced by galactosamine. The test group which have been pre-treated by Ikhwangsan was confirmed considerably increased. 2. The level of hepatic lipid peroxide was increased by galactosamine. The test group which have been pre-treated by Ikhwangsan was confirmed considerably reduced. 3. The activity of GOT GPT in the hepatic tissue was significantly constrained by galactisamine. The test group which have been pre-treated by Ikhwangsan was confirmed considerably increased. 4. The activity of GOT GPT in serum was increased by galactosamine. The test group which have been pre-treated by Ikhwangsan was confirmed considerably reduced. 5. The activity of ${\gamma}$-GTP in serum was increased by galactosamine. The test group which have been pre-treated by Ikhwangsan was reduced. 6. The activity of ALP in serum was increased by galactosamine. The test group which have been pre-treated by Ikhwangsan was confirmed considerably reduced. 7. The ratio albumin/globulin in serum was reduced by galactosamine. The test group which have been pre-treated by Ikhwangsan was increased.

• 약학회지
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• 제37권4호
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• pp.383-388
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• 1993

Pharmacokinetics of aucubin, an irdoid glucoside, was compared in rats of experimental hepatic failure(EHF). EHF was induced by CCI$_{4}$ or D-galactosamine pretreatment. This work was designed to find out any differences in the pharmacokinetics of aucubin that may explain the different protective effect of aucubin on CCI$_{4}$- and galactosamine-induced EHF : aucubin reportedly protected CCI$_{4}$-inducing hepatotoxicity effectively, but did not for galactosamine-hepatotoxicity. EHF was induced by intraperitoneal injection Of CCI$_{4}$(0.9ml/kg) or galactosamine(250 mg/kg) to Wistar rats 24 hr before the pharmacokinetic study. The rats were fasted during the 24 hr. Aucubin was iv injected at a dose of 15 mg/kg and the plasma aucubin was assayed by HPLC. There were no significant differences in the pathophysiologies(body weight, liver weight, GTP, hematocrit, blood cell distrbution and plasma protein binding of aucubin) between the two EHF models except GOP which was significantly (p<0.05) higher in CCI$_{4}$-than in galactosamine-EHF. On the other hand, pharmacokinetics of aucubin such as total cleatance(CL$_{t}$), distribution volume at steady-state(Vd$_{ss}$), and mean residence time(MRT) differed significantly(p<0.05) between the models : for example, CL$_{t}$ was increased two fold by CCI$_{4}$, but not by galaclosamine ; Vd$_{ss}$, in galactosamine-EHF was higher than that in CCI$_{4}$-EHF ; MRT was decreased by CCI$_{4}$, but increased conversely by galactosamine. The increase of CL$_{t}$(and decrease of MRT) in rats of CCI$_{4}$-EHF was contrary to the general expectation for the hepatic failure : most of the hepatic failures have been known to decrease CL$_{t}$ of the administered drugs. Whether the difference in the pharmacokinetics is responsible for the different protective effect of aucubin against the two EHF models is of interest. However, much more studies on biliary excretion, urinary excretion, and hepatic uptake in cellular level should be preceded before any conclusions are made on the role of different pharmacokinetics on the different pharmacology of aucubin.

• 대한한방내과학회지
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• 제21권2호
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• pp.267-274
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• 2000

Objectives : In order to investigate the curative effect of Daesihotang-sosunggitang-gagambang on the liver injury of rats induced by $CCl_4$ and d-galactosamine. Methods : All animals were divided into 5 groups, those were normal group(untreated), control group(administrated with 0.9% Saline solution), sample I group(65mg/kg administrated), sample II group(130mg/kg administrated), positive control group(administrated with 200mg/kg silymarine). After the liver injury of rats induced by ccl4 and d-galactosamine, and cheked the serum transaminase(GOT, GPT) alkaline phosphatase(ALP), lactic dehydrogenase(LDH) for enzyme activities and triglyceride, total cholesterol amounts for serum component were measured. Result : The inhibitory effects on the serum GOT, GPT, LDH, ALP activities, serum total cholesterol content level in liver injury of rats induced by ccl4 were noted in both sample I group and sample II group. The inhibitory effects on the serum GPT, LDH activities and serum total cholesterol content level in liver injury of rats induced by d-galactosamine were noted in both sample I group and sample II group. The inhivitory effects on the serum GOT activities and triglyceride content level in liver injury of rats induced d-galactosamine were noted in sample I group, but it is not recognizable statistically. In sample II, they were noted. Conclusions : Deesihotang-sosoonggitang-gagambang has treatment effect against liver injury in rats induced by ccl4 and d-galactosamine. So it is required to study about the actions of mutual relation of medicines and path-mechanism by experiment.

• 대한본초학회지
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• 제20권2호
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• pp.127-136
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• 2005

Objectives : The present study attempted to reveal the effects of the combination of Fel Ursi and Bezoar on the improvement of the function of the liver, through examining the effects of Fel Ursi, Bezoar, and Woong-Whang Tang composed of Fel Ursi and Bezoar. Method : Acute hepatitis was induced by galactosamine to rats, and then Fel Ursi, Bezoar Bovis, and Woong-Whang Tang were introjected to measure the influence of serums such as AST, ALT, ALP, ${\gamma}GT$, and lipid peroxide of liver tissues which are considered as the index of the function of the liver. Results : 1. Fel Ursi decreased the lipid peroxide of ALT, ${\gamma}FT$, and liver tissue and that of mitochondria in liver tissues of the rats with galactosamine-induced acute hepatitis, but it did not have any significant effect on AST and ALP. 2. Bezoar Bovis decreased the lipid peroxide of AST, ALT, ALP, ${\gamma}GT$, and the liver tissues among serum of the rats suffering from acute hapatitis induced by galactosamine, but it did not have any significant effect on that of mitochondria of the liver tissues. 3. Woong-Whang Tang had a significant effects on the lipid peroxide of AST, ALT, ALP, ${\gamma}GT$, and the liver tissues, and on the decrease of lipid peroxide of mitochondria, among serum of the rats suffering from acute hapatitis induced by galactosamine. Conclusion : Fel Ursi and Bezoar Bovis were judged to be effective on the acute hepatitis of the liver by galactosamine. In particular, Woong-Whang Tang which was composed of the combination of Fel Ursi and Bezoar Bovis was more efficient in the improvement of the function of the liver and the amount of lipid peroxide than the respective use of Fel Ursi or Bezoar Bovis.