• YAKHAK HOEJI
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• v.36 no.1
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• pp.66-72
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• 1992

In order to test relationships between hepatotoxicity and transmethylation, activities of protein methylases and SAM (S-adenosyl-L-methionine)-synthetase were examined in liver tissues of rats treated with $CCl_4$. Also the concentrations of SAM and SAH were measured by HPLC in rat liver. The results are as follows. (1). Activities of protein methylases were not significantly changed in 24 hours after $CCl_4$ treatment. However, in 48 hours, activities of protein methylases were significantly increased in comparison with that of control. (2). Activity of SAM-synthetase was increased steadily in the time course after $CCl_4$ treatment. (3). S-adenosyl-L-methionine concentration of liver tissues in $CCl_4$-treated group was elevated in 24 hours, and then declined thereafter. But the SAH concentration was slightly decreased in the time course after $CCl_4$ treatment. These results indicate that SAM was very actively used in transmethylation reactions of $CCl_4$ damaged rat liver, suggesting the strong relationships between hepatotoxicity and transmethylation phenomena.

• Advances in Traditional Medicine
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• v.4 no.1
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• pp.28-36
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• 2004

The purpose of this study was to investigate the pharmacological effects of low-esterified pectin on carbon tetrachloride $(CCL_4)-induced$ hepatotoxicity in rats. The study included two experiments. In the first experiment the animals were given daily $CCL_4$ through gavage for 7 days and then 10, 50, or 250 mg/kg b.w. of pectin for 21 days. At the end of experiment rats were killed within 24 hours. The increased bilirubin level, enhanced alanine aminotransferase and aspartate aminotransferase activity in plasma induced by $CCL_4$ were partly normalized by pectin administration in a dose-dependent manner. The pectin treatment also resulted in significant recovery of $CCL_4-induced$ decrease of the liver glycogen content. In addition, pectin significantly improved $CCL_4-induced$ alterations of pro-oxidant and antioxidant biochemical parameters in liver and plasma compared to those of rats administered $CCL_4$. In the second experiment the animals were given daily 10, 50 or 250 mg/ kg b.w. of pectin for 21 days before a 7-day administration of $CCL_4$. Rats were killed 24 hours after the end of experiment. Pretreatment with pectin before $CCL_4$ administration resulted in significantly inhibited increase of the blood enzymatic activities of alanine and aspartate aminotransferases and bilirubin level in a dose-dependent manner. Also, preliminary administration of pectin prevented elevation of malondialdehyde and conjugated diene levels in liver and plasma as well as a reduction of glutathione content in liver of rats given $CCL_4$. These results suggest that low-esterified pectin exert healing and preventive effects on $CCL_4-induced$ hepatotoxicity in rats.

• Toxicological Research
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• v.24 no.4
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• pp.281-287
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• 2008

Impairment of hepatic metabolism of sulfur-containing amino acids has been known to be linked with induction of liver injury. We determined the early changes in the transsulfuration reactions in liver of rats challenged with a toxic dose of $CCl_4$ (2 mmol/kg, ip). Both hepatic methionine concentration and methionine adenosyltransferase activity were increased, but S-adenosylmethionine level did not change. Hepatic cysteine was increased significantly from 4 h after $CCl_4$ treatment. Glutathione (GSH) concentration in liver was elevated in $4{\sim}8$ h and then returned to normal in accordance with the changes in glutamate cysteine ligase activity. Cysteine dioxygenase activity and hypotaurine concentration were also elevated from 4 h after the treatment. However, plasma GSH concentration was increased progressively, reaching a level at least several fold greater than normal in 24 h. ${\gamma}$-Glutamyltransferase activity in kidney or liver was not altered by $CCl_4$, suggesting that the increase in plasma GSH could not be attributed to a failure of GSH cycling. The results indicate that acute liver injury induced by $CCl_4$ is accompanied with extensive alterations in the metabolomics of sulfurcontaining amino acids and related substances. The major metabolites and products of the transsulfuration pathway, including methionine, cysteine, hypotaurine, and GSH, are all increased in liver and plasma. The physiological significance of the change in the metabolomics of sulfur-containing substances and its role in the induction of liver injury need to be explored in future studies.

• Journal of the Korean Society of Food Science and Nutrition
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• v.22 no.6
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• pp.678-684
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• 1993

To evaluate the role of xanthine oxidase in liver damage by CCl4, a group of rats were fed tungstate for a month, which suppressed the activities of xanthine oxidase in serum and liver. Control group of rats were fed standard diet without tungstate. Liver damage was induced both in tungstate fed and control groups by two intraperitoneal injections of CCl4 at the level of 0.1ml/100g body weight at intervals of 24 hours. Increases in the levels of serum alanine aminotransferase by CCl4 were significantly smaller in tungstate fed rats than in control rats. Concomitantly, histopathologic changes were less in tungstate fed rats than in control ones. In rats either treated with CCl4 or not, hepatic type O xanthine oxidase activities were remarkably reduced by tungstate feeding. Hepatic aniline hydroxylase activities were higher in rats fed tungstate than control rats when animals were not treated with CCl4, but the enzyme activities were lower in tungstate fed rats than control when they were treated with CCl4. Neither tungstate feeding nor CCl4 treatment caused any significant changes in hepatic glutathione contents, and activities of hepatic glutathione S-transferase, glutathione peroxidase and superoxide dismutase. It is concluded xanthine oxidase reaction augment CCl4 induced liver damage via oxygen free radical system.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.30 no.6
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• pp.944-947
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• 1997

Docosahexaenoic acid (DHA) rich oil was obtained from blue fin tuna (Thunnus thynnus orientalis) orbital tissue with centrifugation of 12,000 rpm under vaccum $(10^{-1}\;Torr)\;at\;4^{\circ}C$. The effect of DHA rich oil (DHA content; $27.8\%$) on $CCl_4-induced$ acute injury was investigated biochemically and histopathologically. Dosage of DHA rich oil on 24h before $ CCl_4-administration$ prevented significantly the increase of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GTP) values. No necrosis of hepatocytes was observed in rat livers treated with DHA oil on 24h prior to $CCl_4-administration$. These results suggested that DHA oil controls the accumulation of fat in the liver and prevented the liver injury.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.7 no.1
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• pp.61-69
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• 1997

To evaluate an effect of pathological liver damage on the toluene metabolism, the rate were induced acute liver damage with 3 times $CCl_4$ injection (0.1 ml of 50 % in olive oil/100 g body wt.) three days. In the present animal molel, the injection of toluene(0.3 ml of 50 % in olive oil) showed the more decreased urine hippuric acid throughout 24 hr in the liver damage induced animals($CCl_4$-pretreated rats) than normal group. The activities of hepatic aniline hydroxylase, benzylalcohol dehydrogenase and benzaldehyde dehydrogenase were significantly decreased in $CCl_4$-pretreated rats than the normal group at 24 hr after injection of toluene. Furthermore, the benzaldehyde dehydrogenase in pooled liver of $CCl_4$-pretreated rats showed similiar $K_m$ value, but showed the more decreased $V_{max}$ value compared with the normal group by the injection of toluene. These results suggest that the rats induced liver damage with $CCl_4$ may reduce the toluene metabolism.

• YAKHAK HOEJI
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• v.54 no.1
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• pp.55-61
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• 2010

Gardenia jasminoides is one of the most widely used herbal preparations for the treatment of liver disorders. This study evaluated the potential beneficial effect of G. jasminoides in a mouse model of carbon tetrachloride ($CCl_4$)-induced liver injury. The mice were treated intraperitoneally with $CCl_4$ (10 ${\mu}l$/kg). They received G. jasminoides (30, 100, 300 mg/kg) 48 h, 24 h and 2 h before and 6 h after administering $CCl_4$. The serum activities of aminotransferase and the hepatic level of malondialdehyde were significantly higher 24 h after the $CCl_4$ treatment, while the concentration of reduced glutathione was lower. These changes were attenuated by G. jasminoides. $CCl_4$ increased the level of circulating tumor necrosis factor-$\alpha$ (TNF-$\alpha$) markedly, which was reduced by G. jasminoides. The levels of hepatic inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression were markedly higher after the $CCl_4$ treatment. G. jasminoides diminished these alterations. $CCl_4$ increased the level of TNF-$\alpha$, iNOS and COX-2 mRNA expressions, and these increases were attenuated by G. jasminoides. These results suggest that G. jasminoides alleviates $CCl_4$-induced liver injury, and this protection is likely due to the reduced oxidative stress and the downregulation of proinflammatory mediators.

• The Journal of Internal Korean Medicine
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• v.24 no.1
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• pp.55-67
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• 2003

Objective : In order to investigate the curative effect of Jucha-whan on the protective liver of guinea pigs induced by $CCl_4$ and d-galactosamine, serum transaminase(GOT, GPT), lactic dehydrogenase(LDH), alkaline phosphatase(ALP), glutathione S-transferase(GST), superoxide dismutase(SOD) were used to measure enzyme activities and lipid peroxide level. Method : The subject animals were divided into 5 groups; a control group(untreated), a subject group(administered with 0.9% Saline solution), a sample I (500mg/kg administered), sample II group (1000mg/kg administered), positive control group(administered with 200mg/kg silymarine). Result : The inhibitory effects on the serum GOT, LDH, ALP, SOD and Lipid peroxide level activities in protective liver of mice induced by $CCl_4$ were noted both in the sample I group and sample II. The inhibitory effects on the serum GPT activities in protective liver of guinea pigs induced by $CCl_4$ were noted in sample II group, but it was not noted in the sample I. The inhibitory effects on the GST activities in protective liver of guinea pigs induced by $CCl_4$ were not noted in both sample I and sample group II. The inhibitory effects on the serum GOT, GPT activities in protective liver of guinea pigs induced by d-galactosamine were noted in both sample I and sample II, but it was not recognizable statistically. The inhibitory effects on the serum LDH activities in protective liver of guinea pigs induced by d-galactosamine were noted in sample II, but it was not noted in sample I group. Conclusion : According to the above results, it is considered that Jucha-whan has treatment effects on liver injury in guinea pigs induced by $CCl_4$ and d-galactosamine. So it is required to study about the actions of mutual relation of medicines and patho-mechanism through experiment.

• The Journal of Internal Korean Medicine
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• v.24 no.1
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• pp.21-32
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• 2003

Objective : The aim of this study is to investigate the inhibitory effect of Injinchunggantang on hepatic sclerosis induced by $CCl_4$. Methods : Weight, liver function test and complete blood cell count, gross findings, and findings on liver tissue of the past(Hematoxylin & Eosin stain, Masson-Trichrome stain) were studied. Results : When it comes to the change of rats' body weight, The $CCl_{4^+}$Injinchunggantang group lost far less weight than The $CCl_{4^-}$only group. In the liver function test, which is focused on various areas such as total cholesterol, alkaline phosphotase, albumin, aspartate transaminase, alanine transaminase, The $CCl_{4^+}$Injinchunggantang group was much more closer to normal limit than the $CCl_4$ only group. In the complete blood cell count, including white blood cell, red blood cell, hemoglobin, hematocrite, platelet, The $CCl_{4^+}$Injinchunggantang group significantly closer to normal limit than $CCl_{4^-}$only group. In the gross findings of hepatic fibrosis models, Injinchunggantang showed inhibitory effect on hepatic fibrosis in the order. In the past findings of hepatic fibrosis models in Hematoxylin & Eosin, Masson-Trichrome staining, the liver in $CCl_{4^-}$only group showed atrophy and necrotic change with white nodules, whereas that of $CCl_{4^+}$Injinchunggantang group showed lesser significant change with the well_preserved tone of the tissue. In the extent of the inhibition of the hepatic fibrosis, the Injinchunggantang group showed statistically significant inhibitory effect(p<0.05) in the sclerosis model. Conclusions : These results show that Injinchunggantang have inhibitory effect on hepatic sclerosis induced by $CCl_4$ and further ultimately prevent liver cirrhosis. To obtain more credible results in this experiment, the invention of a new experimental model more similar to human hepatic sclerosis is still needed.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.3
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• pp.439-445
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• 2010

Pretreatment with Taraxacum Mongolicum H(TMH) prior to the administration of on $CCl_4$ significantly prevented the increased serum enzymatic activity of aminotransferase(ALT, AST), gamma-glutamyl transpeptidase(GGT) and bilirubin concentration in dose-dependent manner. In addition, pretreatment with TMH also significantly restored the elevation of hepatic malondialdehyde formation and the depletion of reduced glutathione content in the liver $CCl_4$-intoxicated rats. The restoration of microsomal aniline hydroxylase and aminopyrine N-demethylase activities indicated the improvement in functional status of endoplasmic reticulum. $CCl_4$-induced hepatotoxicity was also essentially prevented, as indicated by a liver histopathologic study. TMH showed antioxidant effects in $FeCl_2$-ascorbate-induced lipid peroxidation in rat liver homogenate and in superoxide radical scavenging activity. Our results suggest that the protective effect of TMH against $CCl_4$-induced hepatotoxicity possibly involve mechanisms related to its ability to block p450-mediated $CCl_4$ bioactivation and free radical scavenging effects.