• Archives of Pharmacal Research
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• 제16권1호
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• pp.13-17
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• 1993

Several naturally occurring furanocoumarins significantly inhibited microsomal lipid peroxidation not only mediated by endogeneous iron and NADPH but also initiated by $CCL_4$ metabolites, phellopterin, a potent inhibibitor of cytochrome p-450, exhibited an almost complete inhibition of $CCL_4$-induced hepatotoxicity as measured by sGPT activity 24 hr after $CCL_4$ intoxication, whereas other furanocoumarins such as imperation, byakangelicin and oxypeucedanin methanolate exerted no protective effect. When compared with other cytochrome P-450 inhibitors(SKF-52A, AIA) and silymarin given at the same dose level $(ED_{50})$, phellopterin still showed a significant inhibition of hepatotoxicity which was even stronger than that of AIA, known as a typical suicide inhibitor. Phellopterin was partially effective when given 30 min after $CCL_4$ treatment. Repeated administrations of phellopterin, however, resulted in a complete loss of the protection against $CCL_4$-induced hepatotoxicity.

• Food Science and Biotechnology
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• 제15권5호
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• pp.752-755
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• 2006

This study was carried out to investigate the effects of ash tree leaf extract (ALE) on acetaminophen (APAP)-induced hepatotoxicity in mice. Hepatoprotective effects were detected by biochemical analysis of hepatic enzymes and histopathological examination of the liver. BALB/c mice were divided into three groups: 'normal' control mice, APAP-treated control mice, and mice pretreated with ALE and treated with APAP. A single dose of APAP markedly increased levels of plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Light micrographs of liver cells stained with hematoxylin and eosin showed that APAP induced severe centrilobular necrosis, degeneration, and infiltration by inflammatory cells. Moreover, APAP caused the numbers of TUNEL-positive hepatocytes to increase and caused glycogen content to decrease as observed by Periodic acid-Schiff stain. However, pretreatment with ALE for 7 days prior to the administration of APAP significantly decreased plasma levels of AST and ALT. Histological findings demonstrated that ALE pretreatment alleviated APAP-induced liver damage, and induced the regeneration of liver tissue and restoration of glycogen. These results indicate that ash tree leaf extract exerts a protective effect against APAP-hepatotoxicity induced injury.

• Environmental Analysis Health and Toxicology
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• 제17권2호
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• pp.161-174
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• 2002

To investigate effects of A. gmelini on the 14-day CCl$_4$induced hepatotoxicity, extracts were prepared in 3 ml saline at the dose of 5,000 mg/kg b.w. to administer orally once daily. Each concentration (5：5, 2：5 : 7.5, 1：9, CCl$_4$: olive oil v/v) of CCl$_4$was orally administered with 2.5 ml/kg b.w., During the experiment, halves of the rats were sacrificed every 7 day and hemanalysis was done. On the 7th day, hemanalysis showed following recovery values; AST 52.6∼61.4％, ALT 55.9∼86.1％, ALP 46.0∼70.9%, BUN 75.7∼100.0< ％, TBIL 55.2∼96.1％, TCHO 38.0∼63.7％, and TG 55.2∼96.0％. On the 14th day, recovery values of each treatment were GOT 37.7∼43.1％, GPT 19.8∼45.9％, ALP 58.1∼95.9％, BUN 57.6∼100.0< ％, TBIL 78.6∼100.0< ％, TCHO 56.9∼100.0< ％, and TG 10.0∼5l.2%. By histological examination of liver, hydropic degeneration, fatty change, lipid accumulation and necrosis were also recovered by administration of A. gmelini extract.

• 대한약침학회지
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• 제10권1호통권22호
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• pp.101-107
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• 2007

Objectives : This study was aimed at investigating liver protection mechanism of Cultivated Ginseng and Cultivated Wild Ginseng of Korean and Chinese by inducing liver toxicity through $CCl_4$ and t-BHP in mice and evaluated serological findings. Methods : Experiment groups was categorized into untreated normal group, treated control group, and orally administered Cultivated Ginseng and Cultivated Wild Ginseng of Korean and Chinese experimental groups. At the termination of experiment, gross examination of the liver as well as Total bilirubin, AST, and ALT contents in the serum were evaluated. Results : 1. In the $CCl_4$ induced acute hepatotoxicity test, total bilirubin, AST and ALT didn't show significant differences between the control and experimental groups. 2. In the t-BHP induced acute hepatotoxicity test, total bilirubin, AST and ALT didn't show significant differences between the control and experimental groups. Conclusion : Taken together, Cultivated Ginseng and Cultivated Wild Ginseng of Korean and Chinese cannot be effectively used for recovering the liver functions in acute hepatotoxicity tests using $CCl_4$ and t-BHP. Further researches, for example treated long period, must be tried to verify the efficacies.

• 대한한의학방제학회지
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• 제8권1호
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• pp.129-146
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• 2000

This study was carried out to investigate the effects of Solanum lyratum Extract (SLE) on the recovery of liver in $CCI_{4}-intoxicated$ mice. In this study, ICR-Mice were divided into 3 experimental groups; Normal group was fed basal diet and was fed bassal diet for 2 Weeks, sample group was injected $CCl_{4}\;(0.6m{\ell}/kg)$ and was fed basal diet for 2 weeks, sample group was injected $CCl_{4}\;(0.6m{\ell}/kg)$ and was fed the SLE 500mg/kg fod 2 Weeks. In sample group, the level of serum AST, ALT, ALP activity decreased significantly compared with control group. This results suggest that SLE has appreciable therapeutic effect on $CCI_4$ induced hepatotoxicity. In sample group, the level of LPO in liver homogenates decreased significantly compared with control group. In sample group. the level of GSH, catalase in liver homogenates increased significantly compared with control group. This results suggest that SLE has appreciable antioxidant effect on $CCI_4induced hepatotoxicity. In conclusion the results suggest that SLE has appreciable therapeutic effect and antioxidant effect on $CCI_4$ induced hepatotoxicity.

• 대한의생명과학회지
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• 제10권4호
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• pp.447-452
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• 2004

This study was designed to investigate the effect of Codonopsis lanceolata extracts on carbon tetrachloride (CCl₄)­induced hepatotoxicity in rats fed high, medium or low fat diet. The liver weight was increased not by the level of fat in diet but by administration of CCl₄. Activities of serum aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were significantly increased by CCl₄, the activities of AST and alanine aminotransferase (ALT) were significantly decreased in case of CCl₄ treatment with C. lanceolata extracts. In high fat diet with CCl₄ administration, the content of total lipid in liver was significantly increased, which was significantly decreased by the administration of C. lanceolata extracts. Administration of C. lanceolata water extracts remarkably prevented the tissue injury such as lipid degeneration, infiltration of inflanunatory cells and necrosis caused by CCl₄, but those methanol extracts did not affect histopathological changes of the liver as water extract. The data suggest that intake of C. lanceolata extracts would prevent lipid accumulation and hepatotoxicity induced by high fat diet and CCl₄ abministratim, and the water extract of C. lanceolata is supposed to be more effective than those methanol extract.

• 약학회지
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• 제36권1호
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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.

• 약학회지
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• 제36권1호
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• pp.80-86
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• 1992

Streptozotocin (STZ) is a naturally occurring nitrosoamide used extensively to produce diabetes in experimental animals. Our previous study has demonstrated that i.v. administraton of streptozotocin induces significant red blood cell hemolmysis in rats. Since it has been reported that the highest concentration of STZ is found in the liver, the effect of STZ in freshly isolated rat hepatocytes has been investigated. STZ treatment (10 mM) did not cause significant loss of viability throughout 4 hour incubation, while high dose of STZ (300 mM) to hepatocytes resulted in complete cell death within 3 hours. Addition of 40 mM glucose to incubation medium did not potentiate STZ-induced hepatotoxicity, suggesting that STZ-induced hyperglycemia in vivo did not affect its hepatotoxicity. To investigate the mechanixm of the toxicity, intracellular total glutathione level was determined. Tratment with 10 mM STZ which was not toxic to hepatocytes led to complete depletion of intracellular glutathione level within 1 hour incubation. These results suggest that STZ-induced hepatotoxicity may be independent on the intracellular glutathione depletion.

• 약학회지
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• 제37권5호
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• pp.499-503
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• 1993

Betaine, a major component of Lycii Fructus, was evaluated for its anti-hepatotoxic activity on carbon tetrachloride-induced hepatotoxicity in primary cultured rat hepatocytes. Betaine was found to attenuate carbon tetrachloride-induced hepatotoxicity both morphologically and biochemically. Typical hepatocyte necrosis due to carbon tetrachloride seemed to be reduced by 50 to 500 $\mu{M}$ of betaine under microscopical observation. The value of glutamic pyruvic transaminase released from the hepatocytes into the medium significantly decreased as betaine concentration increased. Betaine also significantly elevated the reduced activities of some enzymes, cytochrome P-450, 7-ethoxycoumarin-0-deethylase and glutathione-S-transferase, involved in xenobiotic metabolism due to carbon tetrachloride-induced hepatotoxicity. These results demonstrate a possible hepato-protective role of betaine against fatty liver that could be easily induced by carbon tetrachloride.

• 생약학회지
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• 제30권1호
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• pp.12-17
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• 1999

The youngkaechulgamtang (Y) composed of four herb drugs, including Hoelen (H). Cinnamomi Ramulus (C). Atractylodis Rhizoma Alba (A) and Glycyrrhizae Radix (G). In oriental medicine literatures, Youngkaechulgamtang is described to be effective in headache, inflammation, uremia, gastritis, diarrhea and hypertension. To estimate the clinical effectiveness of Youngkaechulgamtang, several pharmacological experiments were carried out. The results are summerized as follows; On acetaminophen-induced hepatotoxicity, C+A, Y-G, Y-H, MIX and Y showed the significant elevation of glutathione-S-transferase. But, C+A, Y-G, Y-H, MIX and Y showed the significant suppression of serum aminotransferases. On ANIT-induced cholestasis, U (Ursodesoxycholic acid 50 mg/kg)+$Y_l$ (760 mg/kg) showed the significant increase of bile juice volume. $Y_l,\;Y_2$ (1520 mg/kg), U, $U+Y_l$ showed the remarkable increase of cholic acid. U and $U+Y_l$ showed the significant decrease of total bilirubin. From these results, it is suggest that Y shows liver protective effect against various hepatic injury. Especially, Youngkaechulgamtang was more effective than mixture of 4 ingredients in the elevation of glutathione-S-transferase in acetaminophen-induced hepatotoxicity.