• Biomolecules & Therapeutics
• /
• v.20 no.4
• /
• pp.406-412
• /
• 2012

This study was performed to examine the hepatoprotective effect of isorhamnetin-3-O-galactoside, a flavonoid glycoside isolated from Artemisia capillaris Thunberg (Compositae), against carbon tetrachloride ($CCl_4$)-induced hepatic injury. Mice were treated intraperitoneally with vehicle or isorhamnetin-3-O-galactoside (50, 100, and 200 mg/kg) 30 min before and 2 h after $CCl_4$ (20 ${\mu}l/kg$) injection. Serum aminotransferase activities and hepatic level of malondialdehyde were significantly higher after $CCl_4$ treatment, and these increases were attenuated by isorhamnetin-3-O-galactoside. $CCl_4$ markedly increased serum tumor necrosis factor-${\alpha}$ level, which was reduced by isorhamnetin-3-O-galactoside. The levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and heme oxygenase-1 (HO-1) protein and their mRNA expression levels were significantly increased after $CCl_4$ injection. The levels of HO-1 protein and mRNA expression levels were augmented by isorhamnetin-3-O-galactoside, while isorhamnetin-3-O-galactoside attenuated the increases in iNOS and COX-2 protein and mRNA expression levels. $CCl_4$ increased the level of phosphorylated c-Jun N-terminal kinase, extracellular signal-regulated kinase and p38, and isorhamnetin-3-O-galactoside reduced these increases. The nuclear translocation of nuclear factor kappa B (NF-${\kappa}B$), activating protein-1, and nuclear factor erythroid 2-related factor 2 (Nrf2) were significantly increased after $CCl_4$ administration. Isorhamnetin-3-O-galactoside attenuated the increases of NF-${\kappa}B$ and c-Jun nuclear translocation, while it augmented the nuclear level of Nrf2. These results suggest that isorhamnetin-3-O-galactoside ameliorates $CCl_4$-induced hepatic damage by enhancing the anti-oxidative defense system and reducing the inflammatory signaling pathways.

• The Korean Journal of Nuclear Medicine
• /
• v.5 no.2
• /
• pp.19-40
• /
• 1971

Since the iron balance is maintained by regulated intestinal absorption rather than regulated excretion, there have been many reports concerning the factors which may influence the intestinal iron absorption. As the liver is the largest iron storage organ of the body, any hepatocellular damage may result in disturbances in iron metabolism, e,g., frequent co-existence of hemochromatosis and liver cirrhosis, or elevated serum iron level and increased iron absorption rate in patients with infectious hepatitis or cirrhosis. In one effort to demonstrate the influence of hepatocellular damage on intestinal iron absortion, the iron absorption rate was measured in the rabbits whose livers were injured by a single subcutaneous injection of carbon tetrachloride (doses ranging from 0.15 to 0.5cc per kg of body weight) or by a single irradiation of 2,000 to 16,000 rads with $^{60}Co$ on the liver locally. A single oral dose of $1{\mu}Ci\;of\;^{59}Fe$-citrate with 0.5mg of ferrous citrate was fed in the fasting state, 24 hours after hepatic damage had been induced, without any reducing or chelating agents, and stool was collected for one week thereafter. Serum iron levels, together with conventional liver function tests, were measured at 24, 48, 72, 120 and 168 hours after liver damage had been induced. All animals were sacrificed upon the completing of the one week's test period and tissue specimens were prepared for H-E and Gomori's iron stain. Following are the results. 1. Normal iron absorption rate of the rabbit was $41.72{\pm}3.61%$ when 0.5mg of iron was given in the fasting state, as measured by subtracting the amount recovered in stool collected for 7 days from the amount given. The test period of 7 days is adequate, for only 1% of the iron given was excreted thereafter. 2. The intestinal iron absorption rate and serum iron level were significantly increased when the animal was poisoned by a single subcutaneous injection of 0.15cc. per kg. of body weight of carbon tetrachloride or more, or the liver was irradiated with a single dose of 12,000 rads or more. The results of liver function tests which were done simultaneously remained within normal limit except SGOT and SGPT which were somewhat increased. 3. In each case, there has been good correlation between the extent of liver cell damage and degree of increased iron absorption rate or serum iron level. 4. The method of liver damage appeared to make no obvious difference in the pattern of iron deposit in liver. This may be partly due to the fact that tissue specimens were obtained too late, for by this time the elevated serum iron level had returned within normal range and the pathological changes were almost healed. 5. The possible factors and relationship between intestinal iron absorption and hepatic parenchymal cell damage has been discussed.

• Journal of the Korean Society of Food Culture
• /
• v.3 no.4
• /
• pp.377-383
• /
• 1988

This studies have been carried out to develop Korean traditional tea from the effects of Cornus officinalis and Lycium chinense and to study the developed tea on microbiological (Saccharomyces cerevisiae) and metaboilsm of experimental animals (Spraque-Duwely male rats 200g). On the microbiological study the yeast growth is increased with the increase of added Cornus officinalis or Lycium chinense and Lycium chinense increased the yeast growth more than Cornus officinalis, especially the synergistic effects are recognized on mixed extract of Lycium chinense and Cornus officinalis. The effects of Cornus officinalis, Lycium chinense or the mixed extract of both extract on liver damage caused by carbon tetrachloride were investigated in the case of animal test. The activities of GOT and GPT in serum are increased on control group compared to normal group but Lycium chinense group and group (which is administrated with the mixed extract of both ectract) decreased apparently the activities of GOT and GPT. The contents of Creatinine, BUN and Glucose in serum has no difference between normal and control group when the Cornus officinalis, Lycium chinense or mixed extract of both extracts were injected. Among them Lycium chinense group showed more normal value compared to Cornus officinalis and the mixture of both extract. The protective effect on rat liver damage caused by carbon tetrachloride is in order of Lycium chinense. The synergistic effects of the mixed extract on liver damage are proved to be better than Lycium chinense or Cornus officinalis singly.

• Journal of Nutrition and Health
• /
• v.47 no.2
• /
• pp.106-112
• /
• 2014

Purpose: This study was conducted in order to investigate the protective effects of ethanolic extract of Acanthopanax koreanum Nakai (AE) against carbon tetrachloride ($CCl_4$)-induced liver injury in rats. Methods: Male Sprague-Dawley rats were randomly divided into four groups in order to receive the following experimental diets with intraperitoneal injection of $CCl_4$ (2.0 mL/kg body weight, 20% solution 0.65 mL) for eight weeks (n = 8 per group): $CCl_4$ control (CON), $CCl_4$ + AE 1% (AE1), $CCl_4$ + AE 3% (AE3), or $CCl_4$ + acanthoic acid 0.037%, which is equivalent to AE 3% (AA). Results: Highest serum ALT activity and albumin level were observed in the $CCL_4$ control group, but showed a significant decrease by either AE or AA supplementation in a dose-dependent manner (p = 0.0063 and 0.0076, respectively). Both hemotoxylin and eosin staining and Masson's staining indicated remarkable prevention of $CCl_4$-induced liver damage in the AE3 group. $TNF{\alpha}$ and IL-6 production were significantly lowered in the AE treated groups, but not in the AA group (p = 0.0016 and p = 0.0002, respectively). The effects of AE3 were greater than those of AA for inflammation and liver toxicity biomarkers. Conclusion: Taken together, the results suggested that ethanolic extract of Acanthopanax koreanum Nakai provided hepatoprotective effects, leading to the reduction of inflammatory response. In addition, the effect of AE was superior to that of single compound AA.

• Korean Journal of Medicinal Crop Science
• /
• v.17 no.3
• /
• pp.217-222
• /
• 2009

The purpose of this study evaluated the immunoregulatory effect of phellinus linteus ethanol (PLE) extracts on liver damage on carbon tetrachloride ($CCl_4$) induced in rats. Four-week old Male Sprague-Dawley rats were divided into the three experimental groups randomly; Control group, $CCl_4$ group, $CCl_4$ + PLE group. We found that effect of PLE on $IFN-\gamma$, STAT1 and pSTAT1 was decrease in vivo. Several genes were demonstrated to be IL-4 inducible prior to the discovery of STAT6. IL-4, STAT6 and pSTAT6 decreased significantly lower in $CCl_4$ + PLE than the $CCl_4$ group. Our data indicated that cytokine protein production were increased in $CCl_4$ group with $CCl_4$ + PLE group. In our data indicate that IgA levels in MLN lymphocytes were low, while IgE was high in $CCl_4$ + PLE group compared with $CCl_4$ group. Therefore, the results of this study show that PLE can be proposed to protect the liver against $CCl_4$-induced immunoregulatory activity in rats.

• The Korea Journal of Herbology
• /
• v.28 no.4
• /
• pp.25-32
• /
• 2013

Objectives : The purpose of this study was to evaluate the hepatoprotective effect of Hovenia dulcis extract on acute and chronic liver injuries induced by alcohol and $CCl_4$ in mice and rats. Methods : In acute alcohol-induced liver injury, mice were administered Hovenia dulcis extracts (60 and 200 mg/kg) orally before and after alcohol administration. In chronic alcohol-induced liver injury, mice were administered alcohol containing liquid diet for 4 weeks. The mice were administered H. dulcis extracts (60 and 200 mg/kg) mixed with the liquid diet. In acute $CCl_4$-induced liver injury, rats received a single dose of $CCl_4$ (2 mL/kg in olive oil, intraperitoneally). Rats were administered H. dulcis extracts (30, 100 and 300 mg/kg) before and after $CCl_4$ administrations. After the ends of the administrations, the serum levels of AST and ALT were measured using chemical analyzer, and ${\gamma}$-GTP levels were measured using spectrophotometer. Results : In acute alcohol-induced liver injury, H. dulcis extracts treated group showed significant reduction in ALT levels compared to those of control group. In chronic alcohol-induced liver injury, it inhibited weight-loss compared to normal group and showed significant reduction in AST, ALT and ${\gamma}$-GTP levels compared to control group. In acute $CCl_4$-induced liver injury, it also showed significant reduction in AST, ALT levels compared to control group. Conclusions : The results show that H. dulcis extract has hepatoprotective effect in acute and chronic alcohol-induced liver injury and acute $CCl_4$-induced liver injury. These findings suggest that H. dulcis could be a potent hepatoprotective agent.

• Archives of Pharmacal Research
• /
• v.16 no.1
• /
• pp.13-17
• /
• 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.

• Archives of Pharmacal Research
• /
• v.23 no.6
• /
• pp.613-619
• /
• 2000

We investigated the expression profiles of rat fibrotic liver induced by bile duct ligation and scission (BDL/S) using the 3'-directed cDNA libraries. The possibility that the 3'-directed cDNA library represents the mRNA population faithfully was examined by northern blots. During the northern analysis based on fibrotic liver expression profile, we found for the first time that purine specific sodium nucleoside cotransporter (SPNT) was upregulated in BDL/S-induced fibrotic liver. To determine whether the accumulation of bile juice could affect the expression of SPNT mRNA or not, we examined the change of SPNT mRNA expression at 3, 14, 28 days after BDL/S operation. No change in SPNT expression was observed in rat liver at 3 days after surgery. In contrast, there were significant increases in SPNT expression at 14 and 28 days after surgery. We also examined whether chronic liver damage affected SPNT mRNA expression. SPNT mRNA level was significantly increased in BDL/S-induced fibrotic rat liver, whereas no significant change was obserbed in fibrotic livers chronically exposed to carbon tetrachloride or dimethylnitrosamine. From the above results, although further study might be needed, it was considered that the increment of SPNT mRNA in BDL/S liver morphological compatibility to human was remarkable.

• Journal of Yeungnam Medical Science
• /
• v.26 no.2
• /
• pp.125-129
• /
• 2009

Colchicine is an alkaloid that has been used for treating acute gouty arthritis, psoriasis, scleroderma and Behcet's syndrome. Colchicine decreased liver fibrosis in rats with carbon tetrachloride induced cirrhosis and in patients with many liver diseases. Therapeutic oral doses of colchicine may cause nausea, vomiting, abdominal pain and diarrhea. The adverse effect of colchicine associated with the dose is bone marrow suppression, and especially neutopenia. Neutropenia has often been reported in patients have taken an overdose of colchicine. We describe a 64-year-old female liver cirrhosis patient with neutropenia that was induced by a therapeutic dose of colchicine.

• Journal of the East Asian Society of Dietary Life
• /
• v.23 no.1
• /
• pp.44-52
• /
• 2013

This study investigated hepatic functional improvement and anti-fibrotic effects of water extracts of black tea. Male Sprague-Dawley rats were divided into four groups (normal, control, and two experimental subgroups: Ba, Bb) and observed for 3 weeks. Liver fibrosis in rats developed from carbon tetrachloride ($CCl_4$) administration, except for the normal group. Except for the normal and control group, the two experimental subgroups were fed water extracts of black tea. The food efficiency ratio significantly increased in the experimental group compared to the control group. The experimental group had a significantly lower liver weight compared to the control group. The ratio of liver weight to body weight was significantly lower in the experimental group than the control group. The levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, blood urea nitrogen, and low-density lipoprotein-cholesterol in serum significantly decreased in the experimental group compared to the control group. The values of hydroxyproline and malondialdehyde in liver were even lower in the experimental group than the control group. In observations on liver histology, weaker inflammation and fibrosis were observed in the experimental group compared to the control group. In conclusion, water extracts of black tea help hepatic cells keep their functions, restraining and protecting the liver from impairments caused by $CCl_4$ administration, and can be effective as anti-fibrotic agents.