• Korean Journal of Fisheries and Aquatic Sciences
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• v.47 no.3
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• pp.204-210
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• 2014

The brown alga Saccharina japonica is consumed as a foodstuff in many countries. Carbon tetrachloride ($CCl_4$) is a potent hepatotoxin that is used to assess hepatotoxicity in animal models. This study assessed the protective effect of S. japonica extract (SJE) on $CCl_4$-induced acute liver injury in rats. Experimental rats were divided into the following three groups: control, $CCl_4$, and $CCl_4$+SJE; the latter two groups were given 150 or 300 mg SJE/kg orally for 10 days. Three hours after the final treatment, all rats-except for those in the control group-were administered intraperitoneal injections of $CCl_4$. One day later, blood and liver samples were collected for evaluation biomarker of levels. Aspartate transaminase (APT; GPT) and alanine aminotransferase (ALT; GOT) levels were markedly lower in the $CCl_4$+SJE group than the $CCl_4$ group. The hepatic superoxide dismutase (SOD) activity of the $CCl_4$+SJE group was significantly lower than that of the $CCl_4$ group. In comparison, glutathione S-transferase (GSH) and catalase (CAT) levels were significantly higher in the $CCl_4$+SJE group. Western blotting revealed that SJE attenuated the $CCl_4$-induced EGFR and MAPK activity in the liver. Thus, we conclude that SJE protects against $CCl_4$-induced hepatotoxicity.

• YAKHAK HOEJI
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• v.56 no.2
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• pp.99-107
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• 2012

The protective effect of AI-1367 (Alnus japonica extract) on liver injury was investigated. Primary rat hepatocyte intoxication was induced by tert-butyl hydroperoxide (tBH), carbon tetrachloride ($CCl_4$), or D-glactosamine (D-GalN). Liver injury was induced by $CCl_4$, D-GalN or MCD (methionine choline deficient)-diet in mouse. The cellular leakage of lactate dehyrogenase and cell viability followed by the treatment of hepatotoxicants were significantly improved by AI-1367 treatment at a concentration range of 5~50 ${\mu}g/ml$ for tBH, 5~50 ${\mu}g/ml$ for D-GalN, and 5~100 ${\mu}g/ml$ for $CCl_4$, respectively. Treatment with AI-1367 (20, 10, 5 mg/kg, p.o.) on liver injury induced by subcutaneous injection of $CCl_4$ or D-GalN reduced significantly the levels of aspartate transaminase and alanine transaminase in serum. Histological observations revealed that fatty acid changes, hepatocyte necrosis and inflammatory cell infiltration in $CCl_4$ (D-GalN)-induced liver injury was improved by administration of AI-1367. AI-1367 treatment (10, 5, 2.5 mg/kg, p.o.) also significantly recovered the body weight change and serum levels of aspartate transaminase, alanine transaminase and triglyceride in liver injury induced by MCD diet. From these results, AI-1367 shows protective effects against tBH, $CCl_4$, D-GalN, or MCD diet-induced hepatotoxicity in vitro or in vivo.

• 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 Physiology & Pathology in Korean Medicine
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• v.22 no.1
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• pp.155-161
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• 2008

Carbon tetrachloride $(CCl_4)-induced$ liver injury depends on a toxic agent that has to be metabolized by the liver NAPDH-cytochrome P450 enzyme system to a highly reactive intermediate. Although several isoforms of cytochrome P450 may metabolize $CC1_4$, attention has been focused largely on the cytochrome P450 2E1 (CYP2E1), which is ethanol-inducible. Alternations in the activity of CYP2E1 affect the susceptibility to hepatic injury from $CC1_4$. In this study, the liver protective effect of the hot water extracts of Scutellaria radix (SR) was investigated. The SR exhibited a hepatoprotective activity against $CCl_4-induced$ liver damage in Chang liver cells. The expression of CYP2E1, measured by RT-PCR and Western blot analysis, was significantly decreased by SR treatment in Chang cells. Based on these findings, it is suggested that hepatoprotective effect of SR possibly related to downregulation of CYP2E1 expression.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.6
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• pp.1415-1423
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• 2007

Carbon tetrachloride ($CCl_4$)-induced liver injury depends on a toxic agent that has to be metabolized by the liver NAPDH-cytochrome P450 enzyme system to a highly reactive intermediate. Alternations in the activity of cytochrome P450 enzymes affect the susceptibility to hepatic injury from $CCl_4$. In this study, we evaluated the potential protective activity of the traditional Korean medicinal herb, Corni fructus (CF), against an experimental model of hepatotoxicity induced by $CCl_4$. The CF exhibited a hepatoprotective activity against $CCl_4-induced$ liver damage in Sprague-Dawley (SD) rats, as measured by GOT, GPT, ALP and histological observation. The CF also showed significant decrease of malodialdehyde (MDA) and increase of glutathion (GSH), catalase activity in rat liver homogenate. In addition, the expression of CYP2E1, as measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis, was significantly decreased in the liver of CF treated SD rats. But $CCl_4$ and CF has no significant effect on 1A1 and 3A1 isoform of cytochrome P450. Based on these findings, it is suggested that hepatoprotective effects of CF possibly related to antioxidative effects and regulation of CYP2E1 expression.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.5
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• pp.1337-1343
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• 2005

The hepato-protective effects of the extract from Protaetia brevitarsis against hepatotoxicity by carbon tetrachloride ($CCI_4$) were studied in rats. The rats were orally treated with $CCI_4$ (50% in corn oil) at initial dose of $1\;m{\ell}/kg$ followed by $0.5m{\ell}/kg$ four times during 2-week period. The extract of P. brevitarsis (50, 100 or 200 mg/kg) or its vehicle was administered day after day from 1 week before $CCI_4$ Injection during five weeks. $CCI_4$ induced hepato-celluar degeneration and necrosis induced to increase in serum aspartate amintransferase (AST) and alanine aminotransferase (ALT) levels. In biochemical analyses, thiobarbituric acid-reactive substances (TBARS) and antioxidant enzymes such as superoxide dismutase (SOD) and catalase in hepatic tissues were remarkably increased by $CCI_4$ treatment. Not only increases in serum AST and ALT, but also induction of lipid peroxidation and antioxidant enzymes in hepatic tissues caused by $CCI_4$ were significantly attenuated by the P. brevitarsis extract in a dose-dependent manner. Such hepato-protective effects of P. brevitarsis extract were confirmed by histopathological examinations, wherein only mild hepatocytic vacuolations were observed in the liver of rats treated with a high dose (100 mg/kg) of P. brevitarsis extract in comparison with severe hepatocytic degenerations administered with $CCI_4$ alone. From these results, it is suggested that the extract of Protaetia brevitarsis could be a promising candidate for the protection of liver injury, based on the preventive effects against morphological cellular injuries, lipid peroxidation and serum biochemical parameters.

• Environmental Analysis Health and Toxicology
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• v.21 no.1 s.52
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• pp.87-92
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• 2006

This study was done to investigate the protective effect of novel 9-amino-1, 2, 3, 4-tetrahydroacridine derivatives on the hepatoprotective effect intoxicated rats induced by carbon tetrachloride ($CCl_4$). A series of currently derivatives of 9-amino-1, 2, 3, 4-tetrahydroacridine have been prepared through the alkly substitution or the ring expansion for the treatment of the Alzheimer's disease. The activities of aminotransferase (aspartate and alanine) and contents of alkaline phosphatase, triglyceride and glutathione S-transferase in 9-amino-1, 2, 3, 4-tetrahydroacridine derivatives pretreated rats were significantly decreased compared to the only carbon tetrachloride treated rats but the contents of cholesterol were increased compared to the only $CCl_4$ treated rats. The result indicated that 9-amino-1, 2, 3, 4-tetrahydroacridine derivatives showed hepatoprotective effect in $CCl_4$ treated rats.

• Korean Journal of Veterinary Research
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• v.32 no.3
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• pp.357-364
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• 1992

Artemisia Iwayomogi Compositae) has been used clinically for jaundice, hepatitis, liver cirrhosis etc. The purposes of present study were to examine pharmacological effects of Artemisia Iwayomogi water extract(AIWE) on biochemical parameters (activities of ALP and LAP, contents of glucose, total bilirubin, total protein and albumin in serum, A/G ratio, and levels of hepatic glycogen) against hepatic injury by carbon tetrachloride($CCl_4$) in rats. The results were as follows ; 1. Increased ALP activities by $CCl_4$ were very significantly(p<0.001) decreased in AIWE posttreatment groups at 72 hours and significantly(p<0.05) decreased in AIWE pretreatment groups at 72 hours. Increased LAP activities by $CCl_4$ were significantly (p<0.05) decreased in AIWE posttreatment groups at 72 hours. A little increased total bilirubin contents by $CCl_4$ were very significantly (p<0.001) decreased in AIWE posttreatment groups at 24, 48 and 72 hours. 2. Increased glucose contents by $CCl_4$ were decreased in AIWE posttreatment groups. Decreased hepatic glycogen levels by $CCl_4$, were significantly (p<0.05) increased in AIWE posttreatment groups at 48 and 72 hours. 3. Decreased total protein contents by $CCl_4$ were significantly (p<0.05) increased in AIWE posttreatment groups at 48, 72 hours. Decreased albumin contents by $CCl_4$ were increased in proportion to numbers of AIWE treatments in AIWE pre- and posttreatement groups. Decreased A/G ratios by $CCl_4$ were significantly (p<0.05) increased in AIWE posttreatment groups at 48 hours. In conclusion, AIWE did not affect normal liver function and had hepatoprotective effects rather than direct preventive effects to $CCl_4$-induced cholestasis, damages in metabolisms of glucose, protein and bilirubin.

• Herbal Formula Science
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• v.31 no.1
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• pp.53-65
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• 2023

Objectives : Present study investigated the hepatoprotective effects and the optimal mixing ratio of fermented Schizandrae Fructus Pomace (fSFP) and Hoveniae Semen Cum Fructus (HSCF) extract combination in carbon tetrachloride (CCl₄)-induced acute liver injury mice. Methods : ICR mice were orally administered with 200 mg/kg of fSFP, HSCF and mixtures of fSFP and HSCF [MSH (w:w); 1:1, 1:2, 1:4, 1:6, 2:1, 4:1, 6:1, and 8:1] for 7 consecutive days. Silymarin (100 mg/kg) was administered as a reference drug. 0.5 mL/kg of CCl₄ was injected intraperitoneally to induce acute liver injury. Body weight gain, relative liver weight, serum chemistry, histopathological analysis, and hepatic endogenous antioxidants capacities were observed. Results : All diverse combinations of MSH significantly reduced relative liver weight increase by CCl₄. In addition, MSH administrations significantly decreased the elevation of serum alanine aminotransferase and aspartate aminotransferase activities by CCl₄. Histopathological observation indicated that all MSH treatments significantly reduced the increase of degenerated hepatocytes, inflammatory cell infiltration, and histological activity index score by CCl₄. Moreover, all MSH administrations reduced the elevation of malondialdehyde contents, and ameliorated the reduction of hepatic glutathione contents, superoxide dismutase activity, and catalase activity. Among the various mixing ratio of MSH combinations, MSH 1:1 and 2:1 showed the most potent anti-oxidative stress, and hepatoprotective effect. Conclusion : Present results suggest that 1:1 and 2:1 combinations of MSH is promising herbal formulation with the hepatoprotective effect against oxidative stress.

• Korean Journal of Pharmacognosy
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• v.36 no.1 s.140
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• pp.44-49
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• 2005

The protective effects of the DWP-04 [DDB : selenium yeast: glutathione {31.1 : 6.8 : 62.1 (%, w/w)} against hepatotoxicity by carbon tetrachloride $(CCl_4)$ were studied in rats. The rats were intraperitoneally injected with $CCl_4$ (50% in com oil) at initial dose of 1 ml/kg followed by 0.5 ml/kg 3 times during 1 week. The DWP-04 (50, 100 or 200 mg/kg) or its vehicle was administered everyday before the start of $CCl_4$ injection for two weeks. $CCl_4$ induced hepatocelluar degeneration and necrosis, which led to a great increase in serum aminotransferase, alkaline phosphatase activity and serum lipid levels. It was found by biochemical analysis that $CCl_4$ treatment remarkably increased thiobarbituric acid reactive substances and physphatidylcholine hydroperoxide in hepatic tissues and induced antioxidant enzymes such as catalase and superoxide dismutase (SOD). Liver and serum lipids were significantly lower in rats fed on DWP-04 than in rats induced by $CCl_4$ only-treatment. These results suggested that the DWP-04 could be a promising candidate for the protection of liver injury based on the preventive effects against lipid peroxidation and serum biochemical parameters.