• Journal of Environmental Health Sciences
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• v.29 no.2
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• pp.80-86
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• 2003

To evaluate the effect of cyclohexane(CH) treatment on the serum levels of glutathion S-transferase(GST) activity in liver damaged animals, damaged liver was induced with pretreatment of 50% $CCl_4$ dissolved in olive oil (0.1 m1/100g body weight) intraperitoneally 17 times every other day. To $CCl_4$-treated rats, CH (1.56 g/kg body weight, i.p) was injected once and then the animals were sacrificed at 4 hours after injection of CH. The $CCl_4$-treated animals were identified as severe liver damage on the basis of liver functional findings, 1,e, increased serum levels of alanine aminotransferase(ALT), alkaline phosphate(ALP) and xanthine oxidase(XO) activities. On the other hand, $CCl_4$-treated animals injected with CH once($CCl_4$-pretreated animals) showed more decreased serum levels of ALT and XO, and more increased those of ALP rather than $CCl_4$-treated animals. In case of comparing the GST with ALT activity in liver, both $CCl_4$-treated and pretreated animals showed similar changing pattern of enzyme actvity. Especially $CCl_4$-pretreated animals showed significantly increased serum level of GST actvity compared with the $CCl_4$-treated those, whereas those of ALT showed reversed tendency. In aspects of GST enzyme kinetics, $CCl_4$-pretreated animals showed higher Vmax of liver GST enzyme than $CCl_4$-treated animals. In conclusion, injection of CH to the liver damaged rats led to enhanced liver damage and more increased activity of serum GST which may be chiefly caused by the enzyme induction.

• Korean Journal of Pharmacognosy
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• v.25 no.4 s.99
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• pp.388-394
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• 1994

80% Methanol extracts of 44 traditional drugs used for the treatment of liver diseases or tonic effects were screened for anti-hepatotoxic activity by in vitro assay using $CCl_4-induced$ cytotoxicity in primary cultured rat hepatocytes. $CCl_4-induced$ cytotoxicity was evaluated by determination of LDH, GOT or GPT activity in the medium. Rehmaniae Radix Preparata and Gelantina nigra inhibited the release of LDH, GOT or GPT from $CCl_4-treated$ hepatocytes. Gibotii Rhizoma and Eucommiae Cortex showed inhibitory effect on release of LDH from normal hepatocytes as well as $CCl_4-treated$ hepatocytes. Eucommiae Cortex and Lili Bulbus decreased release of GOT and LDH from normal hepatocytes, respectively. Astragali Radix inhibited release of GPT in $CCl_4-treated$ hepatocytes. Phlomidis Radix, Imperatae Rhizoma, Cistanchis Herba, Broussonetiae Fructus, Asparagi Tuber, Trigonellae Semen and Polgonati Rhizoma inhibited release of LDH from $CCl_4-treated$ hepatocytes. Among 44 traditional drugs, most of them released LDH, GOT or GPT at the dose of 1 mg/ml in normal hepatocytes, and Drynariae Rhizoma, Acanthopanacis Cortex, Longanae Arillus, Atratylodis Rhizoma and Ecliptae Herba increased $CCl_4-induced$ cytotoxicity.

• Biomedical Science Letters
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• v.8 no.1
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• pp.47-52
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• 2002

To investigate an effect of cyclohexanone (CHO) treatment on the serum levels of xanthine oxidase (XO) in liver damaged animals, the rats were intraperitoneally pretreated with 50% carbon tetrachloride ($CCl_4$) in olive oil (0.1 mL/ 100 g body weight) 14 times every other day. To the $CCl_4$-pretreated rats, CHO (1.56 g/kg body weight) was injected once and then the animals were sacrificed at 4 hours after CHO treatment. The increasing rate of serum and liver XO activities to the control was higher in CHO-treated animals pretreated with $CCl_4$ than the $CCl_4$-pretreated those. Concomitantly CHO injection to the $CCl_4$-pretreated animals showed somewhat higher Vmax and lower Km value in the kinetics of liver XO enzyme. Furthermore, increasing rate of hepatic malonedialdehyde content to the control was also higher in CHO-treated animals pretreated with $CCl_4$ than $CCl_4$-pretreated those. On the other hand, the injection of CHO to the $CCl_4$-pretreated animals showed the more enhanced liver damage on the basis of liver function finding; liver weight per body weight (%), serum levels of alanine aminotransferase activity and hepatic glucose-6-phosphatase activity. In conclusion, injection of CHO to the $CCl_4$-pretreated rats led to more increased activity of serum XO and it may be caused by acceleration of hepatocyte membrane permeability and induction of enzyme protein.

• Korean Journal of Pharmacognosy
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• v.26 no.1
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• pp.51-56
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• 1995

To devise an in vitro screening method for antihepatotoxic activity, $CCl_4-induced$ cytotoxicities in primary cultures rat hepatocytes were examined. When rat hepatocytes were intoxicated with 0.5, 1.0 or 1.5 mM $CCl_4$ for 1.5, 3 or 19hr, in order of LDH>GOT>GPT release form hepatocytes was increased in a dose-dependent manner. Treatment with 1.5 mM $CCl_4$ for 1.5 hr showed maximum increase in activity of LDH, GOT or GPT released in the medium compared with the control. At this experimental condition, well known antihepatotoxic substances, glycyrrhizin and silybin markedly inhibited $CCl_4-induced$ cytotoxicities. These results demonstrated that the screening method using $CCl_4-induced$ injury in primary cultured rat hepatocytes might be suitable in vitro assay for antihepatotoxic activity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.20 no.6
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• pp.527-537
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• 1991

To evaluate an effect of liver xanthine oxidase on the induction of liver damage, carbon tetrachloride (CCl4) was intraperitoneally injected twice at 0.1ml/100g body weight to the rate fed a low (LP)or high protein diet(HP) while the control group fed LP or HP received only olive oil. The changing rate of liver xanthine oxidas activity was compared with that of a free radical generating enzyme, liver aniline hydroxylase and a scavenging enzyme, glutathions S-transferase activity between the rate fed a LP and those fed HP, and the two groups treated with CCl4. Concomitantly, the degree of liver damage which could be considered as the paramete for CCl4 metabolism in case of CCl4-intoxicated animal was observed in the present experimental conditions and the effect of allopurinol, xanthine oxidase inhibitor, on the CCl4-toxicity of rate liver was alos demostrated. On the other hand, the comparative effect of actinomycin D on the liver and serum xanthine oxidase of CCl4-treated rats fed HP with that of those fed LP and the kinetics of purifed liver enzyme from the liver of CCl4-treated rats fed HP was also compared with that of those fed LP to clarify the differences of xanthine oxidase activity between two groups. The increasing rate of liver weigth/body wt, serum levels of ALT and the decreasing rate of hepatic ALT activity and protein contents to each control group were higher in CCl4-treated rats fed HP than those fed LP. Under the animal models as indentified by the present data herein, the liver xanthine oxidase activity was higher in CCl4-treated rats fed HP than those fed LP, and the control group fed HP also showed the much higher activity xanthine oxidase than that fed LP, whereas there were no differences in the activity of hepatic aniline hydroxylase and glutathions S-transferase between the two group treated with CCl4. Although the hepatic aniline hydroxylase activity was somewhat higher in the rats fed HP than those fed LP, the increasing rate of liver xanthine oxidase to the rats fed LP was higher in those fed HP than that of liver aniline hydroxylase. The degree of liver damage identified such as liver weight and serum ALT activity was less in the CCl4-treated rats pretreated with allopurinol. These results suggest that even a system at which xanthine oxidase acts as well as the drug metabolizing enzyme may influence the acelatin of CCl4 metabolism. In addition, the purified liver xanthine oxidase from CCl4-treated rats fed HP showed decreased Km value when compared to its control group. The Km value of liver xanthine oxidase of CCl4-treated rats fed LP showed a similar Km value with its control group. Furthermore, the decreasing rate of liver and serum xanthine oxidase acitivity in CCl4-treated rats pretreated with actinomycin D to the CCl4-treated rats was higher in rats fed HP than in those fed LP. These results suggest that the inductino of xanthine oxidase in CCl4-treated rats fed HP may be greater than in those fed LP.

• 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.

• 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.

• Journal of Pharmacopuncture
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• v.2 no.1 s.2
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• pp.111-133
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• 1999

These studies were carried out to investigate the effect of Herbal-acupuncture with Inzinsammultang extract on the recovery from liver injury of rats. The liver injury of rats induced with 0.3ml/ea carbon tetrachloride. The Herbal-acupunture with Inzinsam multang extract solution inserted into corresponding focus of Kansu(BL18) in rats. In this study, SD-Rats(Sprague-Dawley) were divided into 4 groups ; Normal group (None treated group), Control-group(The group not treated after $CCI_4$-intoxication), Treated group; Example I-group(Saline-injected groups after $CCl_4$-intoxication) and Example II-group(Inzinsammultang-injected groups after $CCl_4$-intoxication). Through histological observation, Example II-group sho-ws that liver injury is weaker than Control group.(p<0.05) Biochemical assays for each serum enzyme activities of AST, ALT and LDH, levels of albumin, ${\gamma}$-GT, TG, total cholesterol were performed. The results were summarized as follows 1. AST(Aspartate aminotransferase) activity in serum significantly decreased in the Inzinsammultang-injected groups after $CCl_4$-intoxication. Inzinsammultang-injected groups after $CCl_4$-intoxication showed significantly higher AST activities, compared with the Saline-injected groups after $CCl_4$-intoxication.(p<0.05) 2. ALT(Alanine aminotransferase) activity in serum significantly decreased in the Inzinsammultang-injected groups after $CCl_4$-intoxication. The Inzinsammultang-injected groups after $CCl_4$-intoxication showed significantly higher AST activities, compared with the Saline-injected groups after $CCl_4$-intoxication(p<0.05) 3. Level of Albumin in serum significantly increased in the Inzinsarnmultang-injected groups after $CCl_4$-intoxication. 4. LDH(Lactate dehydrogenase) activities in serum significantly decreased in the Inzinsammultang-injected groups after $CCl_4$-intoxication.(p<0.05) 5. ${\gamma}$-GT(Glutamyl transferase) in serum significantly decreased in the Inzinsammultang-injected groups after $CCl_4$-intoxication(p<0.05) 6. As for the TG(Triglyceride) levels in serum, Inzinsammultang-injected groups after $CCl_4$-intoxication is no significant differences compared with the Saline-injected groups after $CCl_4$-intoxication.(p<0.05) 7. Total cholesterol in serum significantly increased in the Inzinsarnmultang-injected groups after $CCl_4$-intoxication.(p<0.05) Those results indicate that the Inzinsammultang Herbal-acupuncture have significant effects on the liver injury induced by $CCl_4$. So it is expected that the Inzinsammultang Herbal-acupuncture can be used to cure inflammations and recover the functions of damaged liver cells.

• Journal of Veterinary Clinics
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• v.14 no.2
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• pp.273-278
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• 1997

Several serum enzyme activities were measured after intraBeritoneal administration of 0.01 ml $CCl_{4}$ per 100 g of body weight in Sprague Dawley rats. Senun AST activity increased significantly after administration of CCl$_{4}$ (P<0.05). The serum AST activity at 2 hours after $CCl_{4} administration (475 {\pm} 10^{6} IU/L)$ was significantly higher than that of control group $(65 {\pm} 14 IU/L)$. The high level of serum AST activity maintained up to 48 hours. Serum ALT activity in $CCl_{4}$-treated groups was also significantly higher from 4 hours after treatment companied to control group and the high level maintained up to 48 hours. Serum ALP and ${\gamma} GTP activities in CCl_{4}$-treated groups were significantly higher from 8 hours after treatment compared to control group and the level maintained up to 48 hours.

• YAKHAK HOEJI
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• v.33 no.2
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• pp.101-110
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• 1989

These studies were attempted to investigate the therapeutic effect earthworm (Lamnodrilus gotai Hatai) extract (LS) on the liver damage induced by carbon tetrachloride ($CCl_4$) in rats. Male rats (Sprague-Dawley) were treated with sub-chronic concentration of $CCl_4$, which was 0.2 ml/kg of $CCl_4$ via peroral administration twice a week. LS administration to rats (6 ml/kg,po) prevented the development of fatty liver, necrosis and fibrosis induced by $CCl_4$. Furthermore, as compared with rats suspended after treated with $CCl_4$ only, LS treatment significantly decreased the increment in serum enzyme activities, liver enlargement and improved growth rate. This protective effect was observed when LS was given monthly for 4 months after $CCl_4$ treated for 2 months. These results suggest that earthworm extract has appreciable therapeutic effect on $CCl_4$-induced hepatotoxicity.