• 대한약리학회지
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• 제16권2호
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• pp.31-38
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• 1980

Calvert et al. formulated the hypothesis that carbon tetrachloride ($CCl_4$) acted on the central nervous system to produce and intensify sympathetic discharge which resulted in anoxic necrosis of the liver. Recknagel suggested that the essential feature of $CCl_4$ hepatotoxicity depended on the cleavage of it to $CCl_3$(free radical) and the peroxidative decomposition of cytoplasmic membrane structural lipids. And there are many reports which show the increase of adrenergic activity in hyperthyroidism. In this paper, the influence of thyroxine on the hepatotexicity of carbon tetrachloride was investigated in mice. The results obtained were summarized as follows; 1) Hepatic total lipid and lipid peroxide contents were slightly decreased by L-sodium thyroxine injection(4mg/kg/day for 4days or 6days), but hepatic glycogen content was significantly decreased. 2) Hepatic total lipid and lipid peroxide contents and serum lactic dehydrogenase activity were significantly increased by $CCl_4$ (4 ml/kg single dose or triple dose: 4ml/kg/day for 3days), but hepatic glycogen content was significantly decreased. 3) The increase of hepatic total lipid and lipid peroxide contents and serum lactic dehydrogenase activity induced by $CCl_4$ were significantly inhitited by the pretreatment of thyroxine. 4) The decrease of hepatic glycogen induced by $CCl_4$ was not affected by the pretreatment of thyroxine.

• 약학회지
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• 제43권6호
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• pp.827-833
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• 1999

In this study, we have investigated the effect of Biphenyl Dimethyl Dicarboxylate (DDB), a synthetic analogue of Schizandrin C isolated from Schizandrae Fructus on cytochrome $P_450$ lAl and 2Bl, and the protective mechanism against $CCl_4-induced$ hepatotoxicity in rat liver. After DDB was administered into male rats for different periods of time (1~7 days) and with different doses (25, 50, 100 and 200 mg/kg), mRNA levels of CYPlAl were measured by polymearse chain reaction (PCR) and assayed the activities of CYPlAl specific ethoxyresorufin-O-dealkylase (EROD) and CYP2Bl specific benzyloxyresorufin-O-dealkylase (BROD). DDB treatment resulted in increase in CYP2Bl mRNA level and BROD activity, whereas there was no change in CYPlAl mRNA level and EROD activity. This effect of DDB was time-and dose-dependent and reached maximal level by 3 day and 200 mg/kg treatment. In addition, rats were pre-treated with DDB at doses of 25, 50 or 100 mg/kg daily for 4 days, 3-hr after final treatment on the 4th day, $CCl_4$ 0.3ml/kg was intraperitonially injected into the rats to examine the effect of DDB on $CCl_4-induced$ hepatic injury. Serum levels of ALT and AST were determined and histopathological examination was done in rat liver. Furthermore, we have measured hepatic microsomal malondialdehyde(MDA) level, a parameter of lipid peroxidation. Based on serum ALT level and lipid peroxidation, pretreatment of DDB, 50 mg/kg appeared the most protective effect against $CCl_4-induced$ heapatotoxity. These results indicate that DDB stimulates CYP2Bl mRNA level and BROD activity in time and dose dependent manner and suggest that protective effect of DDB on $CCl_4-induced$ hepatotoxicity may be mediated through free radical scavenging.

• 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.

• Toxicological Research
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• 제25권2호
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• pp.71-78
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• 2009

We investigated the pathogenesis of liver tissue damage during the lipid peroxidation and fibrogenesis with the observation of correlations between the parameters of collagen synthesis (and deposition) and lipid peroxidation in liver fibrosis (cirrhosis) rats. Rats were randomly divided into two groups, normal and $CCl_4$-thiopental sod. intoxicated group. And the one group was treated intragastrically with the mixture of $CCl_4$-thiopental sod. 3 times per week for 3 weeks. The liver tissue and sera were used for the measurement of hydroxyproline (HYP), malonedialdehyde (MDA) and superoxide dismutase (SOD). Biochemical parameters such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total-bilirubin and blood urea nitrogen (BUN) were measured. Additionally, the expression of collagen ${\alpha}1$(III) and $\beta$-actin mRNA was observed by RTPCR. The histological change in liver tissue was also observed by Masson's trichrome and H&E staining. Correlation analysis was carried by Spearman's rho method. All biochemical parameters except total-bilirubin were significantly higher in the $CCl_4$-thiopental sod. treated group than that of the normal group (p < 0.01). In the $CCl_4$-thiopental sod. treated group, Hyp as a parameter of collagen synthesis (deposition) and MDA as a metabolite of lipid peroxidation, were significantly elevated by 1.98 and 2.11 times higher than that of the normal group (p < 0.001) respectively. The activity of SOD in the $CCl_4$-thiopental sod. treated group is decreased significantly by 44.8% (p < 0.001). And collagen ${\alpha}1$(III) mRNA was more expressed in the $CCl_4$-thiopental sod. treated group than that of the normal group. However, the expression of $\beta$-actin mRNA is showed similar in both of groups. A good correlation was observed between the content of hyp and MDA concentration (r = 0.70, n = 40) in the two groups. And the correlation between the levels of hyp and SOD (r = -0.71, n = 25) is also reliable. However, no correlation were observed between MDA concentration and SOD (r = -0.40, n = 25) in the two groups. Elevated levels of MDA in $CCl_4$-thiopental sod. treated rats indicated enhancement of lipid peroxidation, which is accompanied by a decrease in SOD activity. Moreover, we could confirm that the parameters of collagen synthesis (and deposition) is in good correlation with the metabolite of lipid peroxidation (MDA) and the lipid peroxidation antagonizing enzyme (SOD). Hence, we propose that (1) lipid peroxidation and collagen synthesis (and deposition) could be enhanced by intragastrically application of $CCl_4$-thiopental sod. during a short terms. And (2) the intoxication of $CCl_4$-thiopental sod. could be used for monitoring of lipid peroxidation and collagen synthesis (and deposition) for test of antioxidant and antifibrotic agent.

• 한국응용과학기술학회지
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• 제34권3호
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• pp.443-450
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• 2017

Dawley 계 숫컷 흰쥐(200~210g)를 정상군, $CCl_4$-대조군, $CCl_4$-실험군으로 나누어 실험군은 갈근 에탄올 추출물을 1,000mg/kg,b.w의 용량으로 1일1회7일간 경구 투여 후 사염화탄소를 0.6mg/kg,b.w의 용량으로 복강내 주사 후 다음날 개복하여 혈청내의 Alanine aminotransferase(ALT), Aspartate aminotransferase(AST), Alkaline phosphatase(ALP), Glutamyltranspeptidase(${\gamma}$-GT), Lactate dehydro-genase(LDH)의 활성도와 중성지방, 콜레스테롤 함량을 측정한 결과 갈근 추출물 투여군에서 $CCl_4$-대조군과 비교하여 유의적인 감소(p<0.05)를 나타내었으며, HDL-콜레스테롤은 유의적인 증가(P0.05)를 나타내었다. 간조직중의 지질과산화 함량과 Catalase(CAT), Glutathione peroxiddase(GSH-Px)의 항산화 효소 활성은 유의적인 감소를 나타내었다. 반면에 간 조직중의 glutathione 함량은 유의적인 증가를 나타내었다. 이 실험 결과 갈근 에탄올 추출물은 사염화탄소 투여에 의한 간 손상을 억제하는 보호물질과 항산화 물질을 함유하고 있음을 알 수 있었다.

• 대한약리학회지
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• 제32권1호
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• pp.75-82
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• 1996

사염화 탄소에 의한 과산화 지질 증가 및 간 손상에 calcium 및 Kupffer cell의 역할 및 calcium channel blocker의 간 손상에 대한 방어 효과를 연구하였다. 사염화 탄소는 (1 gm/kg, ig) 간의 malondialdehyde (nmole/gm liver) 및 혈중 AST와 ALT (lU/ml) 활성도의 현저한 증가를 나타내었다. 고 농도의 Retinol (250,000U/kg/day)로 인한 Kupffer cell의 활성 증가는 사염화 탄소에 의한 간 과산화 지질 증가 및 간 손상에 상승 작용을 나타낸 반면, $GdCl_3$ 전처리는 $CCl_4$로 인한 ALT의 증가를 감소시켰다. 한편 Retinol 처치군에 Diltiazem (10mg/kg/day)을 병행하여 처치한 결과, 사염화 탄소에 의한 혈중 AST 및 ALT의 증가를 Retinol 단독 처치군에 비하여 현저하게 억제시킬 수 있었다. 이 결과들이 Retinol 혹은 Diltiazem의 투여에 의한 사염화 탄소가 cytochrome P450에 의한 대사 활성 또는 GSH와 관련된 항산화 기전에 미치는 영향에 기인한 것인가를 규명하기 위하여 cytochrome P450, cytochrome P4502El 활성도, GSH reductase 및 GSH peroxidase 활성도를 측정하였다. 그 결과, Retinol 및 Diltiazem의 전처리는 이들 효소의 활성도에 미치는 영향은 대조군에 비하여 유의한 차이가 없었다. 이상의 실험 결과를 종합하여 보면, 사염화 탄소의 투여에 의한 간 손상은 세포내 calcium의 증가를 가져오며, 이는 이차적으로 Kupffer cell을 활성화 시켜 이미 손상된 간세포의 독성을 증가시켰으며, calcium channel blocker인 Diltiazem의 투여는 사염화 탄소의 간독성을 현저하게 감소시키는 효과를 나타내었다.

• Archives of Pharmacal Research
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• 제18권4호
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• pp.289-292
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• 1995

Icariside II, a flavonol glycoside, was isolated from the aerial part of Epimedium Koreanum Nakai by the anti-hepatotoxic acitivity guided fractionation technique employing $CCl_4-in-toxicated$ primary cultured rat hepatocytes as an assay system. Its anti-hepatotoxic activity was evaluated by measuring activity of glutamic pyruvic transaminase released from the $CCl_4-in-toxicated$ primary cultured rat hapatocytes. Icariside II significantly reduced the activity of glutamic pyruvic transaminase released from the $CCl_4-in-toxicated$ primary cultured rat hepatocytes and resulted in 78% recovery of the toxicity at the concentration of $200{\;}\mu\textrm{m}$. The anti-hepatotoxic activity of icariside II on the $CCl_4-in-toxicated$ primary cultured rat hepatocytes was as potent as that of silybin.

• Biomolecules & Therapeutics
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• 제8권4호
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• pp.293-298
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• 2000

Bergenin is a C-glucoside of 4-O-methyl gallic acid that has been isolated from the cortex of Mallotus japonicus (Euphorbiaceae). Acetylbergenin was synthesized by acetylation from bergenin to increase lipophilic and physiological activities. The therapeutic effects of bergenin and acetylbergenin were evaluated against carbon tetrachloride ($CCl_4$)-induced hepatotoxicity in rats. Bergenin and acetylbergenin were administered orally once daily for successive 5 days, after the intraperitoneal injection of a mixture 0.5 m1/kg of $CCl_4$ in olive oil (1:1). The substantially elevated serum enzymatic activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and ${\gamma}$-glutamyltransferase induced by $CCl_4$ were restored towards normalization by posttreatment with bergenin and acetylbergenin. Bergenin and acetylbergenin also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of glutathione content induced by $CCl_4$ in a dose dependent fashion. In addition, the decreased activities of glutathione S-transferase and glutathione reductase were restored towards normalization. These results suggest that therapeutic effects of bergenin and acetylbergenin may be related complex mechanisms that involve prevention of lipid peroxidation and preservation of hepatic GSH. The results of this study clearly indicate that bergenin and acetylbergenin have potent hepatothrapeutic action against $CCl_4$-induced hepatotoxicity in rats. In addition, acetylbergenin 50 mgHg showed almost the same levels of hepatoprotective activity as those of bergenin 100 mgAg, indicating the fact that lipophilic acetylbergenin is more effective in the hepatoprotective action against $CCl_4$ than bergenin.

• 대한수의학회지
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• 제34권3호
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• pp.619-626
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• 1994

The purpose of present study was to examine pharmacological effect of Artemisia Iwayomogi methanol extract(AIME) on biochemical parameters(activities of AST, ALT, LDH, and ALP, contents of total bilirubin, total protein, albumin and A/G ratio in serum and levels of hepatic microsomal lipid peroxide and glucose-6-phosphatase activities) against hepatic injury by carbon tetrachloride($CCl_4$) in rats. Increased AST, ALT and LDH activities by $CCl_4$ were decreased in AIMS treatment group at 48 or 72 hours. Together, increased ALP activity by $CCl_4$ almost returned toward normal value in AIME treatment group at 72 hours. Serum total bilirubin contents increased to 87, 79 and 31% compared with normal group by $CCl_4$ which were decreased to 64, 42 and 26% in AIME treatment group at 24, 48 and 72 hours, respectively. Decreased contents of total protein and albumin, and A/G ratio by $CCl_4$ were recovered in AIME treatment group. Hepatic microsomal lipid peroxide levels(nmol malonic dialdehyde/100mg protein) increased to 140, 95 and 78% compared with normal group by $CCl_4$ which were decreased to 107, 74 and 65% in AIME treatment group at 24, 48 and 72 hours, separately. Hepatic microsomal glucose-6-phosphatase activities decreased to 60, 50 and 53% compared with normal group by $CCl_4$ at 24, 48 and 72 hours, respectively, which were increased at 72 hours in AIME treatment group. In conclusion, AIME enhanced the amelioration process from $CCl_4$-induced lipid peroxidation, degeneration of liver cell, and impairment of protein and bilirubin metabolisms.

• 대한한방내과학회지
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• 제16권2호
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• pp.1-8
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• 1995

Effects of sosihotangganogyong on the activity of serum transferase and hepatic lipid peroxide in mice with $CCl_4$ solution were determined. The activity of ALT showed a high value in the mice with $CCl_4$, however in the mice with sosihotang and sosihotangganogyong, these values showed a tendency to rapid recovery compared with those of the mice with $CCl_4$ only and the activity of ALT in the group of sosihotang and sosihotangganogyong showed a low values compared with $CCl_4$ only group on the 21 days after treatment. On the 21 days after treatment, the activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and lactic dehydrogenase (LDH) in the mice with sosihotang and sosihotangganogyog were similar to those of control group, however these values of $CCl_4$ only group showed a high values compared with those of other groups. The value of hepatic lipid peroxide in the mice with sosihotang and sosihotangganogyong showed a tendency to rapid decrease and recovery compared with those of $CCl_4$ only group and on the 21 days after treatment, this value showed a similar to those of control group. The activity of serum transferase and the value of hepatic lipid peroxide in the mice with sosihotngganogyong showed a tendency to decrease compared with those of sosihotang group, however these values showed a no significantly deference. Results from this study indicated that the sosihotagganogyong can effectively improve the recovery of liver function in mice with $CCl_4$.