• 한국수산과학회지
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• 제47권3호
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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.

• IMMUNE NETWORK
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• 제5권4호
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• pp.237-246
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• 2005

Background: Little information is available on the identification and characterization of the upstream regulators of the signal transduction cascades for Mycobacterium tuberculosis (M. tbc)-induced ERK 1/2 activation and chemokine expression. We investigated the signaling mechanisms involved in expression of CCL3 /MIP-1 and CCL4/MIP-1 in human primary monocytes infected with M. tbc. Methods: MAP kinase phosphorylation was determined using western blot analysis with specific primary antibodies (ERK 1/2, and phospho-ERK1/2), and the upstream signaling pathways were further investigated using specific inhibitors. Results: An avirulent strain, M. tbc H37Ra, induced greater and more sustained ERK 1/2 phosphorylation, and higher CCL3 and CCL4 production, than did M. tbc H37Rv. Specific inhibitors for mitogen-activated protein kinase (MAPK) kinase (MEK; U0126 and PD98059) significantly inhibited the expression of CCL3 and CCL4 in human monocytes. Mycobactetia-mediated expression of CCL3 and CCL4 was not inhibited by the Ras inhibitor manumycin A or the Raf-1 inhibitor GW 5074. On the other hand, phospholipase C (PLC) inhibitor (U73122) and protein kinase C (PKC)specific inhibitors ($G\ddot{o}6976$ and Ro31-8220) significantly reduced M. tbc-induced activation of ERK 1/2 and chemokine synthesis. Conclusion: These results are the first to demonstrate that the PLC-PKC-MEK-ERK, not the Ras-Raf-MEK-ERK, pathway is the major signaling pathway inducing M. tbc-mediated CCL3 and CCL4 expression in human primary monocytes.

• Biomolecules & Therapeutics
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• 제19권3호
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• pp.302-307
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• 2011

Peptidoglycan (PGN) is detected in inflammatory cell-rich regions of human atheromatous plaques. The present study investigated the effects of PGN on CC chemokine ligand 3 (CCL3) expression, which is elevated in the atherosclerotic arteries, and determined cellular factors involved in PGN-mediated CCL3 up-regulation in mononuclear cells, with the goal of understanding the molecular mechanisms of inflammatory responses to bacterial pathogen-associated molecular patterns in diseased arteries. Exposure of human monocytic leukemia THP-1 cells to PGN resulted in enhanced secretion of CCL3 and profound induction of the CCL3 gene transcript. Both events were abrogated by oxidized 1-palmitoyl-2-arachidonosyl-sn-phosphatidylcholine, an inhibitor of Toll-like receptors 2/4. Pharmacological inhibitors such as U0126, SP6001250, Akt inhibitor IV, rapamycin, RO318220, diphenyleneiodonium chloride, and N-acetylcysteine also significantly attenuated PGN-mediated CCL3 up-regulation. However, polymyxin B, LY294002, and SB202190 did not influence CCL3 expression. We propose that PGN contributes to enhanced CCL3 expression in atherosclerotic plaques and that Toll-like receptors (TLR2), Akt, mTOR, mitogen-activated protein kinase, and reactive oxygen species are involved in that process.

• 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.

• 한국식품영양과학회지
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• 제22권6호
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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.

• 대한약침학회지
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• 제2권1호
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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.

• 한국임상수의학회지
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• 제20권4호
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• pp.443-448
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• 2003

본 연구는 전십자인대가 단열된 개의 슬관절액에서 tartrate-resistant acid phosphatase (TRAP) 와 cathepsin K의 변화를 알아봄으로서 십자인대에 관련된 질병 또는 십자인대 치료 실패에 따른 퇴행성관절염의의 조기 진단 및 치료에 관한 정보를 얻기 위하여 실시하였다. 실험동물로는 전방십자인대가 단열된 30두의 개와 정상 성견 8 두 그리고 어린 정상 개 9두를 사용하였다. 슬관절액 내의 TRAP 과 Cathepsin K의 변화를 확인하기 위하여 조직화학 염색과 면역조직화학염색을 실시하였다. 조직학적인 검사 결과 정상견에서는 TRAP과 Cathepsin K 세포들은 찾아보기 힘들었으나 전방십자인대가 단열된 개에 있어서는 TRAP 과 Cathepsin K 그리고 chondroid metaplasia가 중심부분에서 증가되고 있음을 관찰하였다. 이러한 결과로 보아 TRAP과 Cathepsin K 세포들은 전방십자인대가 단열 또는 단열 후 회복되는 과정에서 상호 보조적으로 관여하며 세포외 방출과 관계가 있는 것으로 생각된다.

• Korean Journal of Acupuncture
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• 제25권2호
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• pp.211-224
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• 2008

Objectives : To investigate the effect of electro-acupuncture (EA) at GB34 on hepatotoxicity in $CCl_4$-intoxicated rats. Methods : Rats were injected with $CCl_4$ and treated with acupuncture or 2 Hz electro-acupuncture (EA) at left GB34 three times a week for 10 weeks. A non-acupoint in left gluteal area was selected as a sham point. To estimate the effects of EA on hepatotoxicity in rats, body weight, liver weight and liver index were measured, and biochemical assays for serum ALT, AST, ALP and total cholesterol, and hematological analysis for RBC, WBC, PLT, hemoglobin, lymphocytes, neutrophils and monocytes, and histology analysis of liver tissue were performed. Results : 1. Lymphocyte level in blood was significantly decreased by $CCl_4$-intoxication and significantly increased by acupuncture and 2 Hz EA at left GB34. 2. Neutrophill and monocyte level in blood was increased by $CCl_4$-intoxication and significantly reduced by acupuncture and 2 Hz EA at left GB34. 3. Acupuncture and 2 Hz EA at left GB34 significantly reduced serum ALT and AST which were increased by $CCl_4$-intoxication. 4. EA at GB34 significantly reduced serum ALT and AST as compared with EA at sham point in $CCl_4$-intoxicated rat. 5. No significant difference was found between the effects of acupuncture and that of 2 Hz EA on $CCl_4$-induced liver damage in rats. Conclusions : 2 Hz EA at GB34 has hepatoprotective effects on $CCl_4$-induced liver damage in rats and the point-specificity of GB34 may be involved in these effects.

• Nutritional Sciences
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• 제8권4호
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• pp.212-218
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• 2005

Hepatoprotective effects of the extract of Kochiae fructus (KF), a traditional oriental medicinal plant, were evaluated against carbon tetrachloride($CCl_4$)-induced liver damage in rats. Male Sprague-Dawley rats were divided into control, $CCl_4,\;CCl_4$ plus methanol extract of KF (KFM-$CCl_4$), and $CCl_4$ plus butanol extract of KF (KFB-$CCl_4$) groups. KFM and KFB were orally administered once a day (200 mg/kg body weight) for 14 days. A mixture of 0.2 mL/100 g body weight of $CCl_4$ in olive oil was injected at 30 minutes after the final administration of KFM and KFB. The KFB pretreatment resulted in a significant decrease in the serum transaminase and lactic dehydrogenase levels in the $CCl_4$-treated rats. The $CCl_4$ treatment significantly lowered the activities of glutathione, glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px). However, pretreatment with KFM and KFB resulted in a significant increase in the glutathione, GR and GST levels. KFB increased the activities of SOD, catalase and GSH-Px, but KFM did not alter them. Pretreatment with KFM and KFB resulted in a significant decrease in the production of aminopyrine N-demethylase in the $CCl_4$-treated rats. KF extract would appear to contribute to alleviate the adveISe effect of $CCl_4$ treatment by enhancing the hepatic antioxidant defense system.

• 대한의생명과학회지
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• 제5권1호
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• pp.51-58
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• 1999

실험동물에 있어서 $CCl_4$에 의한 급성 간손상시 피부조직의 oxygen free radical 대사효소 활성 변동을 검토하기 위해 흰쥐에 $CCl_4$와 olive oil의 동량 혼합액을 체중 100g당 0.1 ml씩 복강으로 투여하여 처치하였다. $CCl_4$ 투여로 인한 혈청 alanine aminotransferase 및 xanthine oxidase (XO) 활성은 현저히 증가되었으며 체중당 간무게 (%)및 간조직의 malondialdehyde함량 역시 유의하게 증가되었다. 그리고 병리조직 검사에서도 $CCl_4$투여군에서 간조직의 괴사성 병변이 관찰되었다. 따라서 $CCl_4$를 투여한 실험동물이 급성 간손상 모델로 확인되었다. 이와 같은 간손상 실험동물의 피부조직중 oxygen free radical의 생성 효소인 XO 활성은 대조군과 별다른 차이를 볼 수 없었으나 oxygen free radical의 scavenging 효소인 superoxide dismutase, glutathione peroxidase 및 catalase 활성은 대조군에 비하여 유의하게 감소되었다. 또한 세포화학적 검사에서 cerrous perhydroxide과립이 간손상 실험동물의 피부조직에서 많이 나타났다. 이상 실험결과는 $CCl_4$에 의한 급성 간손상 유도 실험동물의 피부조직에 $H_2O$$_2$의 축적이 나타나는 현상을 시사해주고 있다.