• Korean Journal of Acupuncture
• /
• 제25권2호
• /
• pp.211-224
• /
• 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
• /
• 제8권4호
• /
• pp.212-218
• /
• 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.

• Environmental Analysis Health and Toxicology
• /
• 제23권4호
• /
• pp.325-335
• /
• 2008

The protective effects of the Naringin, on carbon tetrachloride ($CCl_4$)-induced hepatotoxicity and the possible mechanisms involved in this protection were investigated in mice. Pretreatment with Naringin prior to the administration of $CCl_4$ significantly prevented an increase in serum alanine, aspartate aminotransferase activity and hepatic lipid peroxidation in a dose-dependent manner. In addition, pretreatment with Naringin also significantly prevented the depletion of glutathione (GSH) content in the livers of $CCl_4$-induced mice. However, reduced hepatic glutathione levels was unaffected by treatment with Naringin alone. In addition, Naringin prevented $CCl_4$-induced apoptosis and necrosis, as indicated by a liver DNA laddering. To determine whether caspase-8,-3 pathway involved in $CCl_4$-induced acute liver injury, caspase-8, -3 activities were tested by ELISA. Naringin attenuated $CCl_4$induced caspase-8, -3 activities in mouse livers. $CCl_4$-induced hepatotoxicity was also prevented, as indicated by a liver histopathologic study. The effects of Naringin on the cytochrome P450 (CYP) 2E1, the major isozyme involved in $CCl_4$ were also investigated. Treatment of mice with Naringin resulted in a significant decrease of the CYP2E1-dependent hydroxyl at ion and aniline in a dose-dependent manner. These findings suggest that protective effects of Naringin against the $CCl_4$-induced hepatotoxicity may be due to its ability to block CYP2E1-mediated $CCl_4$ bioactivation and that is also protects against caspase-8, -3 pathway mediated apoptosis.

• 대한의생명과학회지
• /
• 제5권1호
• /
• pp.51-58
• /
• 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.

• 대한한방내과학회지
• /
• 제24권1호
• /
• pp.21-32
• /
• 2003

Objective : The aim of this study is to investigate the inhibitory effect of Injinchunggantang on hepatic sclerosis induced by $CCl_4$. Methods : Weight, liver function test and complete blood cell count, gross findings, and findings on liver tissue of the past(Hematoxylin & Eosin stain, Masson-Trichrome stain) were studied. Results : When it comes to the change of rats' body weight, The $CCl_{4^+}$Injinchunggantang group lost far less weight than The $CCl_{4^-}$only group. In the liver function test, which is focused on various areas such as total cholesterol, alkaline phosphotase, albumin, aspartate transaminase, alanine transaminase, The $CCl_{4^+}$Injinchunggantang group was much more closer to normal limit than the $CCl_4$ only group. In the complete blood cell count, including white blood cell, red blood cell, hemoglobin, hematocrite, platelet, The $CCl_{4^+}$Injinchunggantang group significantly closer to normal limit than $CCl_{4^-}$only group. In the gross findings of hepatic fibrosis models, Injinchunggantang showed inhibitory effect on hepatic fibrosis in the order. In the past findings of hepatic fibrosis models in Hematoxylin & Eosin, Masson-Trichrome staining, the liver in $CCl_{4^-}$only group showed atrophy and necrotic change with white nodules, whereas that of $CCl_{4^+}$Injinchunggantang group showed lesser significant change with the well_preserved tone of the tissue. In the extent of the inhibition of the hepatic fibrosis, the Injinchunggantang group showed statistically significant inhibitory effect(p<0.05) in the sclerosis model. Conclusions : These results show that Injinchunggantang have inhibitory effect on hepatic sclerosis induced by $CCl_4$ and further ultimately prevent liver cirrhosis. To obtain more credible results in this experiment, the invention of a new experimental model more similar to human hepatic sclerosis is still needed.

• 한국식품영양과학회지
• /
• 제27권2호
• /
• pp.326-332
• /
• 1998

The effect of mushroom extracts from Pleurotus ostreatus and Lentinus edodes on carbon tetrachloride(CCl4)-induced hepatotoxicity was investigated. Rats were administered orally each mushroom extract at the dose of 150mg/kg, foolwed by treatment with CCl4. Liver damage was produced in male Sprague-Dawley rats, after 21hrs from dosing with CCl4(0.25ml/kg) which were given intraperitoneally. Liver damage without renal injury was confirmed by measuring plasma enzyme, creatinine and blood analysis and liver analysis. Plasma aminotransferase activity, and levels of cholesterol and triglyceride were analyzed. Plasma alanine aminotransferase and aspartate aminotransferase activities were decreased by 34% and 61.5% in pretreatment group of Lentinus edodes compared with CCl4 treated group, respectively. The adminstration of all mushroom extracts led the plasma cholesterol and triglyceride levels decrease more than the CCl4-treated rats. These results suggest that Lentinus edodes extract protect liver from damage induced by CCl4.

• 생명과학회지
• /
• 제9권3호
• /
• pp.300-307
• /
• 1999

The enzyme activities and antioxidative of tocopherol and ascorbate were investigated at the levels of liver, kidney homogenates and sera of SD-rats intoxicated with tetrachlorocarbon$CCl_4$. GOT and GPT activities of sera in the $CCl_4$ group were 3, 6 times increased compared to normal group. But they tended to decrease significantly in tocopherol and ascorbate administered group. As for BUN and total cholesterol they were the same. HDL-cholesterol in the $CCl_4$group was 42% decreased compared to normal group. HDL-cholesterol was about 26% increased in the tocopherol group and tocopherol ascorbate group compared to $CCl_4$ group. MDA and SOD activities in the liver and the kidney tissue homogenates were significantly increased in $CCl_4$ group compared to normal group. But they were decreased significantly in the tocopherol group and tocopherol-ascorbate group compared to $CCl_4$ group. In view of this study tocopherol and ascorbated were ascorbate were effective on the detoxication of liver and kidney injury.

• Journal of Ginseng Research
• /
• 제19권2호
• /
• pp.108-113
• /
• 1995

Effect of ginseng polysaccharide fraction was examined for $CCl_4$-induced hepatotoxicity in vitro and in vivo. In $CCl_4$-injured primary cultured rat hepatocytes, treatment of the polysaccharide fraction (0.1, 0.3, 1.0 mg/ml) significantly Inhibited the release of LDH and GOT into the culture medium in a dose-dependent manner. Oral administration of the polysaccharide fraction (100, 200 mg/kg) inhibited the decrease of body weight and the increase of the ratio of liver to body weight in $CCl_4$-intoxicated rats. Elevation of GOT, GPT and ALP activity in the serum by $CCl_4$-induced hepatotoxicity was suppressed by administration of ginseng polysaccharide fraction. MDA levels increased in the serum as well as in the liver tissue by treatment with $CCl_4$ showed a tendency to be 연w in the rats given to the polysaccharide fraction. These results suggest that the polysaccharide fraction may be active substance responsible for antihepatotoxic effect of Panax ginseng.

• 대한의생명과학회지
• /
• 제12권4호
• /
• pp.361-370
• /
• 2006

To evaluate an effect of pathological liver damage on the conjugation of cyclohexane metabolites, rats were pretreated with 50% $CCl_4$ dissolved in olive oil (0.1 ml/100 g body weight) 10 or 17 times intraperitoneally at intervals of every other day. On the basis of liver function, the animals pretreated with $CCl_4$ 10 times were identified as acutely liver damaged ones and the animals pretreated with $CCl_4$ 17 times were identified as severly liver damaged ones. To these liver damaged animals, cyclohexane (a single dose of 1.56 g/kg body weight, i.p.) was administered at 48 hr after the last injection of $CCl_4$. The rats were sacrificed at 4 or 8 hr after injection of cyclohexane. The cyclohexane metabolites, cyclohexanol (CH-ol), cyclohexane-1,2-diol (CH-1,2-diol), cyclohexane-1,4-diol (CH-1,4-diol), and their glucuronyl conjugates and cyclohexanone were detected in the urine of cyclohexane treated rats. The urinary concentration of cyclohexane metabolites was generally more increased in liver damaged animals than normal ones, and the increasing rate was higher in $CCl_4$ 17 times injected rats than 10 times injected ones. And liver damaged.ats, especially $CCl_4$ 17 times treated ones, had an enhanced ability of glucuronyl conjugation to CH-ol analogues compared with normal group. Futhermore, CH-1,2 and 1,4-diol were all conjugated with glucuronic acid in $CCl_4$ 17 times injected animals. On the other hand, the increasing rate of activities of hepatic cytochrome P450 dependent aniline hydroxylase, alcohol dehydrogenase and urine diphosphate glucuronyl transferase was higher in 17 times $CCl_4$-treated rats compared with normal and $CCl_4$ 10 times injected animals. Taken all together, it is assumed that an increased urinary excretion amount of cyclohexane metabolites in liver damaged rats might be caused by an increase in the activities of cyclohexane metabolizing enzymes. And enhanced conjugating ability of CH-ol in liver damaged animals and novel finding of conjugating form of CH-1,2 and 1,4-diol might be caused by increase in the activity of hepatic diphosphouridine glucuronyltransferase.

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