• Title/Summary/Keyword: CCL4 induced hepatic injury

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The Efficacy of Needle-Acupuncture and Moxibustion at BL18 on Hepatic Injury in Dogs (간유(肝兪)(BL18)에 대한 자침 및 뜸 요법의 개 간 손상 회복에 미치는 효과)

  • Jun, Hyung-Kyou;Lee, Chang-Seok;Lee, Jung-Yeon;Lee, Sang-Eun;Song, Kun-Ho;Park, Bae-Gun;Cho, Sung-Whan;Kim, Duck-Hwan
    • Journal of Veterinary Clinics
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    • v.24 no.1
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    • pp.10-14
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    • 2007
  • The present study was performed to elucidate the recovery effect of needle-acupuncture (needle-AP) and moxibustion treatments at Gan Shu (BL18) on $CCl_4$ induced hepatic injury in dogs, Total 9 clinically healthy experimental dogs (1 to 2 years old, 2.3-5.3kg body weight) were divided into control (3 dogs), needle-AP (3 dogs) and moxibustion (3 dogs) groups, respectively. Hepatic iniw was induced by intraperitoneal injection with $CCl_4$ (olive oil : $CCl_4=1:1,\;1ml/kg$, once/day). As far the treatments in each group, control group was not treated at all after induction of the hepatic injury till the end of experiment. Needle-Af group was treated by AP at BL18 (once/day, 20 minutes) from the next day of induction of the hepatic injury for 11 days. Moxibustion group was also treated with commercial moxa at BL18 (once/day, 20minutes) for 11days. The changes of the serum alanine transaminase(ALT), aspartate transaminase(AST) and gamma glutamyl transpeptidase (GGT) activities were investigated on pre, 0, 1, 3, 5, 7 and 11 days after hepatic injury, respectively. Histopathological changes were also investigated in the liver tissues on day 11 in experimental and control groups. The results obtained in the present study were as follows. In needle-AP group, they showed significant lower values on the 1st (p<0.05) and $3^{rd} day (p <0.05)$ in serum ALT activities, and the $11^{th}$ day in serum GGT activities, compared with those of control group, respectively. However, the significances were not detected in serum AST activities of needle-AP group by comparison with those of control group. In moxibustion group, they showed significant low values on the $1^{st}(p<0.05)$, 3rd day (p<0.05) and $5^{th}$ day (p<0.05) in serum ALT activities, compared with those of control group, respectively. However, significances were not detected in serum GGT and AST activities of moxibustion group by comparison with those of control group. Among the experimental groups, the significant low values were found on $1^{st}\;and\;3^{rd}$ day in serum ALT activities (p<0.05), and $3^{rd}\;and\;5^{th}$ day in serum GGT activities (p<0.05) in needle-AP group, compared by those of moxibustion group, respectively. In addition, the marked recovery findings of histopathological changes in experimental groups were found, compared by those of control group: mild vacuolar degeneration and necrosis findings in needle-AP group, and moderate vacuolar degeneration and necrotic findings in moxibustion group were found, in contrast to severe changes such as accumulation of bile juice, vacuolar degeneration and necrotic findings observed in control group. In conclusion, needle-AP and moxibustion treatments at BL-18 were effective for the recovery for $CCl_4$ induced hepatic injury and needle-AP was more effective than that of moxibustion in dogs.

Curcuma Extract Enhances Hepatoprotective Action of Silymarin in Experimental Liver Damage Models (실리마린의 간보호 작용에 미치는 쿠쿠마 추출물의 영향)

  • 이기명;함기백;조성원;오태영;최설민;김정훈;안병옥;권종원;김원배
    • Biomolecules & Therapeutics
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    • v.10 no.1
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    • pp.12-18
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    • 2002
  • Silymarin and curcumin have been used for supportive treatment of liver disease of difffrent etiology due to their hepatoprotective activities. The present study was carried out to investigate the hepatoprotective efffcts of silymarin and/or curcuma extract against hepatotoxins induced liver injury. To investigate hepatoprotective effects, the silymarin and/or curcuma extract were pre-treated orally to experimental animals. And thereafter a single dose of hepatotoxin, carbon tetrachloride ($CCl_4$) and acetaminophen were administered through oral or intraperitoneal route, respectively. Chronic liver damage was induced by subcutaneous injection of $CCl_4$ for 3 weeks (2 times/week). Hepatoprotective and therapeutic effects were monitored by estimating serurn ALT and AST levels and by measuring hepatic glutathione (GSH) and malondialdehyde (MDA)levels. Collagen type 1 was detected with irnrnunostaining to assess fibrosis. The results showed that the mix-ture of silymarin and curcuma extract significantly reduced serum biochemistry levels and MDA levels com-pared with those of control group in both acute and chronic animal models. In antifibrotic effect, the relative hepatic collagen content was significantly decreased by silymarin and/or curcuma extract treatment. It was concluded that the complex of silymarin and curcuma extract have a both hepatoprotective and therapeutic effect synergically in rat liver injury induced by heptotoxins.

Saccharina japonica Extract Protects against Carbon Tetrachloride-induced Hepatotoxicity in Rats (사염화탄소로 유도된 흰쥐의 간손상으로부터 다시마(Saccharina japonica) 추출물의 보호효과)

  • Kim, Mi-Kyung;Kim, In-Hye;Nam, Taek-Jeong
    • 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.

The Effect of WY-91 Preparation on Experimental Liver Injury in Mice (실험적 간장해에 대한 WY-91제제의 영향)

  • Han, Sang Soo;Sohn, Dong Hwan;Kim, Jae Baek
    • Korean Journal of Clinical Pharmacy
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    • v.3 no.2
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    • pp.157-162
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    • 1993
  • The present study was designed to examine the effect of tested preparation, WY-91 (consisting of ginseng extract, ganoderma extract and Royal jelly) on alcohol-induced unusual metabolism(such as blood glucose(BG), triBlyceride(TG), and blood urea nitrogen(BUN) level in blood) and nrperinlental liver injury($CCl_4$ and high fat diet) in mice. WY-91 lowered the level of blood glucose (BG),triglyceride(TG) and blood urea nitrogen(BUN) induced by alcohol in a dose-dependent manner. This preparation could protect hepatic function from a damages caused by high fat diet and $CCl_4$ administration(p.o.).

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Effect of Hepatic Damage on the Toluene Metabolism in Carbon Tetrachloride Pretreated-Rats (흰쥐에 있어서 톨루엔 대사에 미치는 간손상의 영향)

  • Cha, Sang-Eun;Yoon, Chong-Guk;Lee, Sang-Il
    • Toxicological Research
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    • v.14 no.3
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    • pp.321-328
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    • 1998
  • This study was performed to evaluate the effect of liver damage on toluene metabolism in rats pretreated with carbon tetachloride. Liver damage in rats was induced by administration of 0.1ml of carbon tetrachloride per 100g of body wight intraperitoneally every day for four weeks except the last day before sacrifice. One day before sacrifice, toluene was administered to the animals instead of carbon tetrachloride. Rats were sacrificed at the 1st, the 2nd, the 3rd and the 4th week after the first administration of carbon tetachloride. Based on the histopathological findings, liver weight and serum alanine aminotransferase, the $CCl_4$-preteated group was found to have gradual severe liver damage. Especially the degree of liver injury became increasingly severe throughout the whole course of the experiment. The contnts of hippuric acid in urine lower in the all groups pretreated with $CCl_4$than that of the control. The contents of hepatic cytochrome P450(CYP), benzylalcohol dehydrogenase and benzaldehyde dehydrogenase activities were decreased in $CCl_4$-pretreated rats than those of the control. The $CCl_4$treated animals showed the gradual decreased activities of these enzyme as injection times elapsed. Km values of the benzylalcohol dehydrogenase in pooled liver samples from $CCl_4$-pretreated or control groups were similar. On the other hand, Vmax values of the $CCl_4$-pretreated group was lower than of the control. Therefore, it can be concluded that reduction of the toluene metabolism in damaged rat liver induced with $CCl_4$was due to the inhibition of CYP content, bezylalcohol and benzaldehyde dehydrogenase activities which related with toluene metabolic enzyme system.

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Effect of Onion Extract on the Carbon Tetrachloride-induced Liver Injury in Mouse

  • Lee, Kyung-Jin;Kim, Deok-Song;Kim, Jong-Sun;Chin, Jong-Eun;Kim, Jun-Ho;Na, Myung-Suk;Lee, Jong-Bin
    • Preventive Nutrition and Food Science
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    • v.8 no.2
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    • pp.130-136
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    • 2003
  • The protective effects of onion extract (OE), onion powder extracted in ethanol for 2 days. on carbon tetrachloride ($CCl_4$)-induced hepatotoxicities and the possible mechanisms involved in this protection were investigated in mice. Pretreatment with OE prior to the administration of $CCl_4$ significantly reduced the increase in serum alanine and aspartate aminotransferase activities and hepatic lipid peroxidation in a dose-dependent manner. In addition, pretreatment with OE significantly prevented the depletion of reduced glutathione content in the liver of $CCl_4$-intoxicated mice. $CCl_4$-induced hepatotoxicity was also prevented, as indicated by a liver histopathologic findings. The effects of OE on the cytochrome P450 (P450) 2E1, the major isozyme involved in $CCl_4$ biotransformation were investigated. Treatment of mice with OE resulted in a significant decrease in P450 2E1-dependent p-nitrophenol and aniline hydroxylation in a dose-dependent manner. Consistent with these observations, the P450 2E1 expressions were also decreased, as determined by immunoblot analysis. OE also exhibited antioxidant effects in FeCl$_2$-ascorbate induced lipid peroxidation in rat liver homogenates and in superoxide radical scavenging activity. These results show that the protective effects of OE against the $CCl_4$-induced hepatotoxicity may be due to its ability to block bioactivation of $CCl_4$, mainly tty inhibiting the expression and activities of P450 2E1 and by scavenging free radicals.

Swertiamarin ameliorates carbon tetrachloride-induced hepatic apoptosis via blocking the PI3K/Akt pathway in rats

  • Zhang, Qianrui;Chen, Kang;Wu, Tao;Song, Hongping
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.1
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    • pp.21-28
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    • 2019
  • Swertiamarin (STM) is an iridoid compound that is present in the Gentianaceae swertia genus. Here we investigated antiapoptotic effects of STM on carbon tetrachloride ($CCl_4$)-induced liver injury and its possible mechanisms. Adult male Sprague Dawley rats were randomly divided into a control group, an STM 200 mg/kg group, a $CCl_4$ group, a $CCl_4+STM$ 100 mg/kg group, and a $CCl_4+STM$ 200 mg/kg group. Rats in experimental groups were subcutaneously injected with 40% $CCl_4$ twice weekly for 8 weeks. STM (100 and 200 mg/kg per day) was orally given to experimental rats by gavage for 8 consecutive weeks. Hepatocyte apoptosis was determined by TUNEL assay and the expression levels of Bcl-2, Bax, and cleaved caspase-3 proteins were evaluated by western blot analysis. The expression of $TGF-{\beta}1$, collagen I, collagen III, CTGF and fibronectin mRNA were estimated by qRT-PCR. The results showed that STM significantly reduced the number of TUNEL-positive cells compared with the $CCl_4$ group. The levels of Bax and cleaved caspase-3 proteins, and $TGF-{\beta}1$, collagen I, collagen III, CTGF, and fibronectin mRNA were significantly reduced by STM compared with the $CCl_4$ group. In addition, STM markedly abrogated the repression of Bcl-2 by $CCl_4$. STM also attenuated the activation of the PI3K/Akt pathway in the liver. These results suggested that STM ameliorated $CCl_4$-induced hepatocyte apoptosis in rats.

Effect of Fermented Blackberry Drinks Formed from Radiation-induced Mutant on Liver Repair Capacity in Rats (방사선 유도 돌연변이체 블랙베리로 제조한 발효음료의 간 손상 회복 효과)

  • Cho, Byoung Ok;So, Yangkang;Lee, Chang Wook;Cho, Jung Keun;Woo, Hyun Sim;Jin, Chang Hyun;Jeong, Il Yun
    • Journal of Radiation Industry
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    • v.7 no.1
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    • pp.81-85
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    • 2013
  • This study was conducted to investigate the effect of fermented blackberry drinks (BD) on carbon tetrachloride ($CCl_4$)-induced liver injury in rats. Male Sprague-Dawley rats were randomly divided into four groups with 6 rats per group: control, $CCl_4$, $CCl_4$ plus BD $3ml\;kg^{-1}$, and $CCl_4$ plus BD $6ml\;kg^{-1}$. We found that the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly increased and the activity of antioxidant enzyme glutathione peroxidase (GPx) in the liver was decreased in rats treated with $CCl_4$ alone when compared with the control group. However, the administration of BD attenuated the levels of serum AST and ALT in $CCl_4$-treated rats. Moreover, the administration of BD significantly increased the activity of GPx in $CCl_4$-treated rat livers. Taken together, these results suggest that BD could protect the liver from $CCl_4$-induced hepatic damage.

Effects of Administration of CCl$_{4}$ on Liver Function in Rats 1. Clinical Signs and Blood Chemical Values (사염화탄소(CCI$_{4}$)의 투여가 쥐의 간기능에 미치는 영향 1. 임상증상 및 혈액화학치)

  • 강정부;이은석;허주헝
    • Journal of Veterinary Clinics
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    • v.14 no.2
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    • pp.268-272
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    • 1997
  • This study was performed to estimate the clinical signs and biochemical para meters of indicator on acute hepatic injury induced by the administration of CCl$_{4}$ in rats. Minor behavioral changer brittleness of skin hair and decreased volume of water and food intake were observed in rats after 2 hours of $CCl_{4}$ administration compared to control group. Concentration of serum albumin has shown lower than that of control group. However concentration of total bilirubin has shown higher than that of control group. As times go onto serum LDH activity was significantly increased compared to control Broup. Serum CPK activity hasn't shown change compared to control group. Passive hemagglutination that of afetoprotein was shown negative reaction in all the treatment groups and control group.

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Pharmacological Effects of the Allium victorialis var. platyphyllum Extracts on the Rats Induced by Streptozotocin, Poloxamer-407, $CCl_4$ and D-Galactosamine (Streptozotocin, Ploxamer 407, $CCl_4$ 및 D-Galactosamine으로 유도한 병태모델 흰쥐에 대한 산마늘 추출물의 약리효과)

  • Choi, Jong-Won;Lee, Kyung-Tae;Kim, Won-Bae;Park, Kwang-Gyun;Jung, Hyun-Ju;Park, Hee-Juhn
    • Korean Journal of Pharmacognosy
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    • v.34 no.3 s.134
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    • pp.250-255
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    • 2003
  • To develop Allium victorialis var. platyphyllum (Liliaceae) for an available functional food, pharmacological experiments on the extracts of this plant were undertaken in the rat treated with streptozotocin, poloxamer-407 and $CCl_4$. The two MeOH extracts were obtained from the leaves and the bulbs, respectively. The three agents, streptozotocin, poloxamer-407 and $CCl_4$, were treated to induce diabetes mellitus, hyperlipidemia and hepatic injury, respectively. Treatment with the leaf extract lowered blood glucose by 24.9% at 200 mg/kg (p.o.) in the STZ-treated rat and prohibited the increase of body weight, water consumption and food intake. This exσact also significantly decreased not only thε plasma cholesterol and triglyceride in the poloxamer-407-treated rat by 35.3% but also serum ALT by 49.0%. The potency was found by overall estimation on the experimental results as followings: 200 mg/kg leaf extract> 200 mg/kg bulb extract> 100 mg/kg leaf exσact> 100 mg/kg bulb extract. These results suggested that this plant might have the availability for a functional food. It was also suggested that the leaves are more effective than the bulbs for the functional vegetable, especially in hyperlipidemia and hepatic injury.