CCl_4로 간손상을 유도한 랫드의 신장과 비장에서 교원질 단백질의 정량적인 변화관찰

김기영,조재진,유병수 원광대학교 생체재료·매식연구소 1999 원광생체재료·매식 Vol.8 No.1

건율제조탕이 CCl₄로 유발(誘發)된 간손상(肝損傷) 백서(白鼠)에 미치는 영향(影響)

김정렬,김혁,양상묵,김달래,전종원,Kim, Jung-Yul,Kim, Hyuk,Yang, Sang-Mook,Kim, Dal-Rae,Jeon, Jong-Weon 사상체질의학회 2004 사상체질의학회지 Vol.16 No.3

1. Objectives This study was carried out to investigate the effects of Gunyuljejo-tang on the $CCl_4$-induced Liver Damage in Rats. 2. Methods Sprague-Dawley rats were devided into 5 experimental groups : Normal, $NS+CCl_4$(Solid extract of $CCl_4$ injection group after Normal Saline feed), $GYJJT+CCl_4$(Solid extract of $CCl_4$ injection group after Gunyuljejo-tang feed), $CCl_4+NS$(Normal Saline feed group after $CCl_4$ injection), $CCl_4+GYJJT$(Solid extract of Gunyuljejo-tang feed group after $CCl_4$ injection). Biochemical assays for serum enzyme activities such as AST, ALT, ALP, BUN, Creatinine, Uric Acid, Total Protein, Albumin, Total Cholesterol, Triglyceride, Glucose, and mRNA Revelation of Cytochrome p450 and activities such as LPO, GSH, GST, Glutathione Reductase, Glutathione Peroxidase, SOD, Catalase, Hydroxyproline, and ${\beta}$-Glucuronidase were performed. 3. Results (1) $GYJJT+CCl_4$ showed lower revelation of Cytochrome p450. (2) $GYJJT+CCl_4$ showed higher GSH activity than $NS+CCl_4$, $CCl_4+GYJJT$ showed higher GSH activity than $CCl_4+NS$ injection significantly. (3) $GYJJT+CCl_4$ showed higher GST activity than $NS+CCl_4$. $CCl_4+GYJJT$ showed higher GST activity than $CCl_4+NS$ significantly. (4) $GYJJT+CCl_4$ showed higher Glutathione Peroxidase activity than $NS+CCl_4$, $CCl_4+GYJJT$ showed higher Glutathione Peroxidase activity than $CCl_4+NS$ significantly. (5) $CCl_4+GYJJT$ showed higher SOD activity than $CCl_4+NS$ significantly. (6) $CCl_4+GYJJT$ showed higher Catalase activity than $CCl_4+NS$ significantly. (7) $GYJJT+CCl_4$ showed lower Hydroxyproline than $NS+CCl_4$ significantly, $CCl_4+GYJJT$ showed higher Hydroxyproline than $CCl_4+NS$ significantly. (8) $GYJJT+CCl_4$ showed higher ${\beta}$-Glucuronidase activity than $NS+CCl_4$, $CCl_4+GYJJT$ showed higher ${\beta}$-Glucuronidase activity than $CCl_4+NS$ significantly. 4. Conclusions Gunyuljejo-tang has the recovering effects on the $CCl_4$-induced Liver Damage significantly.

CCl₄전처치한 흰쥐에 Cyclohexane 투여가 간손상에 미치는 영향

윤종국,김현희 한국독성학회 2003 Toxicological Research Vol.19 No.2

TO evaluate an effect of cyclohexane treatment on the degree of liver damage, rats were induced liver damage with 10 or 17 times $CCl_4$ injection (0.1 m1/100 g body wt., 50% $CCl_4$ dis-solved in olive oil) at intervals of every other day. Cyclohexane (1.56 g/kg body wt., i.p.) was administrated to the animals at 48 hours after the last pretreatment of $CCl_4$ . Rats were sacrificed at 4 hours after injection of cyclohexane. On the basis of histopathological findings, liver weight/body weight (LW/ BW, %), activities of serum alanine aminotransferase (ALT), xanthine oxidase (XO) and akaline phosphatase (ALP), and contents of liver protein and manlondialdehyde (MDA), $CCl_4$ -pretreatment induced liver damage. And $CCl_4$ 17 times treated group showed more severe liver damage than $CCl_4$ 10 times treated group. Administration of one dose of cyclohexane to $CCl_4$ 10 times treated animals resulted in the enhanced liver damage; liver necrosis with proliferation of fibroblast and bile duct abnormality, and increase in hepatic MDA content and the activities of serum ALP and ALT, But the enhanced liver damage was not found in $CCl_4$ 17 times treated animals. Serum cyclohexanone concentrations at 4 or 8 hours after injection of cyclohexane were higher in all liver damaged groups than normal group and were somewhat higher In $CCl_4$ 17 times treated animals than $CCl_4$ 10 times treated ones. Among the oxygen free radical metabolizing enzymes, hepatic cytochrome P45O dependent aniline hydroxylase (CYPdAH) activity in cyclohexane metabolizing enzyme system was meaningfully increased by the injection of cyclohexane to the liver damaged rats, with increased Vmax and high affinity to aniline. LW/BW (%) and activities of serum XO and ALT were more significantly increased in liver damaged groups than normal group by administration of cyclohexanone. In conclusion, it is assumed that an enhancement of liver damage by injection of one dose of cyclohexane to liver damaged animals might be caused by oxygen free radicals and cyclohexanone.

Characterization of C-C motif chemokine ligand 4 in the porcine endometrium during the presence of the maternal–fetal interface

Lim, Whasun,Bae, Hyocheol,Bazer, Fuller W.,Song, Gwonhwa Elsevier 2018 Developmental Biology Vol.441 No.1

<P><B>Abstract</B></P> <P>Chemokines and their receptors play a crucial role in embryo implantation at the maternal–fetal interface during pregnancy. In this study, we investigated the role of CCL4 in development of the porcine endometrium in the early gestational period. Porcine CCL4 showed high similarity with the human counterpart, and mRNA expression of <I>CCL4</I> and its receptor (<I>CCR5</I>) was predominantly present in the endometrium during early pregnancy. Treatment with CCL4 increased proliferation of porcine uterine luminal epithelial (pLE) cells by activation of PI3K and MAPK signal transduction. In addition, CCL4 recovered the endoplasmic-reticulum stress–reduced proliferation and decreased the unfolded protein response in pLE cells. Besides, the lipopolysaccharide-activated NF-κB pathway was suppressed in response to CCL4 in pLE cells. Inhibition of CCR5 decreased the proliferation of pLE cells and activation of the PI3K and MAPK pathways by CCL4. Furthermore, CCL4 enhanced conceptus-maternal interactions between porcine trophectoderm (pTr) cells and pLE cells during early pregnancy by activating expression of migration and implantation-related genes. Collectively, the results suggest that CCL4 may improve successful implantation in early pregnancy in pigs.</P> <P><B>Highlights</B></P> <P> <UL> <LI> CCL4 increases the proliferation of porcine uterine luminal epithelial cells. </LI> <LI> CCL4 activates intracellular PI3K and MAPK signaling transduction. </LI> <LI> CCL4 suppresses ER stress and inflammation by regulating UPR and NF-κB signaling. </LI> <LI> CCL4 is important for uterine receptivity and placentation in early pregnancy. </LI> </UL> </P>

알코올과 CCl_4 동시투여에 의한 간경변 유도와 저용량 LPS의 간손상 보호효과 : Can the Lipopolysaccharide Prevent Liver Injury Induced by Alcohol and CCl_4?

채희복,장이찬,박선미,손보라,성노현,최재운 대한간학회 2002 Clinical and Molecular Hepatology(대한간학회지) Vol.8 No.2

목적 : 쥐에서 알코올과 CCl4를 동시에 투여한 알코올성 간경변 동물실험모델을 만들어 보고자 하였다. 추가로 저용량의 LPS는 간으로부터 NO를 유리하여 알코올에 의한 급성간손상을 보호하는 효과가 있다고 알려진 바, 본 동물실험모델에서도 간경변으로의 진행을 차단하는 효과가 있는지 간조직의 염증과 섬유화 정도를 비교함으로써 알아보고자 하였다. 대상과 방법 : Sprague-Dawley계 암컷 백서 20마리를 사용하였다. 제 1군 8마리는 알코올만을, 제 2군 6마리는 알코올과 CCl4를, 제 3군 6마리는 알코올, CCl4 그리고 저용량 LPS를 10주간 투여한 뒤 쥐를 희생시켜 혈액과 간조직을 채취하였다. AST, ALT, AP, 간조직내 염증과 섬유화 정도를 측정하여 각 군간에 비교하였다. 결과 : (1) 혈청 AST치는 제 1군에서 142±26, 제 2군에서 175±50, 제 3군에서 169±6.4이었고, ALT치는 40±8.7, 72±24, 65±7.7이었으며, AP(IU/L)치는 317±128, 669±341, 796±135이었다. ALT의 경우 제 1군과 제 3군 사이에, AP의 경우 제 1군과 2군, 그리고 제 1군과 제 3군 사이에 각각 유의한 차이가 있었다. (2) 간의 조직학적인 부위에 따른 염증정도와 섬유화에 대한 결과는 알코올만을 투여하였던 대조군에서는 염증 및 섬유화가 거의 나타나지 않거나 경도에 그친 반면에, 제 2군과 제 3군에서는 간문맥주위, 그리고 간중심정맥주위에서 염증성 변화와 섬유화가 거의 비슷한 정도로 나타났으며 양 군간에 통계적인 차이는 없었다. (3) 격막 섬유화 내지 간경변의 소견을 나타낸 예는 전체 12마리 중 9마리에 해당하여 간경화 유도율은 67%이었다. 결론 : 본 실험을 통하여 저용량 LPS에 의한 간손상보호효과를 증명할 수는 없었다. 알코올과 CCl4를 쥐에게 병용 투여한 결과 중등도 이상의 섬유화가 67%에서 유도되어 양호한 결과를 나타내었다. 향후 복강내 유리 NO의 양을 정량하는 후속연구가 필요하다고 생각된다. Background/Aims: It is well known that alcohol enhances the toxicity of CCl4. We tried to establish an alcoholic liver cirrhosis model by administration of alcohol and CCl4 to rats. We also wanted to know the hepatoprotective effect of low doses of lipopolysaccharide(LPS) in this animal model. Methods: Of 20 female adult rats, 8 were ingested with alcohol ad libitum(group 1) Another 6 were ingested with 10% alcohol and 50% 1mL/kg CCl4 intragastrically by Sonde twice a week(group 2) The remaining 6 were ingested with 10% alcohol, CCl4, and 0.1mg/kg LPS intraperitoneally twice a week(group 3) The fibrosis was evaluated semiquantitatively on a scale of 0(none) to 3(cirrhosis). Results: 1) After 10 weks, septal fibrosis or cirrhosis was produced in 9 out of 12 rats in groups 2 and 3 but there was no fibrotic change in group 1. 2) There was no significant difference in pathological grading between groups 2 and 3. Conclusions: Hepatic fibrosis or cirrhosis can be sufficiently induced by alcohol and repetitive CCl4 ingestion for 10 weeks. We can not prove the hepatoprotective effect of low dose LPS by semiquantitative evaluation of pathological grading.(Korean JHepatol 2002;8:173-178)

사염화탄소 투여로 인한 랫드의 급성 간 손상에 대한 루틴의 예방 효과

황의경 한국임상수의학회 2013 한국임상수의학회지 Vol.30 No.1

This study was performed to investigate hepatoprotective effect of rutin on acute hepatic damage induced by carbon tetrachloride in rats. Twenty-four male Sprague-Dawley rats were randomly divided into four groups; normal control group, CCl4 control group, two rutin treatment groups (rutin 200+CCl4 and rutin 400+CCl4). Dissolving vehicles were applied to the rats in the normal control group. The rutin was administrated to the rats in rutin 200+CCl4 and rutin 400+CCl4 groups at the levels of 200 mg/kg and 400 mg/kg, 3 consecutive days orally, with 24 hours interval before inoculating CCl4. CCl4 was intraperitoneally administered an hour after the last treatment of rutin to the rats in every group except the normal control group. The body weight of rats in CCl4 control group were significantly lower than other groups (p < 0.05), but the liver weight and relative liver weight were higher than normal control group (p < 0.05). The activities of ALT, AST, ALP, GTP, LDH and the level of total bilirubin in sera of rats in CCl4control group were higher and the levels of total protein, albumin and globulin were lower than the normal group (p < 0.05). The activities of ALT, AST, ALP, GTP, LDH and the level of total bilirubin in rutin 200+CCl4 and rutin 400+CCl4 groups were lower than CCl4 control group (p < 0.05). Therefore the pre-treatment of rutin before CCl4inoculation in rats effectively inhibited the elevation of serum ALT, AST and total bilirubin which are the parameters of hepatic damage.

냉매 R-10(CCl4)과 CH4 혼소 화염특성 전산해석 연구

신미수,김용주,장동순,이용국,이강우 한국폐기물자원순환학회 2014 한국폐기물자원순환학회지 Vol.31 No.8

Considering the high potential of the widely-used halogenated hydrocarbons on the global warming and ozone depletion, the development of effective thermal destruction methods of these compounds are quite urgent and indispensible. As part of the research efforts of this area, the destruction of CCl4 and flame characteristics have been investigated numerically by the co-firing CCl4 with CH4 in an industrial LNG-fired combustor as a function of molar ratio of the CCl4 to CH4 using a commercial code of STAR-CCM+. Considering a broad range of Damkohler number associated with the process of intensive CHCs (Chlorinated hydrocarbons) combustion with auxiliary fuel together with the inhibition reaction especially near flammability limits, a proper combustion modeling of CCl4 thermal destruction is quite desirable. In this study, however, after careful review of the literature about the flame characteristics of halogenated hydrocarbon together with the previous study about the modeling of the CCl4 flame based on the data of burning velocity, the eddy breakup turbulent combustion model was employed since it is quite reasonably assumed that chain branching reaction looks dominant in most flame region over the halogenated inhibition effect in strong turbulent reacting flows. One of the most useful results based on this study is that; without any incorporation of flame inhibition effect, the length of co-fired flame increases steadily as the ratio of CCl4 to CH4 (R) increases from 0.0, 0.1, 0.2 to 0.5, and 1.0 together with the increase of the maximum flame and exit gas temperature. The reason of the increase of the flame length with the increase of flame temperature can be explained by the presence of the additional CCl4 fuel with low heating value. Further a detailed discussion has been made on the thermal destruction of CCl4 together with the Cl2 concentration by Deacon reaction.

냉매 R-10(CCl4)과 CH4 혼소 화염특성 전산해석 연구

신미수,김용주,장동순,이용국,이강우 한국폐기물자원순환학회 2014 한국폐기물자원순환학회지 Vol.31 No.8

Considering the high potential of the widely-used halogenated hydrocarbons on the global warming and ozone depletion, the development of effective thermal destruction methods of these compounds are quite urgent and indispensible. As part of the research efforts of this area, the destruction of CCl4 and flame characteristics have been investigated numerically by the co-firing CCl4 with CH4 in an industrial LNG-fired combustor as a function of molar ratio of the CCl4 to CH4 using a commercial code of STAR-CCM+. Considering a broad range of Damkohler number associated with the process of intensive CHCs (Chlorinated hydrocarbons) combustion with auxiliary fuel together with the inhibition reaction especially near flammability limits, a proper combustion modeling of CCl4 thermal destruction is quite desirable. In this study, however, after careful review of the literature about the flame characteristics of halogenated hydrocarbon together with the previous study about the modeling of the CCl4 flame based on the data of burning velocity, the eddy breakup turbulent combustion model was employed since it is quite reasonably assumed that chain branching reaction looks dominant in most flame region over the halogenated inhibition effect in strong turbulent reacting flows. One of the most useful results based on this study is that; without any incorporation of flame inhibition effect, the length of co-fired flame increases steadily as the ratio of CCl4 to CH4 (R) increases from 0.0, 0.1, 0.2 to 0.5, and 1.0 together with the increase of the maximum flame and exit gas temperature. The reason of the increase of the flame length with the increase of flame temperature can be explained by the presence of the additional CCl4 fuel with low heating value. Further a detailed discussion has been made on the thermal destruction of CCl4 together with the Cl2 concentration by Deacon reaction.

Chitosan Oligosaccharides Prevent CCl4-induced Nephrotoxicity in the Rat Kidney

( Ki Young Kang ),( Jung Woo Kim ) 한국키틴키토산학회 2009 한국키틴키토산학회지 Vol.14 No.3

Carbon tetrachloride (CCl4) is a potent hepatotoxic and nephrotoxic material. CCl4-induced organotoxicity is resulted from the reactive radicals produced by biochemical processes. Recently, it is known that chitosan oligosaccharides (COS) have antioxidative properties. Therefore, we intended to investigate the protective effects of COS against the CCl4-induced nephrotoxicity model. CCl4 (1 ml/kg) was administrated to Sprague-Dawley rats once a week for 4 weeks and COS (100 mg/kg) was given daily for 4 weeks. Animals were sacrificed under ether anesthesia, and then whole blood and kidneys were obtained. COS treatment decreases blood urea nitrogen and serum creatinine levels of the CCl4 administered rats in serological analysis. It also prevents histopathological alterations of the CCl4 intoxicated kidney including glomerular congestion, glomerular atrophy and deterioration of renal tubular epithelium. By the immunohistochemistry, COS treatment reduces expressions of the transforming growth factor beta-1 (TGF-β1) and its receptors in the CCl4 intoxicated rat kidney. According to these data, COS is effective renoprotecitve material against the progression of CCl4-induced renal injury.

삼두해정탕가미방이 $CCl_4$ 및 d-Galactosamine에 依하여 誘發된 흰쥐의 肝損傷에 미치는 影響

강재춘,이상민,Kang, Jae-Chun,Lee, Sang-Min 대한한방내과학회 1999 大韓韓方內科學會誌 Vol.20 No.1

In order to investigate the protective effect of Samduhaejungtang-gamibang on the liver injury of rats induced by $CCl_4$ and d-galactosamine, the serum transaminase(GOT& GPT) alkaline phosphatase(ALP), lactic dehydrogenase(LDH) for enzyme activities and triglyceride, total bilirubin amounts for serum component were measured. All animals were divided into 4 groups, those were normal group(untreated), control group(treated with vehicle 0.9% Saline solution), sample Ⅰ group(1500mg/kg administrated), sample Ⅱ group(3000mg/kg administrated). The results were as follows: 1. The inhibitory effects of the serum GOT activities in rats induced by $CCl_4$ were noted in sample Ⅱ group(p<0.01). In serum GPT activities, sample Ⅱ group(p<0.05) only showed the inhibitory effects. 2. The inhibitory effects of the serum ALP activities in rats induced by $CCl_4$ were noted in sample Ⅱ group(p<0.01) 3. The inhibitory effects of the serum LPH activities in rats induced by $CCl_4$ were noted in sample Ⅱ group, but it is not recognized statistically. 4. The increases effects of the serum triglyceride content level in rats induced by $CCl_4$ were inhibited in both sample Ⅰ group(p<0.05) and sample Ⅱ group(p<0.01) 5. The increases effects of the serum total bilirubin content level in rats induced by $CCl_4$ were inhibited in sample Ⅱ group(p<0.05) 6. The inhibitory effects of the serum GOT, GPT activities in rats induced by d-galactosamine were noted in sample Ⅱ group (p<0.001), but sample Ⅰ group was not recognized. 7. The signiticantly inhibitory effects of in the serum LDH activities in rats induced by d-galactosamine were noted in both sample Ⅰ group(p<0.05) and sample Ⅱ group (p<0.001) 8. The increases of the serum ALP content level in rats induced by d-galactosamine were inhibited in sample Ⅱ group(p<0.05) 9. The increases of the serum total bilirubin content level in rats induced d-galactosamine were inhibited in sample Ⅱgroup(p<0.05) According to the above results, it is considered that Samduhaejungtang-gamibang has protective effect against liver injury in rats induced by $CCl_4$ and d-galactosamine. So it is required to study about the actions of mutual relation of medicines and patho-mechanism by experiment.