BACKGROUND C23,an oligo-peptide derived from cold-inducible RNA-binding protein(CIRP),has been reported to inhibit tissue inflammation,apoptosis and fibrosis by binding to the CIRP receptor;however,there are few repor...BACKGROUND C23,an oligo-peptide derived from cold-inducible RNA-binding protein(CIRP),has been reported to inhibit tissue inflammation,apoptosis and fibrosis by binding to the CIRP receptor;however,there are few reports on its role in liver fibrosis and the underlying mechanism is unknown.AIM To explore whether C23 plays a significant role in carbon tetrachloride(CCl4)-induced liver fibrosis.METHODS CCl4 was injected for 6 weeks to induce liver fibrosis and C23 was used beginning in the second week.Masson and Sirius red staining were used to examine changes in fiber levels.Inflammatory factors in the liver were detected and changes inα-smooth muscle actin(α-SMA)and collagen I expression were detected via immu-nohistochemical staining to evaluate the activation of hematopoietic stellate cells(HSCs).Western blotting was used to detect the activation status of the trans-forming growth factor-beta(TGF-β)/Smad3 axis after C23 treatment.RESULTS CCl4 successfully induced liver fibrosis in mice,while tumor necrosis factor-alpha(TNF-α),IL(interleukin)-1β,and IL-6 levels increased significantly and the IL-10 level decreased significantly.Interestingly,C23 inhibited this process.On the other hand,C23 significantly inhibited the activation of HSCs induced by CCl4,which inhibited the expression ofα-SMA and the synthesis of collagen I.In terms of mechanism,C23 can block Smad3 phosphorylation significantly and inhibits INTRODUCTION At present there is no specific and effective drug for treating liver fibrosis caused by acute or chronic injury.Although preclinical research has made breakthroughs,their suitability as clinical treatments is still unknown.The activation of hepatic stellate cells(HSCs)caused by chronic inflammation is a key process in the development of liver fibrosis and activated HSCs expressα-smooth muscle actin(α-SMA)and transdifferentiate into myofibroblasts with proliferation,migration and secretion abilities,synthesizing the extracellular matrix to deposit in the hepatocyte space and subse-quently forming liver fibrosis[1].Although therapeutic strategies have improved due to past few efforts there is no ideal treatment for hepatic fibrosis[2].Extracellular cold inducible RNA binding protein(CIRP)has been shown to play a role in various acute and chronic inflammatory diseases by promoting tissue inflammation and apoptosis and inducing fibrosis through its receptor Toll-like receptor 4(TLR4)[3].C23 is a recognized competitive inhibitor of CIRP that can competitively bind to CIRP receptors and reduce tissue damage in inflammatory diseases[4].C23 has been shown to significantly reduce serum tumor necrosis factor-alpha(TNF-α),IL(interleukin)-6 and IL-1βlevels.In addition,it can reduce tissue TLR4,TNF-α,IL-6 and IL-1βlevels and inhibit the colocalization of CIRP and TLR4,which plays a significant role in systemic inflammation[5].Re-search has shown that CIRP induces the inflammatory phenotype of lung fibroblasts in a TLR4-dependent manner[6].On the other hand,CIRP is associated with markers of fibrosis andα-SMA is significantly positively correlated with CIRP.Cirp-/-mice exhibit attenuated expression ofα-SMA and collagen(COL1A1 and COL3A1),decreased hydroxyproline content,decreased histological fibrosis scores,and improved pulmonary hypertension[7].C23 inhibited the release of TNF-α,the degradation of IκB and the nuclear translocation of NF-κB in CIRP-stimulated macrophages in a dose-dependent manner and C23 treatment significantly increased the serum levels of lactic dehydrogenase,alanine ami-notransferase,IL-6,TNF-αand IL-1βin septic CLP mice[8].Based on previous research we hypothesized that C23 might alleviate liver fibrosis by inhibiting acute and chronic inflammation.As a selective hepatotoxic chemical carbon tetrachloride(CCl4).can induce inflammation and activate HSCs,promoting liver fibrosis.This study reveals the role and mechanism of C23 in CCl4-induced liver fibrosis in mice.at room temperature for 30 minutes.The gray value of each group was calculated after chemiluminescence.展开更多
AIM To investigate the protective effects of Foeniculum vulgare root bark (FVRB), a traditional Uyghur medicine, against carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice. METHODS Mice were randomly divided...AIM To investigate the protective effects of Foeniculum vulgare root bark (FVRB), a traditional Uyghur medicine, against carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice. METHODS Mice were randomly divided into eight groups (n = 20 each). Except for the normal control group, mice in the rest groups were intraperitoneally injected (i.p.) with 0.1% CCl4-olive oil mixture at 10 mL/kg twice a week to induce liver fibrosis. After 4 wk, mice were treated concurrently with the 70% ethanol extract of FVRB (88, 176, 352 and 704 mg/kg, respectively) daily by oral gavage for 4 wk to evaluate its protective effects. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), hexadecenoic acid (HA), laminin (LN), glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) in liver tissues were measured. Hematoxylin-eosin (H and E) staining and Masson trichrome (MT) staining were performed to assess histopathological changes in the liver. The expression of transforming growth factor beta 1 (TGF-beta 1), matrix metalloprotein 9 (MMP-9) and metallopeptidase inhibitor 1 (TIMP-1) was detected by immunohistochemical analysis. Additionally, TGF-beta 1 and alpha-smooth muscle actin (alpha-SMA) protein expression was measured by Western blot. RESULTS A significant reduction in serum levels of AST, ALT, TG, HA and LN was observed in the FVRB-treated groups, suggesting that FVRB displayed hepatoprotective effects. Also, the depletion of GSH, SOD, and MDA accumulation in liver tissues was suppressed by FVRB. The expression of TGF-beta 1, MMP-9 and TIMP-1 determined by immunohistochemistry was markedly reduced in a dose-dependent manner by FVRB treatment. Furthermore, protective effects of FVRB against CCl4-induced liver injury were confirmed by histopathological studies. Protein expression of TGF-beta 1 and alpha-SMA detected by Western blot was decreased by FVRB treatment. CONCLUSION Our results indicate that FVRB may be a promising agent against hepatic fibrosis and its possible mechanisms are inhibiting lipid peroxidation and reducing collagen formation in liver tissue of liver fibrosis mice.展开更多
AIM:To explore the anti-fibrotic effect of Haobie Yangyin Ruanjian Decoction(HYRD)on CCl4-induced hepatic fibrosis in rats and its modulation on the transforming growth factor(TGF)β-Smad signaling pathway.METHODS:Fif...AIM:To explore the anti-fibrotic effect of Haobie Yangyin Ruanjian Decoction(HYRD)on CCl4-induced hepatic fibrosis in rats and its modulation on the transforming growth factor(TGF)β-Smad signaling pathway.METHODS:Fifty-six healthy Wistar rats were randomly divided into five groups:normal control group(n=6),CCl4-induced hepatic fibrosis group(n=14) and three treatment groups(the treated rats received HYRD via oral administration at daily dosages of 8.2,2.5 and 0.82 g/kg,respectively)of HYRD(n=12,respectively).Experimental hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride solution(CCl4 dissolved in peanut oil,4:6,V/V)with 0.5 mL/100 g body weight for the first time,and then 0.3 mL/100 g body weight twice a week for 8 wk.In the former 2 wk,rats were raised by feedstuffⅠ(80% corn meal,20%lard,0.5%cholesterol).After 2 wk,they were raised by feedstuffⅡ(corn meal and 0.5% cholesterol).Except for the control group,30%alcohol solution was given orally to each rat every other day from the beginning,1 mL for each rat.Liver function parameters and hepatic hydroxyproline content were detected by chromatometry.Serum levels of hyaluronic acid(HA),typeⅣcollagen(CIV),typeⅢprecollagen(PCⅢ)and laminin(LN)were assayed with radioimmunoassay.Deposition of collagen was observed with hematoxylin-eosin staining and collagen staining.Gene expression of TGFβ1 and Smad3 were detected with real-time reverse transcriptase-polymerase chain reaction and Western blotting,respectively.RESULTS:The serum levels of alanine transaminase and aspartate transaminase were increased in the model group compared with the control group(P<0.01),and they were decreased in the three treatment groups compared with the model group.The serum levels of total protein and albumin were decreased in the model group and increased in the three treatment groups.The hepatic hydroxyproline content and serum levels of PCⅢ,HA,LN and CIV were markedly increased in the model group compared with the control group,and decreased in the treatment groups.The gene expression of TGFβ1 and Smad3 was enhanced in the model group compared with the control group,and HYRD could down regulate their expression.CONCLUSION:HYRD can inhibit hepatic fibrosis induced by CCl4 in rats,which is probably associated with its down-regulation on fibrogenic signal transduction of TGFβ-Smad pathway.展开更多
AIM: To investigate the expression and role of activin A in a mouse model of acute chemical liver injury. METHODS: Acute liver injury in C57BL/6 male mice was induced by intraperitoneal injection with carbon tetrachlo...AIM: To investigate the expression and role of activin A in a mouse model of acute chemical liver injury. METHODS: Acute liver injury in C57BL/6 male mice was induced by intraperitoneal injection with carbon tetrachloride (CCl4 ) (0.5 mL/kg, body weight) dissolved in olive oil (1:19 v/v). Mice were sacrificed 1, 3, 5 and 7 d after the treatment. The levels of alanine aminotrans-ferase (ALT) and aspartate aminotransferase (AST) in serum were examined and pathological changes of liver observed by hematoxylin and eosin staining to evaluate the liver injury. Activin A protein levels in serum and hepatic tissue homogenate of mice were detected by enzyme-linked immunosorbent assay, and the expres-sion pattern of activin A protein in livers of mice was examined by immunohistochemistry. Activin type Ⅱ A receptor (ActRⅡA) and Smad3 expressions in the liver were analyzed by real-time quantitative reverse transcription-polymerase chain reaction. In order to further investigate the role of activin A, we also utilized activin A blocking experiment by anti-activin A antibody (500 μg/kg, body weight) injection into mouse tail vein. RESULTS: In CCl4-treated mice, serum ALT and AST levels were significantly increased, compared with that in control mice (P<0.01). Furthermore, the serious necrosis was observed around hepatic portal areas in CCl4-treated mice. Simultaneously, activin A levels in serum and hepatic tissue homogenate of mice treated with CCl4 for 1, 3 and 5 d increased significantly, com-pared with that in control mice (P<0.01). Activin A protein expression in hepatocytes not within the ne-crotic area was also upregulated in mice following CCl4 treatment. Not only activin A, but also ActRⅡA and activin signaling molecule Smad3 mRNA expressions in injury liver induced by CCl4 were significantly higher than that in control liver. In addition, levels of serum ALT and AST in CCl4-treated mice were significantly decreased by injection of anti-activin A antibody to block endogenous activin A action, compared with that in CCl4-treated mice by injection of immunoglobulin G instead of anti-activin A antibody (P<0.01), and the severity of liver injury was also reduced remarkably. CONCLUSION: These data show that activin A is in-volved in CCl4-induced acute liver injury. Blocking ac-tivin A actions may be a therapeutic approach for acute liver injury.展开更多
Objective:To investigate the hepatoprotective activity of Averroha carambola fruit extract against carbon tetrachloride induced hepatic injury.Methods:Hepatotoxicity was induced on albino mice by intraperitoneal admin...Objective:To investigate the hepatoprotective activity of Averroha carambola fruit extract against carbon tetrachloride induced hepatic injury.Methods:Hepatotoxicity was induced on albino mice by intraperitoneal administration of CCl<sub>4</sub>.half an hour after the administration of the last dose of the extract of Averroha carambola fruit.Aqueous extract of the fruit of Averroha carambola was administered at a dose of 0.9 g/kg body weight once daily for seven days.The hepatic injury and its prevention was assessed by the estimation of serum activities of alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,alkaline phosphates（ALP）,glutathione level and histopathological studies of liver.Results:Pre-treatment of mice with the fruit extract of Averrhoea carambola significantly reduced serum levels of ALT,AST and ALP enzyme and significantly increased the liver reduced glutathione levels 24 h after the administration of carbon tetrachloride.A marked improvement in the enzyme activities and the liver reduced glulathione level was observed in the pre-treated mice 4 days after the administration of carbon tetrachloride. Histopathological studies provided supportive evidence for the biochemical analvsis. Conclusions:The aqueous extract of the fruit of Averrhoea carambola has hepatoprotective effect against carbon tetrachloride induced liver damage in mice.展开更多
AIM： To develop a simplified and quick protocol to induce cirrhosis and standardize models of partial liver resection in rats. METHODS： In Fischer F344 rats two modified protocols of phenobarbital-carbon tetrachlori...AIM： To develop a simplified and quick protocol to induce cirrhosis and standardize models of partial liver resection in rats. METHODS： In Fischer F344 rats two modified protocols of phenobarbital-carbon tetrachloride （CCl4） （dilution 50%） gavage to induce cirrhosis （frequency adjusted according to weight, but each subsequent dose was systematically administered） were tested, i.e. the rapid and slow protocols. Prothrombin time （PT） and total bilirubin （TB） were also evaluated. Animals from the rapid group underwent 15% hepatectomy and animals from the slow group underwent 70% hepatectomy. RESULTS： Rapid protocol： This corresponded to 1 gavage/4 d over 6 wk （mortality 30%）. Mean PT was 35.2 ±2.8 s （normal： ld.5 s）, and mean TB was 1.8 ± 0.2 mg/dL （normal： 0.1 mg/dL）. Slow protocol： This cop responded to 1 gavage/6 d over 9 wk （mortality 10%）. Mean PT was 11.8 ± 0.2 s （normal： 14.5 s）, and mean TB was 0.4 ± 0.04 mg/dL （normal： 0.1 mg/dL）. Pathological analyses were performed in both protocols which showed persistent cirrhosis at 3 mo. Rat mortality in the rapid garage group who underwent 15% hepatectomy and in the slow garage group who underwent 70% hepatectomy was 50% and 70%, respectively, CONCLUSION： Our modified model is a simplified method to induce cirrhosis which is rapid （6 to 9 wk）, efficient and stable up to 3 mo. Using this method, ＂Child Pugh A＂ or ＂Child Pugh BC＂ cirrhotic rats were obtained. Our models of cirrhosis and hepatectomy can be used in various situations focusing on postoperative survival.展开更多
The isotherm,mechanism and kinetics of carbon tetrachloride(CT) adsorption by polyacrylonitrile-based activated carbon fiber(PAN-ACF) were investigated in batch reactors and a continuous flow reactor,and the regenerat...The isotherm,mechanism and kinetics of carbon tetrachloride(CT) adsorption by polyacrylonitrile-based activated carbon fiber(PAN-ACF) were investigated in batch reactors and a continuous flow reactor,and the regeneration of PAN-ACF was also studied.Freundlich and Dubinin-Radushkevich(D-R) adsorption equations can well describe the adsorption isotherm.CT is mainly adsorbed on the exterior surface of PAN-ACF with low boundary layer effect and rate-controlling step of intra-particle diffusion.The adsorption dynamics in the batch reactor well fits with the pseudo-first-order model,and the breakthrough curves in the continuous flow reactor can be well described by the Yoon-Nelson model.The ACF can be recycled through thermal regeneration,whereas the adsorption capacity decreases from 7.87 to 4.98 mg/g after the fourth regeneration.78%-94%of CT can be removed from the wastewater of a fluorine chemical plant on a pilot scale,which confirms the efficacy of ACF under industrial conditions.The results indicate that PAN-ACF is applicable to CT removal from wastewater.展开更多
Objective:To investigate the hepatoproteetivc ami antioxidant activity of pentagamavunon-0(PGV-0) against CCl-4-induced hepatic injury in rats.Methods:The groups of animals were administered with PGV-0 at die doses 2....Objective:To investigate the hepatoproteetivc ami antioxidant activity of pentagamavunon-0(PGV-0) against CCl-4-induced hepatic injury in rats.Methods:The groups of animals were administered with PGV-0 at die doses 2.5.5,10,and 20 mg/kg b.w.,p.o.once in a day for 6 days and at day 7 the animals were administrated with carbon tetrachloride(CClj)(20%,2 ml/kg b.w.in liquid paraffin dp.).The effect of PGV-0 on serum transaminase(SGPT),alkaline phosphates(ALP and total bilirubin were determined in CCl-4-indueed hepatotoxicity in rats.Further,the effects of PGV-0 on glutathione(GSU) content,cutalase(CAT) and NO free radical scavenging activity also were investigated.Results:The results demonstrated that PCV-0 significantly reduced the activity of SGPT,serum ALP and total bilirubin in CCl-4 induced rat hepatotoxicity.PGV-0 has effect on the antioxidant and free radical defense system.It prevented the depletion level of GSH and decrease activity of CAT in CCl-4-induced liver injury in rats.PCV-0 also demonstrated the free radical scavenger effects on NO free radical scavenging activity with ES value of 32.32μM. Convulsion:All of our findings suggests that PGV-0 could protect the liver cells from CCl-4- induced liver damages and the mechanism may through the antioxidative effect of PGV-0 to prevent the accumulation of free radicals and protect the liver damage.展开更多
Objective:To investigate the hepatoprotective and antioxidant activities of Alchornea cordifolia (A.cordifolia) leaf extract.Methods:Various solvent fractions of the methanol extract of the leaf of the plant.4.cordifo...Objective:To investigate the hepatoprotective and antioxidant activities of Alchornea cordifolia (A.cordifolia) leaf extract.Methods:Various solvent fractions of the methanol extract of the leaf of the plant.4.cordifolia Mull.Arg(Fam:Euphorbiaceae) were evaluated for hepatoprotective activity by carbon tetrachloride-induced liver damage in rats.The degree of protection was measured by using biochemical parameters such as serum glutamate oxalate transaminase(SGOT/ AST),serum glutamate pyruvate transaminase(SCPT/ALT),alkaline phosphatase(ALP) and total bilirubin.The in vitro antioxidant activity of the extract was also evaluated by the I,I-diphenyl 2-picrylhydrazyl(DPPH) free radical scavenging assay.The extract was subjected to preliminary phytoehemical screening.Results:The ethyl acetate and chloroform fractions,at a dose of 300 mg/kg,produced significant(P【0.05) hepatoprolection by decreasing the activities of the serum enzymes and bilirubin while there were marked scavenging of the DPPH free radicals by the fractions.The effects were comparable to those of the standard drugs used for the respective experiments,silymarin and ascorbic acid.Alkaloids,flavonoids,saponins and tannins were delected in the phylochemical screening.Conclusion:From this study,it was concluded that the plant of A.cordifolia possesses hepatoprotective as well as antioxidant activities and these activities reside mainly in the ethyl acetate and acetone fractions of methanol leaf extract.展开更多
AIM： To investigate the effects of Reishi mushroom, Ganoderma lucidum extract （GLE）, on liver fibrosis induced by carbon tetrachloride （CCl4） in rats. METHODS： Rat hepatic fibrosis was induced by CCl4. Forty Wis...AIM： To investigate the effects of Reishi mushroom, Ganoderma lucidum extract （GLE）, on liver fibrosis induced by carbon tetrachloride （CCl4） in rats. METHODS： Rat hepatic fibrosis was induced by CCl4. Forty Wistar rats were divided randomly into 4 groups： control, CCl4, and two GLE groups. Except for rats in control group, all rats were administered orally with CCl4 （20%, 0.2 mL/100 g body weight） twice a week for 8 weeks. Rats in GLE groups were treated daily with GLE （1 600 or 600 mg/kg） via gastrogavage throughout the whole experimental period. Liver function parameters, such as ALT, AST, albumin, and albumin/globulin （A/G） ratio, spleen weight and hepatic amounts of protein, malondiladehyde （MDA） and hydroxyproline （HP） were determined. Histochemical staining of Sirius red was performed. Expression of transforming growth factor β1 （TGF-β1）, methionine adenosyltransferase （MAT1） 1A and MAT2A mRNA were detected by using RT-PCR. RESULTS： CCl4 caused liver fibrosis, featuring increase in plasma transaminases, hepatic MDA and HP contents, and spleen weight; and decrease in plasma albumin, A/G ratio and hepatic protein level. Compared with CCl4 group, GLE （600, 1 600 mg/kg） treatment significantly increased plasma albumin level and A/G ratio （P〈0.05） and reduced the hepatic HP content （P〈0.01）. GLE （1 600 mg/kg） treatment markedly decreased the activities of transaminases （P〈 0.05）, spleen weight （P〈 0.05） and hepatic MDA content （P〈0.05）; but increased hepatic protein level （P〈0.05）. Liver histology in the GLE （1 600 mg/kg）-treated rats was also improved （P〈0.01）. RT-PCR analysis showed that GLE treatment decreased the expression of TGF-β1 （P〈 0.05-0.001） and changed the expression of MAT1A （P〈0.05-0.01） and MAT2A （P〈 0.05-0.001）. CONCLUSION： Oral administration of GLE significantly reduces CCl4-induced hepatic fibrosis in rats, probably by exerting a protective effect against hepatocellular necrosis by its free-radical scavenging ability.展开更多
AIM： To investigate the possible mechanism of the protective effects of a bioactive fraction, Ganoderma lucidum proteoglycan （GLPG）isolated from Ganoderma luddum mycelia, against carbon tetrachloride-induced liver ...AIM： To investigate the possible mechanism of the protective effects of a bioactive fraction, Ganoderma lucidum proteoglycan （GLPG）isolated from Ganoderma luddum mycelia, against carbon tetrachloride-induced liver injury. METHODS： A liver injury model was induced by carbon tetrachloride. Cytotoxicity was measured by MTY assay. The activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined with an automatic multifunction-biochemical analyzer and the levels of superoxide dismutase （SOD） and TNF-α were determined following the instructions of SOD kit and TNF radioimmunoassay kit. Uver sections were stained with hematoxylin and eosin （H＆E） for histological evaluation and examined under light microscope. RESULTS： We found that GLPG can alleviate the L-02 liver cells injury induced by carbon tetrachloride （CCh） through the measurements of ALT and AST activities and the administration of GLPG to L-02 cells did not display any toxicity. Furthermore, histological analysis of mice liver injury induced by CCh with or without GLPG pretreatment indicated that GLPG can significantly suppress the toxicity induced by CCh in mice liver. We also found that GLPG reduced TNF-α level induced by CCh in the plasma of mice, whereas increased SOD activity in the rat serum. CONCLUSION： GLPG has hepatic protective activity against CCl4 induced injury both in vitro and in vivo. The possible antihepatotoxic mechanisms may be related to the suppression of TNF-α level and the free radical scavenging activity.展开更多
AIM： To evaluate the hepatoprotective roles of （Z）- 5-（4-methoxybenzylidene）thiazolidine-2,4-dione （SKLB010） against carbon tetrachloride （CCI4）-induced acute and chronic liver injury and its underlying mecha...AIM： To evaluate the hepatoprotective roles of （Z）- 5-（4-methoxybenzylidene）thiazolidine-2,4-dione （SKLB010） against carbon tetrachloride （CCI4）-induced acute and chronic liver injury and its underlying mecha- nisms of action.展开更多
To explore the protective effect of extract powder of turmeric on carbon tetrachloride （CCl4）-induced acute hepatic injury, the mice were administrated with extract powder of turmeric with different doses （50, 100,...To explore the protective effect of extract powder of turmeric on carbon tetrachloride （CCl4）-induced acute hepatic injury, the mice were administrated with extract powder of turmeric with different doses （50, 100, 200 mg/kg） for 7 d. Then the mice were treated with 0.12% CCl4 by intraperitoneal injection. The levels of ALT, AST in serum and activities of SOD, CAT, MDA, GSH-Px in liver tissue were detected and the liver lesions were examined. The results showed that the activities of ALT, AST and the level of MDA in extract powder of turmeric group were signif- icantly decreased, and the activities of SOD, CAT, GSH-Px were significantly increased, and liver pathology were improved compared with the injured group （P〈 0.05 or P〈0.01）. It indicated that the extract powder of turmeric had significant protective effect against CCl4 induced acute hepatic injury in mice.展开更多
AIM： To evaluate the protective effect of 2′-p-hydroxy benzoylmussaenosidic acid [negundoside （NG）, against carbon tetrachloride （CCl4）-induced toxicity in HUH-7 cel Is.METHODS： CCI4 is a well characterized hep...AIM： To evaluate the protective effect of 2′-p-hydroxy benzoylmussaenosidic acid [negundoside （NG）, against carbon tetrachloride （CCl4）-induced toxicity in HUH-7 cel Is.METHODS： CCI4 is a well characterized hepatotoxin, and inducer of cytochrome P450 2E1 （CYP2E1）-mediated oxidative stress. In addition, lipid peroxidation and accumulation of intracellular calcium are important steps in the pathway involved in CCl4 toxicity. Liver cells （HUH-7） were treated with CCI4, and the mechanism of the cytoprotective effect of NG was assessed. Silymarin, a known hepatoprotective drug, was used as control. RESULTS： NG protected HUH-7 cells against CCl4 toxicity and loss of viability without modulating CYP2E1 activity. Prevention of CCl4 toxicity was associated with a reduction in oxidative damage as reflected by decreased generation of reactive oxygen species （ROS）, a decrease in lipid peroxidation and accumulation of intracellular Ca^2＋ levels and maintenance of intracellular glutathione homeostasis. Decreased mitochondrial membrane potential （MMP）, induction of caspases mediated DNA fragmentation and cell cycle arrest, as a result of CCl4 treatment, were also blocked by NG. The protection afforded by NG seemed to be mediated by activation of cyclic adenosine monophosphate （cAMP） synthesis and inhibition of phospholipases （cPLA2）. CONCLUSION： NG exerts a protective effect on CYP2E1-dependent CCl4 toxicity via inhibition of lipid peroxidation, followed by an improved intracellular calcium homeostasis and inhibition of Ca^2＋-dependent proteases.展开更多
By comparing the testing data of the hydrochemistry components and organic pollution of karst water sample in Jinan with large amount of historical data, the author finds the long-existing problem of carbon tetrachlor...By comparing the testing data of the hydrochemistry components and organic pollution of karst water sample in Jinan with large amount of historical data, the author finds the long-existing problem of carbon tetrachloride pollution and the great change of hydrochemical characteristics of karst water in eastern suburbs of Jinan. Since karst water is the main water-supply source in eastern suburbs of Jinan, these problems have greatly affected the safety of water supply. Based on the analysis of hydrogeological condition in eastern suburbs of Jinan, this thesis discusses the causes of carbon tetrachloride pollution and hydrochemical variation with hydrogeochemical theories so as to protect the precious karst groundwater and Jinan spring water. It is found that through research and analysis that there are mainly two causes of carbon tetrachloride pollution and hydrochemical variation: the vulnerability of karst water in this area; the other being the serious pollution in this area caused by remaining pollution sources of the last century.展开更多
The formation of·CCl3 radicals in liver nuclei was suggested by spin trapping of them with N-t-butyl-α-phenylnitrone followed by GC/MS detection of the resulting adduct. Comparison of its formation in microsomal...The formation of·CCl3 radicals in liver nuclei was suggested by spin trapping of them with N-t-butyl-α-phenylnitrone followed by GC/MS detection of the resulting adduct. Comparison of its formation in microsomal biotransformation of CCl4 was made. In aerobic nuclear activation mixtures containing NADPH and CCl4, significant decrease in the arachidonic acid content of nuclear lipids was observed (27. 8%, compared to control), the intensity of this decrease was lower than that occurring in the corresponding microsomal incubation mixtures (29.1%). Significant decreases in arachidonic acid content of nuclear and endoplasmic reticulum lipids were also observed in animals at 6 hours of poisoning with the haloalkane. During aerobic nuclear metabolism of CCl4 or CBrCl3, cholesterol oxidation products were detected: a ketocholesterol, an epoxide like structure and 7-ketocholesterol. Nuclear protein carbonyl formation was not promoted during nuclear CCl4 biotransformation. NADPH by itself may lead to protein carbonyl formation during prolonged periods of incubation. CBrCl3 in contrast, led to decreased protein carbonyl formation. No increase in nuclear protein carbonyl formation was observed in CCl4 intoxicated animals during periods of time between 1 to 6 hours after treatment. The results indicate that during nuclear biotransformation of CCl4 or CBrCl3 reactive free radicals, PUFA degradation, reactive aldehydes and cholesterol oxidation products are formed, nearby DNA and regulatory proteins.展开更多
AIM： To study the effect of WeiJia on chronic liver injury using carbon tetrachloride （CCh） induced liver injury animal model. METHODS： Wistar rats weighing 180-220g were randomly divided into three groups： norma...AIM： To study the effect of WeiJia on chronic liver injury using carbon tetrachloride （CCh） induced liver injury animal model. METHODS： Wistar rats weighing 180-220g were randomly divided into three groups： normal control group （Group A）, CCh induced liver injury control group （Group B） and CCI4 induction with WeiJia treatment group （Group C）. Each group consisted of 14 rats. Liver damage and fibrosis was induced by subcutaneous injection with 40% CCh in olive oil at 3 mL/kg body weight twice a week for eight weeks for Groups B and C rats whereas olive oil was used for Group A rats. Starting from the third week, Group C rats also received daily intraperitoneal injection of Wei.lia at a dose of 1.25 μg/kg body weight. Animals were sacrificed at the fifth week （4 male, 3 female）, and eighth week （4 male, 3 female） respectively. Degree of fibrosis were measured and serological markers for liver fibrosis and function including hyaluronic acid （HA）, type Ⅳ collagen （CIV）, γ-glutamyl transferase （γ-GT）, alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined. Alpha smooth muscle actin （α-SMA） and proliferating cell nuclear antigen （PCNA） immunohistochemistry were also performed. RESULTS： CCl4 induction led to the damage of liver and development of fibrosis in Group B and Group C rats when compared to Group A rats. The treatment of WeiJia in Group C rats could reduce the fibrosis condition significantly compared to Group B rats. The effect could be observed after three weeks of treatment and was more obvious after eight weeks of treatment. Serum HA, CIV,ALT, AST and γ-GT levels after eight weeks of treatment for Group C rats were 58±22 μg/L （P〈0.01）, 57±21 μg/L （P〈0.01）, 47±10 U/L （P〈0.01）, 139±13 U/L （P〈0.05） and 52±21 U/L （P〉0.05） respectively, similar to normal control group （Group A）, but significantly different from CCh induced liver injury control group （Group B）. An increase in PCNA and decrease in α-SMA expression level was also observed. CONCLUSION： WeiJia could improve liver function and reduce liver fibrosis which might be through the inhibition of stellate cell activity.展开更多
The protective effect of biphenyl dimethyl dicarboxylate (DDB) on chemically induced damages was studied in isolated suspended rat hepatocytes. The experimental results showed that DDB (200μg/106 cells) efficiently p...The protective effect of biphenyl dimethyl dicarboxylate (DDB) on chemically induced damages was studied in isolated suspended rat hepatocytes. The experimental results showed that DDB (200μg/106 cells) efficiently protected the hepatocytes against carbon tetrachloride (CC14 10 mrnol.L-1) and D-galactosamine (1 mmol.L-1) induced damages. Membranal lipid peroxidation (malondialdehyde, MDA formation) and glutamic pyruvic transaminase (GPT) release from the hepatocytes were markedly decreased. The damage of the cell surfaces of the hepatocytes were also reduced as seen under a scanning electron microscope (SEM). Pretreatment with DDB (300 mg-kg-1) orally ameliorated the reduction of liver glycogen and blood glucose caused by ip injection of D-galactosamine (800 mg-kg-1) in mice. When normal rats were given DDB 300 mg-kg-1 once daily for 10 d, the free ribosomal protein and RNA in the liver increased significantly. These results indicate that DDB is of beneficial effects on both damaged and normal hepatocytes.展开更多
The pressure-induced molecular dissociation as one of the fundamental problems in physical sciences has aroused many theoretical and experimental studies. Here, using a newly developed particle swarm optimization algo...The pressure-induced molecular dissociation as one of the fundamental problems in physical sciences has aroused many theoretical and experimental studies. Here, using a newly developed particle swarm optimization algorithm, we investigate the high-pressure-induced molecular dissociation. The results show that the carbon tetrachloride （CC14） is unstable and dissociates into C2C16 and C12 under approximately 120 GPa and more. The dissociation is confirmed by the lattice dynamic calculations and electronic structure of the Pa3 structure with pressure evolution. The dissociation pressure is far larger than that in the case of high temperature, indicating that the temperature effectively reduces the activation barrier of the dissociation reaction of CC14. This research improves the understanding of the dissociation reactions of CC14 and other halogen compounds under high pressures.展开更多
基金Supported by The Panzhihua Science and Technology Planning Project of China,No.2023ZD-S-57.
文摘BACKGROUND C23,an oligo-peptide derived from cold-inducible RNA-binding protein(CIRP),has been reported to inhibit tissue inflammation,apoptosis and fibrosis by binding to the CIRP receptor;however,there are few reports on its role in liver fibrosis and the underlying mechanism is unknown.AIM To explore whether C23 plays a significant role in carbon tetrachloride(CCl4)-induced liver fibrosis.METHODS CCl4 was injected for 6 weeks to induce liver fibrosis and C23 was used beginning in the second week.Masson and Sirius red staining were used to examine changes in fiber levels.Inflammatory factors in the liver were detected and changes inα-smooth muscle actin(α-SMA)and collagen I expression were detected via immu-nohistochemical staining to evaluate the activation of hematopoietic stellate cells(HSCs).Western blotting was used to detect the activation status of the trans-forming growth factor-beta(TGF-β)/Smad3 axis after C23 treatment.RESULTS CCl4 successfully induced liver fibrosis in mice,while tumor necrosis factor-alpha(TNF-α),IL(interleukin)-1β,and IL-6 levels increased significantly and the IL-10 level decreased significantly.Interestingly,C23 inhibited this process.On the other hand,C23 significantly inhibited the activation of HSCs induced by CCl4,which inhibited the expression ofα-SMA and the synthesis of collagen I.In terms of mechanism,C23 can block Smad3 phosphorylation significantly and inhibits INTRODUCTION At present there is no specific and effective drug for treating liver fibrosis caused by acute or chronic injury.Although preclinical research has made breakthroughs,their suitability as clinical treatments is still unknown.The activation of hepatic stellate cells(HSCs)caused by chronic inflammation is a key process in the development of liver fibrosis and activated HSCs expressα-smooth muscle actin(α-SMA)and transdifferentiate into myofibroblasts with proliferation,migration and secretion abilities,synthesizing the extracellular matrix to deposit in the hepatocyte space and subse-quently forming liver fibrosis[1].Although therapeutic strategies have improved due to past few efforts there is no ideal treatment for hepatic fibrosis[2].Extracellular cold inducible RNA binding protein(CIRP)has been shown to play a role in various acute and chronic inflammatory diseases by promoting tissue inflammation and apoptosis and inducing fibrosis through its receptor Toll-like receptor 4(TLR4)[3].C23 is a recognized competitive inhibitor of CIRP that can competitively bind to CIRP receptors and reduce tissue damage in inflammatory diseases[4].C23 has been shown to significantly reduce serum tumor necrosis factor-alpha(TNF-α),IL(interleukin)-6 and IL-1βlevels.In addition,it can reduce tissue TLR4,TNF-α,IL-6 and IL-1βlevels and inhibit the colocalization of CIRP and TLR4,which plays a significant role in systemic inflammation[5].Re-search has shown that CIRP induces the inflammatory phenotype of lung fibroblasts in a TLR4-dependent manner[6].On the other hand,CIRP is associated with markers of fibrosis andα-SMA is significantly positively correlated with CIRP.Cirp-/-mice exhibit attenuated expression ofα-SMA and collagen(COL1A1 and COL3A1),decreased hydroxyproline content,decreased histological fibrosis scores,and improved pulmonary hypertension[7].C23 inhibited the release of TNF-α,the degradation of IκB and the nuclear translocation of NF-κB in CIRP-stimulated macrophages in a dose-dependent manner and C23 treatment significantly increased the serum levels of lactic dehydrogenase,alanine ami-notransferase,IL-6,TNF-αand IL-1βin septic CLP mice[8].Based on previous research we hypothesized that C23 might alleviate liver fibrosis by inhibiting acute and chronic inflammation.As a selective hepatotoxic chemical carbon tetrachloride(CCl4).can induce inflammation and activate HSCs,promoting liver fibrosis.This study reveals the role and mechanism of C23 in CCl4-induced liver fibrosis in mice.at room temperature for 30 minutes.The gray value of each group was calculated after chemiluminescence.
基金Supported by National Key Technology R&D Program,No.2012BAI30B02
文摘AIM To investigate the protective effects of Foeniculum vulgare root bark (FVRB), a traditional Uyghur medicine, against carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice. METHODS Mice were randomly divided into eight groups (n = 20 each). Except for the normal control group, mice in the rest groups were intraperitoneally injected (i.p.) with 0.1% CCl4-olive oil mixture at 10 mL/kg twice a week to induce liver fibrosis. After 4 wk, mice were treated concurrently with the 70% ethanol extract of FVRB (88, 176, 352 and 704 mg/kg, respectively) daily by oral gavage for 4 wk to evaluate its protective effects. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), hexadecenoic acid (HA), laminin (LN), glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) in liver tissues were measured. Hematoxylin-eosin (H and E) staining and Masson trichrome (MT) staining were performed to assess histopathological changes in the liver. The expression of transforming growth factor beta 1 (TGF-beta 1), matrix metalloprotein 9 (MMP-9) and metallopeptidase inhibitor 1 (TIMP-1) was detected by immunohistochemical analysis. Additionally, TGF-beta 1 and alpha-smooth muscle actin (alpha-SMA) protein expression was measured by Western blot. RESULTS A significant reduction in serum levels of AST, ALT, TG, HA and LN was observed in the FVRB-treated groups, suggesting that FVRB displayed hepatoprotective effects. Also, the depletion of GSH, SOD, and MDA accumulation in liver tissues was suppressed by FVRB. The expression of TGF-beta 1, MMP-9 and TIMP-1 determined by immunohistochemistry was markedly reduced in a dose-dependent manner by FVRB treatment. Furthermore, protective effects of FVRB against CCl4-induced liver injury were confirmed by histopathological studies. Protein expression of TGF-beta 1 and alpha-SMA detected by Western blot was decreased by FVRB treatment. CONCLUSION Our results indicate that FVRB may be a promising agent against hepatic fibrosis and its possible mechanisms are inhibiting lipid peroxidation and reducing collagen formation in liver tissue of liver fibrosis mice.
基金Supported by The Major Project of Applied Basic Research Plan of the Scientific and Technological Department of Tianjin,No.06YFJZJC02900
文摘AIM:To explore the anti-fibrotic effect of Haobie Yangyin Ruanjian Decoction(HYRD)on CCl4-induced hepatic fibrosis in rats and its modulation on the transforming growth factor(TGF)β-Smad signaling pathway.METHODS:Fifty-six healthy Wistar rats were randomly divided into five groups:normal control group(n=6),CCl4-induced hepatic fibrosis group(n=14) and three treatment groups(the treated rats received HYRD via oral administration at daily dosages of 8.2,2.5 and 0.82 g/kg,respectively)of HYRD(n=12,respectively).Experimental hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride solution(CCl4 dissolved in peanut oil,4:6,V/V)with 0.5 mL/100 g body weight for the first time,and then 0.3 mL/100 g body weight twice a week for 8 wk.In the former 2 wk,rats were raised by feedstuffⅠ(80% corn meal,20%lard,0.5%cholesterol).After 2 wk,they were raised by feedstuffⅡ(corn meal and 0.5% cholesterol).Except for the control group,30%alcohol solution was given orally to each rat every other day from the beginning,1 mL for each rat.Liver function parameters and hepatic hydroxyproline content were detected by chromatometry.Serum levels of hyaluronic acid(HA),typeⅣcollagen(CIV),typeⅢprecollagen(PCⅢ)and laminin(LN)were assayed with radioimmunoassay.Deposition of collagen was observed with hematoxylin-eosin staining and collagen staining.Gene expression of TGFβ1 and Smad3 were detected with real-time reverse transcriptase-polymerase chain reaction and Western blotting,respectively.RESULTS:The serum levels of alanine transaminase and aspartate transaminase were increased in the model group compared with the control group(P<0.01),and they were decreased in the three treatment groups compared with the model group.The serum levels of total protein and albumin were decreased in the model group and increased in the three treatment groups.The hepatic hydroxyproline content and serum levels of PCⅢ,HA,LN and CIV were markedly increased in the model group compared with the control group,and decreased in the treatment groups.The gene expression of TGFβ1 and Smad3 was enhanced in the model group compared with the control group,and HYRD could down regulate their expression.CONCLUSION:HYRD can inhibit hepatic fibrosis induced by CCl4 in rats,which is probably associated with its down-regulation on fibrogenic signal transduction of TGFβ-Smad pathway.
基金Supported by The Natural Science Foundation of China,Grants No.30801005,No.81273199and No.81270513the Project of Science and Development of Jilin Province(to Liu ZH)
文摘AIM: To investigate the expression and role of activin A in a mouse model of acute chemical liver injury. METHODS: Acute liver injury in C57BL/6 male mice was induced by intraperitoneal injection with carbon tetrachloride (CCl4 ) (0.5 mL/kg, body weight) dissolved in olive oil (1:19 v/v). Mice were sacrificed 1, 3, 5 and 7 d after the treatment. The levels of alanine aminotrans-ferase (ALT) and aspartate aminotransferase (AST) in serum were examined and pathological changes of liver observed by hematoxylin and eosin staining to evaluate the liver injury. Activin A protein levels in serum and hepatic tissue homogenate of mice were detected by enzyme-linked immunosorbent assay, and the expres-sion pattern of activin A protein in livers of mice was examined by immunohistochemistry. Activin type Ⅱ A receptor (ActRⅡA) and Smad3 expressions in the liver were analyzed by real-time quantitative reverse transcription-polymerase chain reaction. In order to further investigate the role of activin A, we also utilized activin A blocking experiment by anti-activin A antibody (500 μg/kg, body weight) injection into mouse tail vein. RESULTS: In CCl4-treated mice, serum ALT and AST levels were significantly increased, compared with that in control mice (P<0.01). Furthermore, the serious necrosis was observed around hepatic portal areas in CCl4-treated mice. Simultaneously, activin A levels in serum and hepatic tissue homogenate of mice treated with CCl4 for 1, 3 and 5 d increased significantly, com-pared with that in control mice (P<0.01). Activin A protein expression in hepatocytes not within the ne-crotic area was also upregulated in mice following CCl4 treatment. Not only activin A, but also ActRⅡA and activin signaling molecule Smad3 mRNA expressions in injury liver induced by CCl4 were significantly higher than that in control liver. In addition, levels of serum ALT and AST in CCl4-treated mice were significantly decreased by injection of anti-activin A antibody to block endogenous activin A action, compared with that in CCl4-treated mice by injection of immunoglobulin G instead of anti-activin A antibody (P<0.01), and the severity of liver injury was also reduced remarkably. CONCLUSION: These data show that activin A is in-volved in CCl4-induced acute liver injury. Blocking ac-tivin A actions may be a therapeutic approach for acute liver injury.
文摘Objective:To investigate the hepatoprotective activity of Averroha carambola fruit extract against carbon tetrachloride induced hepatic injury.Methods:Hepatotoxicity was induced on albino mice by intraperitoneal administration of CCl<sub>4</sub>.half an hour after the administration of the last dose of the extract of Averroha carambola fruit.Aqueous extract of the fruit of Averroha carambola was administered at a dose of 0.9 g/kg body weight once daily for seven days.The hepatic injury and its prevention was assessed by the estimation of serum activities of alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,alkaline phosphates（ALP）,glutathione level and histopathological studies of liver.Results:Pre-treatment of mice with the fruit extract of Averrhoea carambola significantly reduced serum levels of ALT,AST and ALP enzyme and significantly increased the liver reduced glutathione levels 24 h after the administration of carbon tetrachloride.A marked improvement in the enzyme activities and the liver reduced glulathione level was observed in the pre-treated mice 4 days after the administration of carbon tetrachloride. Histopathological studies provided supportive evidence for the biochemical analvsis. Conclusions:The aqueous extract of the fruit of Averrhoea carambola has hepatoprotective effect against carbon tetrachloride induced liver damage in mice.
文摘AIM： To develop a simplified and quick protocol to induce cirrhosis and standardize models of partial liver resection in rats. METHODS： In Fischer F344 rats two modified protocols of phenobarbital-carbon tetrachloride （CCl4） （dilution 50%） gavage to induce cirrhosis （frequency adjusted according to weight, but each subsequent dose was systematically administered） were tested, i.e. the rapid and slow protocols. Prothrombin time （PT） and total bilirubin （TB） were also evaluated. Animals from the rapid group underwent 15% hepatectomy and animals from the slow group underwent 70% hepatectomy. RESULTS： Rapid protocol： This corresponded to 1 gavage/4 d over 6 wk （mortality 30%）. Mean PT was 35.2 ±2.8 s （normal： ld.5 s）, and mean TB was 1.8 ± 0.2 mg/dL （normal： 0.1 mg/dL）. Slow protocol： This cop responded to 1 gavage/6 d over 9 wk （mortality 10%）. Mean PT was 11.8 ± 0.2 s （normal： 14.5 s）, and mean TB was 0.4 ± 0.04 mg/dL （normal： 0.1 mg/dL）. Pathological analyses were performed in both protocols which showed persistent cirrhosis at 3 mo. Rat mortality in the rapid garage group who underwent 15% hepatectomy and in the slow garage group who underwent 70% hepatectomy was 50% and 70%, respectively, CONCLUSION： Our modified model is a simplified method to induce cirrhosis which is rapid （6 to 9 wk）, efficient and stable up to 3 mo. Using this method, ＂Child Pugh A＂ or ＂Child Pugh BC＂ cirrhotic rats were obtained. Our models of cirrhosis and hepatectomy can be used in various situations focusing on postoperative survival.
基金Project(2004C33068) supported by the Science and Technology Programs of Zhejiang Province,ChinaProject(20100933B17) supported by the Social Development and Science Research Program of Hangzhou,China
文摘The isotherm,mechanism and kinetics of carbon tetrachloride(CT) adsorption by polyacrylonitrile-based activated carbon fiber(PAN-ACF) were investigated in batch reactors and a continuous flow reactor,and the regeneration of PAN-ACF was also studied.Freundlich and Dubinin-Radushkevich(D-R) adsorption equations can well describe the adsorption isotherm.CT is mainly adsorbed on the exterior surface of PAN-ACF with low boundary layer effect and rate-controlling step of intra-particle diffusion.The adsorption dynamics in the batch reactor well fits with the pseudo-first-order model,and the breakthrough curves in the continuous flow reactor can be well described by the Yoon-Nelson model.The ACF can be recycled through thermal regeneration,whereas the adsorption capacity decreases from 7.87 to 4.98 mg/g after the fourth regeneration.78%-94%of CT can be removed from the wastewater of a fluorine chemical plant on a pilot scale,which confirms the efficacy of ACF under industrial conditions.The results indicate that PAN-ACF is applicable to CT removal from wastewater.
基金supported in part by Hibah Competition Grants Research(Research No.UGM/FA/754.a/M/05/01) from the Ministry of National Education of Indonesia
文摘Objective:To investigate the hepatoproteetivc ami antioxidant activity of pentagamavunon-0(PGV-0) against CCl-4-induced hepatic injury in rats.Methods:The groups of animals were administered with PGV-0 at die doses 2.5.5,10,and 20 mg/kg b.w.,p.o.once in a day for 6 days and at day 7 the animals were administrated with carbon tetrachloride(CClj)(20%,2 ml/kg b.w.in liquid paraffin dp.).The effect of PGV-0 on serum transaminase(SGPT),alkaline phosphates(ALP and total bilirubin were determined in CCl-4-indueed hepatotoxicity in rats.Further,the effects of PGV-0 on glutathione(GSU) content,cutalase(CAT) and NO free radical scavenging activity also were investigated.Results:The results demonstrated that PCV-0 significantly reduced the activity of SGPT,serum ALP and total bilirubin in CCl-4 induced rat hepatotoxicity.PGV-0 has effect on the antioxidant and free radical defense system.It prevented the depletion level of GSH and decrease activity of CAT in CCl-4-induced liver injury in rats.PCV-0 also demonstrated the free radical scavenger effects on NO free radical scavenging activity with ES value of 32.32μM. Convulsion:All of our findings suggests that PGV-0 could protect the liver cells from CCl-4- induced liver damages and the mechanism may through the antioxidative effect of PGV-0 to prevent the accumulation of free radicals and protect the liver damage.
文摘Objective:To investigate the hepatoprotective and antioxidant activities of Alchornea cordifolia (A.cordifolia) leaf extract.Methods:Various solvent fractions of the methanol extract of the leaf of the plant.4.cordifolia Mull.Arg(Fam:Euphorbiaceae) were evaluated for hepatoprotective activity by carbon tetrachloride-induced liver damage in rats.The degree of protection was measured by using biochemical parameters such as serum glutamate oxalate transaminase(SGOT/ AST),serum glutamate pyruvate transaminase(SCPT/ALT),alkaline phosphatase(ALP) and total bilirubin.The in vitro antioxidant activity of the extract was also evaluated by the I,I-diphenyl 2-picrylhydrazyl(DPPH) free radical scavenging assay.The extract was subjected to preliminary phytoehemical screening.Results:The ethyl acetate and chloroform fractions,at a dose of 300 mg/kg,produced significant(P【0.05) hepatoprolection by decreasing the activities of the serum enzymes and bilirubin while there were marked scavenging of the DPPH free radicals by the fractions.The effects were comparable to those of the standard drugs used for the respective experiments,silymarin and ascorbic acid.Alkaloids,flavonoids,saponins and tannins were delected in the phylochemical screening.Conclusion:From this study,it was concluded that the plant of A.cordifolia possesses hepatoprotective as well as antioxidant activities and these activities reside mainly in the ethyl acetate and acetone fractions of methanol leaf extract.
文摘AIM： To investigate the effects of Reishi mushroom, Ganoderma lucidum extract （GLE）, on liver fibrosis induced by carbon tetrachloride （CCl4） in rats. METHODS： Rat hepatic fibrosis was induced by CCl4. Forty Wistar rats were divided randomly into 4 groups： control, CCl4, and two GLE groups. Except for rats in control group, all rats were administered orally with CCl4 （20%, 0.2 mL/100 g body weight） twice a week for 8 weeks. Rats in GLE groups were treated daily with GLE （1 600 or 600 mg/kg） via gastrogavage throughout the whole experimental period. Liver function parameters, such as ALT, AST, albumin, and albumin/globulin （A/G） ratio, spleen weight and hepatic amounts of protein, malondiladehyde （MDA） and hydroxyproline （HP） were determined. Histochemical staining of Sirius red was performed. Expression of transforming growth factor β1 （TGF-β1）, methionine adenosyltransferase （MAT1） 1A and MAT2A mRNA were detected by using RT-PCR. RESULTS： CCl4 caused liver fibrosis, featuring increase in plasma transaminases, hepatic MDA and HP contents, and spleen weight; and decrease in plasma albumin, A/G ratio and hepatic protein level. Compared with CCl4 group, GLE （600, 1 600 mg/kg） treatment significantly increased plasma albumin level and A/G ratio （P〈0.05） and reduced the hepatic HP content （P〈0.01）. GLE （1 600 mg/kg） treatment markedly decreased the activities of transaminases （P〈 0.05）, spleen weight （P〈 0.05） and hepatic MDA content （P〈0.05）; but increased hepatic protein level （P〈0.05）. Liver histology in the GLE （1 600 mg/kg）-treated rats was also improved （P〈0.01）. RT-PCR analysis showed that GLE treatment decreased the expression of TGF-β1 （P〈 0.05-0.001） and changed the expression of MAT1A （P〈0.05-0.01） and MAT2A （P〈 0.05-0.001）. CONCLUSION： Oral administration of GLE significantly reduces CCl4-induced hepatic fibrosis in rats, probably by exerting a protective effect against hepatocellular necrosis by its free-radical scavenging ability.
基金Supported by a grant from the Institute of Virology, College of Life Sciences, Wuhan University
文摘AIM： To investigate the possible mechanism of the protective effects of a bioactive fraction, Ganoderma lucidum proteoglycan （GLPG）isolated from Ganoderma luddum mycelia, against carbon tetrachloride-induced liver injury. METHODS： A liver injury model was induced by carbon tetrachloride. Cytotoxicity was measured by MTY assay. The activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined with an automatic multifunction-biochemical analyzer and the levels of superoxide dismutase （SOD） and TNF-α were determined following the instructions of SOD kit and TNF radioimmunoassay kit. Uver sections were stained with hematoxylin and eosin （H＆E） for histological evaluation and examined under light microscope. RESULTS： We found that GLPG can alleviate the L-02 liver cells injury induced by carbon tetrachloride （CCh） through the measurements of ALT and AST activities and the administration of GLPG to L-02 cells did not display any toxicity. Furthermore, histological analysis of mice liver injury induced by CCh with or without GLPG pretreatment indicated that GLPG can significantly suppress the toxicity induced by CCh in mice liver. We also found that GLPG reduced TNF-α level induced by CCh in the plasma of mice, whereas increased SOD activity in the rat serum. CONCLUSION： GLPG has hepatic protective activity against CCl4 induced injury both in vitro and in vivo. The possible antihepatotoxic mechanisms may be related to the suppression of TNF-α level and the free radical scavenging activity.
基金Supported by National Natural Science Foundation of China and National Key Technologies R and D Program of the 11th five-year plan,No.2009ZX09501-015
文摘AIM： To evaluate the hepatoprotective roles of （Z）- 5-（4-methoxybenzylidene）thiazolidine-2,4-dione （SKLB010） against carbon tetrachloride （CCI4）-induced acute and chronic liver injury and its underlying mecha- nisms of action.
基金Supported by the Scientific and Technological Innovation Project of Wuhan Academy of Agricultural Science&Technology(CX201417)~~
文摘To explore the protective effect of extract powder of turmeric on carbon tetrachloride （CCl4）-induced acute hepatic injury, the mice were administrated with extract powder of turmeric with different doses （50, 100, 200 mg/kg） for 7 d. Then the mice were treated with 0.12% CCl4 by intraperitoneal injection. The levels of ALT, AST in serum and activities of SOD, CAT, MDA, GSH-Px in liver tissue were detected and the liver lesions were examined. The results showed that the activities of ALT, AST and the level of MDA in extract powder of turmeric group were signif- icantly decreased, and the activities of SOD, CAT, GSH-Px were significantly increased, and liver pathology were improved compared with the injured group （P〈 0.05 or P〈0.01）. It indicated that the extract powder of turmeric had significant protective effect against CCl4 induced acute hepatic injury in mice.
基金Indian Institute of Integrative Medicine, Council of Scientific and Industrial Research
文摘AIM： To evaluate the protective effect of 2′-p-hydroxy benzoylmussaenosidic acid [negundoside （NG）, against carbon tetrachloride （CCl4）-induced toxicity in HUH-7 cel Is.METHODS： CCI4 is a well characterized hepatotoxin, and inducer of cytochrome P450 2E1 （CYP2E1）-mediated oxidative stress. In addition, lipid peroxidation and accumulation of intracellular calcium are important steps in the pathway involved in CCl4 toxicity. Liver cells （HUH-7） were treated with CCI4, and the mechanism of the cytoprotective effect of NG was assessed. Silymarin, a known hepatoprotective drug, was used as control. RESULTS： NG protected HUH-7 cells against CCl4 toxicity and loss of viability without modulating CYP2E1 activity. Prevention of CCl4 toxicity was associated with a reduction in oxidative damage as reflected by decreased generation of reactive oxygen species （ROS）, a decrease in lipid peroxidation and accumulation of intracellular Ca^2＋ levels and maintenance of intracellular glutathione homeostasis. Decreased mitochondrial membrane potential （MMP）, induction of caspases mediated DNA fragmentation and cell cycle arrest, as a result of CCl4 treatment, were also blocked by NG. The protection afforded by NG seemed to be mediated by activation of cyclic adenosine monophosphate （cAMP） synthesis and inhibition of phospholipases （cPLA2）. CONCLUSION： NG exerts a protective effect on CYP2E1-dependent CCl4 toxicity via inhibition of lipid peroxidation, followed by an improved intracellular calcium homeostasis and inhibition of Ca^2＋-dependent proteases.
基金supported by the Key Basic Project of Shandong Province:Jinan Urban Geological Survey-Issued in Shandong(2009)046
文摘By comparing the testing data of the hydrochemistry components and organic pollution of karst water sample in Jinan with large amount of historical data, the author finds the long-existing problem of carbon tetrachloride pollution and the great change of hydrochemical characteristics of karst water in eastern suburbs of Jinan. Since karst water is the main water-supply source in eastern suburbs of Jinan, these problems have greatly affected the safety of water supply. Based on the analysis of hydrogeological condition in eastern suburbs of Jinan, this thesis discusses the causes of carbon tetrachloride pollution and hydrochemical variation with hydrogeochemical theories so as to protect the precious karst groundwater and Jinan spring water. It is found that through research and analysis that there are mainly two causes of carbon tetrachloride pollution and hydrochemical variation: the vulnerability of karst water in this area; the other being the serious pollution in this area caused by remaining pollution sources of the last century.
文摘The formation of·CCl3 radicals in liver nuclei was suggested by spin trapping of them with N-t-butyl-α-phenylnitrone followed by GC/MS detection of the resulting adduct. Comparison of its formation in microsomal biotransformation of CCl4 was made. In aerobic nuclear activation mixtures containing NADPH and CCl4, significant decrease in the arachidonic acid content of nuclear lipids was observed (27. 8%, compared to control), the intensity of this decrease was lower than that occurring in the corresponding microsomal incubation mixtures (29.1%). Significant decreases in arachidonic acid content of nuclear and endoplasmic reticulum lipids were also observed in animals at 6 hours of poisoning with the haloalkane. During aerobic nuclear metabolism of CCl4 or CBrCl3, cholesterol oxidation products were detected: a ketocholesterol, an epoxide like structure and 7-ketocholesterol. Nuclear protein carbonyl formation was not promoted during nuclear CCl4 biotransformation. NADPH by itself may lead to protein carbonyl formation during prolonged periods of incubation. CBrCl3 in contrast, led to decreased protein carbonyl formation. No increase in nuclear protein carbonyl formation was observed in CCl4 intoxicated animals during periods of time between 1 to 6 hours after treatment. The results indicate that during nuclear biotransformation of CCl4 or CBrCl3 reactive free radicals, PUFA degradation, reactive aldehydes and cholesterol oxidation products are formed, nearby DNA and regulatory proteins.
基金Supported by Innovation and Technology Fund of the Hong Kong SAR Government(UIM/101)the National Hi-Tech 863 Program of the Ministry of Science and Technology of China,2003AA2Z2052
文摘AIM： To study the effect of WeiJia on chronic liver injury using carbon tetrachloride （CCh） induced liver injury animal model. METHODS： Wistar rats weighing 180-220g were randomly divided into three groups： normal control group （Group A）, CCh induced liver injury control group （Group B） and CCI4 induction with WeiJia treatment group （Group C）. Each group consisted of 14 rats. Liver damage and fibrosis was induced by subcutaneous injection with 40% CCh in olive oil at 3 mL/kg body weight twice a week for eight weeks for Groups B and C rats whereas olive oil was used for Group A rats. Starting from the third week, Group C rats also received daily intraperitoneal injection of Wei.lia at a dose of 1.25 μg/kg body weight. Animals were sacrificed at the fifth week （4 male, 3 female）, and eighth week （4 male, 3 female） respectively. Degree of fibrosis were measured and serological markers for liver fibrosis and function including hyaluronic acid （HA）, type Ⅳ collagen （CIV）, γ-glutamyl transferase （γ-GT）, alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were determined. Alpha smooth muscle actin （α-SMA） and proliferating cell nuclear antigen （PCNA） immunohistochemistry were also performed. RESULTS： CCl4 induction led to the damage of liver and development of fibrosis in Group B and Group C rats when compared to Group A rats. The treatment of WeiJia in Group C rats could reduce the fibrosis condition significantly compared to Group B rats. The effect could be observed after three weeks of treatment and was more obvious after eight weeks of treatment. Serum HA, CIV,ALT, AST and γ-GT levels after eight weeks of treatment for Group C rats were 58±22 μg/L （P〈0.01）, 57±21 μg/L （P〈0.01）, 47±10 U/L （P〈0.01）, 139±13 U/L （P〈0.05） and 52±21 U/L （P〉0.05） respectively, similar to normal control group （Group A）, but significantly different from CCh induced liver injury control group （Group B）. An increase in PCNA and decrease in α-SMA expression level was also observed. CONCLUSION： WeiJia could improve liver function and reduce liver fibrosis which might be through the inhibition of stellate cell activity.
文摘The protective effect of biphenyl dimethyl dicarboxylate (DDB) on chemically induced damages was studied in isolated suspended rat hepatocytes. The experimental results showed that DDB (200μg/106 cells) efficiently protected the hepatocytes against carbon tetrachloride (CC14 10 mrnol.L-1) and D-galactosamine (1 mmol.L-1) induced damages. Membranal lipid peroxidation (malondialdehyde, MDA formation) and glutamic pyruvic transaminase (GPT) release from the hepatocytes were markedly decreased. The damage of the cell surfaces of the hepatocytes were also reduced as seen under a scanning electron microscope (SEM). Pretreatment with DDB (300 mg-kg-1) orally ameliorated the reduction of liver glycogen and blood glucose caused by ip injection of D-galactosamine (800 mg-kg-1) in mice. When normal rats were given DDB 300 mg-kg-1 once daily for 10 d, the free ribosomal protein and RNA in the liver increased significantly. These results indicate that DDB is of beneficial effects on both damaged and normal hepatocytes.
基金Project supported by the National Natural Science Foundation of China (Grant Nos.10974067 and 11104107)the Program of the Science and Technology Department of Jilin Province,China (Grant Nos.20090534 and 20101508)the China Postdoctoral Science Foundation (Grant No.20110491320)
文摘The pressure-induced molecular dissociation as one of the fundamental problems in physical sciences has aroused many theoretical and experimental studies. Here, using a newly developed particle swarm optimization algorithm, we investigate the high-pressure-induced molecular dissociation. The results show that the carbon tetrachloride （CC14） is unstable and dissociates into C2C16 and C12 under approximately 120 GPa and more. The dissociation is confirmed by the lattice dynamic calculations and electronic structure of the Pa3 structure with pressure evolution. The dissociation pressure is far larger than that in the case of high temperature, indicating that the temperature effectively reduces the activation barrier of the dissociation reaction of CC14. This research improves the understanding of the dissociation reactions of CC14 and other halogen compounds under high pressures.
