|
|
| Cytokine Database |
|
CHEMOKINE (C-C MOTIF) LIGAND 4
LATEST LITERATURE
1: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research, 2010 Jun 24, 273(1-3)
CCL4/MIP-1beta Levels in Tear Fluid and Serum of Patients with Cystic Fibrosis.
[Abstract]Cystic fibrosis (CF) is an autosomal recessive genetic disorder. The disease affects all secretory epithelia including the eye and belongs to the group of ocular surface epithelial diseases, termed keratoconjunctivitis sicca that develop in dry eye. In the pathogenesis of dry eye, inflammation plays a crucial role. The aim of this study was to assess the potential role of MIP-1beta in the pathogenesis of dry eye syndrome in patients with CF. We assayed MIP-1beta levels in tear fluid and serum of 28 patients with CF and 27 controls by ELISA. The ophthalmic examinations including the tests for dry eye were used to study the ocular surface. The tear levels of MIP-1beta in the CF patients were significantly higher than those in the controls. Dry eye syndrome was observed in 10 (36%) CF patients. The tear fluid levels of MIP-1beta were significantly raised in CF patients with dry eye syndrome compared with CF patients without dry eye symptoms. Our results suggest a crucial role of CCL4/MIP-1beta in the development of dry eye syndrome in CF patients and immunopathogenesis of ocular surface changes in this disease. Clarification of the role of CCL4/MIP-1beta in the pathogenesis of ocular findings in CF patients will be useful in establishing immunotherapeutic strategies for this disease.
2: Human & experimental toxicology, 2010 Jun 22, 273(1-3)
Protective effect of Ginkgo biloba exctract on liver damage by a single dose of CCl4 in male rats.
[Abstract]Functional and morphological alterations were generated by p.o. (per os) administration of a single oral dose of carbon tetrachloride (CCl4; 0.125 mL/kg b.w., equivalent to 293 mg/kg) to adult male Wistar rats. CCl4 significantly increased (p < 0.05) the serum activities of alanine aminotransferase (ALT; 7478 +/- 1044%) and aspartate aminotransferase (AST; 6964 +/- 833%), compared to control rats; CCl4 also significantly decreased serum concentration of albumin (23 +/- 5.5%) and increased the concentration of malondialhdeyde (MDA) in liver (300 +/- 33%). Furthermore, CCl4 down-regulated the mRNA steady-state level of tumor necrosis factor alpha(TNF-alpha). CCl4 produced necrosis in the central lobe area, extended to the periphery, nuclear alterations (pycnosis, karyolysis and karyorrhexis), and cytoplasmic acidophilia. The pretreatment with 4 mg/kg (p.o.) of Ginkgo biloba extract (GbE), for 5 days, prevented most of the damage caused by CCl4: significantly decreased the serum activities of ALT and AST (54 and 65%, respectively), compared to CCl4-treated rats; GbE partially prevented the increase of liver MDA (55 +/- 14%) and the decrease of albumin concentration to 12 +/- 0.2%. This pretreatment prevented the down-regulation of TNF-alpha and up-regulated the interleukine 6 (IL-6) mRNA steady-state level. Moreover, the GbE reduced the amount of necrotic areas in the central lobe area, compared to CCl4-treated rats.
3: Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie, 2010 Jun 17, 273(1-3)
Hepatoprotective potential of aqueous extract of Butea monosperma against CCl(4) induced damage in rats.
[Abstract]Aqueous extract of flowers of Butea monosperma (Fabaceae) was evaluated at different dose levels (200, 400, 800mg/kg, p.o.) for its protective efficacy against CCl(4) (1.5ml/kg i.p.) induced acute liver injury to validate its use in traditional medicines. The CCl(4) administration altered various biochemical parameters, including serum transaminases, protein, albumin, hepatic lipid peroxidation, reduced glutathione and total protein levels, which were restored towards control by therapy of B. monosperma Adenosine triphosphatase and glucose-6-phosphatase activity in the liver were decreased significantly in CCl(4) treated animals. Therapy of B. monosperma showed its protective effect on biochemical and histopathological alterations at all the three doses in dose dependent manner. B. monosperma extract possess modulatory effect on drug metabolizing enzymes as it significantly decreased the hexobarbitone induced sleep time and increased excretory capacity of liver which was measured by BSP retention. Histological studies also supported the biochemical finding and maximum improvement in the histoarchitecture was seen at higher dose of BM extract.
4: World journal of gastroenterology : WJG, 2010 Jun 14, 16(22)
Protective effect of recombinant human IL-1Ra on CCl(4)-induced acute liver injury in mice.
[Abstract]AIM: To evaluate the effects of positive regulation of recombinant human interleukin 1 receptor antagonist (rhIL-1Ra) on hepatic tissue recovery in acute liver injury in mice induced by carbon tetrachloride (CCl(4)). METHODS: Acute liver damage was induced by injecting 8-wk-old mice with CCl(4) 1 mL/kg (1:3 dilution in corn oil) intraperitoneally (ip). Survival after liver failure was assessed by injecting 8-wk-old mice with a lethal dose of CCl(4) 2.6 mL/kg (1:1 dilution in corn oil) ip. Mice were subcutaneously injected with 1 mg/kg recombinant human IL-1Ra twice a day after CCl(4) treatment for 5 d. Serum alanine amino transferase (ALT) and aspartate aminotransferase (AST) levels were determined with a commercial assay kit. Serum IL-1beta, IL-1Ra levels were measured by enzyme-linked immunosorbent assay kit. Quantitative real-time polymerase chain reaction was used to determine liver IL-1beta, IL-1Ra and IL-6 expression during CCl(4)-induced acute liver injury. Liver sections were stained with hematoxylin-eosin. A histology-injury grading system was used to evaluate the degree of necrosis after acute liver injury. Proliferating cell nuclear antigen (PCNA) staining was used to evaluate the role of rhIL-1Ra in promoting hepatocyte proliferation. RESULTS: Quantitative analysis showed a higher level of IL-6 mRNA expression and reduced serum AST and ALT levels in the livers of the rhIL-1Ra-treated group at the early phase of CCl(4)-induced acute liver injury. Histological examination indicated a decrease in centrilobular necrotic areas in mice treated with rhIL-1Ra, and a novel role of rhIL-1Ra in promoting hepatocyte proliferation was also supported by an increase of PCNA staining. All these results, accompanied by a strong survival benefit in rhIL-1Ra-treated vs PBS-treated groups, demonstrated that rhIL-1Ra administration ameliorated the histological damage and accelerated the regeneration and recovery process of the liver. CONCLUSION: rhIL-1Ra could be further developed as a novel therapeutic agent for the treatment of acute liver injury because of its ability to reduce hepatocellular damage and facilitate liver regeneration.
5: Indian journal of biochemistry & biophysics, 2010 Apr, 47(2)
Hepatoprotective activity of leaves of Zanthoxylum armatum DC in CCl4 induced hepatotoxicity in rats.
[Abstract]Zanthoxylum armatum DC (Rutaceae) is extensively used in indigenous system of medicine as a tonic, carminative, stomachic and anthelmintic. In the present study, the hepatoprotective activity of the leaves ethanolic extract of Z. armatum (EEZA) was evaluated in CCl4-induced hepatotoxicity in rats. The extract at a dose of 500 mg/kg registered a significant decrease in the levels of serum glutamyl oxalacetic acid transaminase (SGOT), serum glutamyl pyruvate transaminase (SGPT), alkaline phosphatase (ALKP), and serum bilurubin (SBLN) and liver inflammation, which was supported by histopathological studies on liver, thus exhibited a significant hepatoprotective activity. The phytochemical screening of defatted ethanolic extract showed the presence of sterols, alkaloids, flavonoids, and reducing sugars.
6: Liver international : official journal of the International Association for the Study of the Liver, 2010 May 21, 58(10)
Rat CCl(4)-induced cirrhosis plus total portal vein ligation: a new model for the study of hyperammonaemia and brain oedema.
[Abstract]Abstract Introduction: Animal models used to study hyperammonaemic disorders related to chronic liver disease are unsatisfactory. These animals only develop hyperammonaemia and brain oedema when fed with diets supplemented with amonium acetate. Aim: To develop a novel experimental model of hyperammonaemia and brain oedema in CCl(4)-induced cirrhosis in rats. Methods: Four groups were studied: rats with sham intervention (S), rats with total portal vein ligation (TPVL), cirrhotic rats (LC), and cirrhotic rats with TPVL (LC+TPVL). When ascites was diagnosed, oral glutamine challenge (OGC) test was performed. Blood, liver, lungs and brain samples were collected to quantify liver function parameters, plasmatic and cerebral ammonia, endotoxaemia, liver and brain histology, brain oedema and portosystemic shunting degree. Results: LC+TPVL rats showed a significant increase in portosystemic shunting when compared with LC group and a significant derangement in liver function when compared with TPVL group. These alterations resulted in a significant increase in plasmatic and brain ammonia concentrations and a higher plasmatic endotoxaemia as compared with others. Similarly, the area under OGC curve was significantly increased in LC+TPVL group as compared with the others, and correlates with portal shunting. Low-grade brain oedema was only observed in LC+TPVL group. All cirrhotic groups showed liver regeneration nodules and type-II Alzheimer astrocytes Conclusion: LC+TPVL reproduce the main alterations - portosystemic shunting, plasmatic and cerebral hyperammonaemia and low-grade brain oedema - observed in cirrhotic patients with hepatic encephalopathy.
7: Zhonghua yi xue za zhi, 2010 Mar 30, 90(12)
[Observation on experimental liver fibrosis and hepatic carcinogenesis of HBV gene knock-in transgenic mice induced by CCl(4)/ethanol.]
[Abstract]OBJECTIVE: To study the effects of carbon tetrachloride (CCl(4))/ethanol induction upon experimental liver fibrosis and hepatic carcinogenesis of HBV transgenic mice. METHODS: The wild-type mice, p21-HBx transgenic mice with integration of p21 locus by HBx gene and p21-HBsAg transgenic mice with integration of p21 locus by HBsAg gene were induced separately by CCl(4)/ethanol twice weekly for 20 weeks. The investigators observed the development of liver fibrosis and hepatic carcinogenesis in three groups and detected the gene expressions of HBx and HBsAg by RT-PCR. RESULTS: The expression of HBx or HBsAg mRNA existed in both control and induced transgenic mice, but in none of wild-type mice. Comparing with wild-type mice, p21 genes was not expressed in livers of transgenic mice. After induction by CCl(4)/ethanol, the fibrotic degrees of liver were not significantly different among wild-type mice, p21-HBx transgenic mice and p21-HBsAg transgenic mice, as well as between male and female mice. Reversely, the incidence rates of hepatic carcinogenesis of two HBV gene knock-in transgenic mouse lines (p21-HBx & p21-HBsAg) were higher than that of wild-type mice. And the incidence rate of hepatic carcinogenesis in males was also markedly higher than that in females. Induction by CCl(4)/ethanol markedly promoted and accelerated hepatic carcinogenesis in transgenic mice. CONCLUSIONS: Integration of HBsAg and HBx genes into the murine p21 locus can significantly promote the progression of hepatic carcinogenesis, but failed to promote the progression of liver fibrosis. The male mouse is more likely to develop experimental hepatocellular carcinoma than the female mouse. Experimental hepatocellular carcinoma induced by CCl(4)/ethanol in p21-HBx and p21-HBsAg transgenic mice is a feasible animal model.
8: Journal of gastroenterology and hepatology, 2010 Mar, 25(3)
CCl4-induced hepatic injury in mice fed a Western diet is associated with blunted healing.
[Abstract]BACKGROUND AND AIMS: Feeding a Western diet (WD) enriched in saturated fat protects against chronic alcoholic hepatitis. However, saturated fat induces lipotoxicity in cultured hepatocytes. The purpose of the present study was to elucidate the influence of WD on acute hepatic injury and healing. METHODS: Male C57BL/6 mice were fed a purified control diet (CD) or WD enriched in palmitate and cholesterol. After 3 weeks, carbon tetrachloride (CCl(4)) was administered (0.1 microL/g, intraperitoneally). Hepatic inflammation and proliferation were assessed by immunostaining for neutrophils and intracellular adhesion molecule-1, and Ki67, respectively. Cytokine expression was analyzed by real-time polymerase chain reaction. Protein levels of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) were assessed by western blotting. RESULTS: Feeding a WD resulted in markedly greater histological evidence of necrosis and enhanced alanine aminotransferase activity (188 +/- 6.2 U/L) compared to CD-fed mice (99.1 +/- 6.3 U/L) by day 2 post-CCl(4). In contrast, WD blunted leukocyte accumulation in necrotic areas and the expression of cytokines (tumor necrosis factor-alpha and interleukin-6) involved in tissue regeneration. Diminished repair was further indexed by lower collagen-alphaI and Ki67 expression in the mice fed a WD. Finally, feeding a WD, as well as the treatment of cultured hepatocytes with palmitic acid, upregulated the expression of PPAR-gamma, which has been previously shown to prevent hepatic repair following CCl(4) exposure. CONCLUSIONS: These findings suggest that impaired healing in WD-fed mice blunted recovery from acute injury and underscored the complex relationship between diet and hepatic injury.
9: British journal of haematology, 2010 Mar 21, 114(12)
Monocytes/macrophages but not T lymphocytes are the major targets of the CCL3/CCL4 chemokines produced by CD38CD49d chronic lymphocytic leukaemia cells.
[Abstract]It is generally expected that ions in an aqueous ionic solution in contact with a hydrophobic phase enter the hydrophobic phase accompanied by a hydration shell. This expectation suggests that the ion mole fraction in the hydrophobic phase is less than, or at most, equal to that of water. Both gravimetric and spectroscopic evidence shows that for a model hydrophobic phase, carbon tetrachloride, this is not the case: In contact with a 1 M simple salt solution (sodium or potassium halide), the salt concentration in carbon tetrachloride ranges from 1.4 to nearly 3 times that of water. Infrared spectra of the OH stretch region support a model in which water associates with the cation, primarily as water monomers. Salts containing larger, more polarizable anions can form outer-sphere ion pairs that support water dimers, giving rise to a spectral signature at 3440 cm(-1). In CCl(4), the infrared spectral signature of the normally strongly ionized acid HCl clearly shows the presence of molecular HCl. Additionally, the presence of a Q branch for HCl indicates restricted rotational motion. The spectral and gravimetric data provide compelling evidence for ion clusters in the hydrophobic phase, which is a result that may have implications for hydrophobic matter in both biological and environmental systems.
10: Molecular endocrinology (Baltimore, Md.), 2010 Mar 8, 193(2)
FXR Regulates Liver Repair after CCl4-Induced Toxic Injury.
[Abstract]Liver repair is key to resuming homeostasis and preventing fibrogenesis as well as other liver diseases. Farnesoid X receptor (FXR, NR1H4) is an emerging liver metabolic regulator and cell protector. Here we show that FXR is essential to promote liver repair after carbon tetrachloride (CCl4)-induced injury. Expression of hepatic FXR in wild-type mice was strongly suppressed by CCl4 treatment, and bile acid homeostasis was disrupted. Liver injury was induced in both wild-type and FXR(-/-) mice by CCl4, but FXR(-/-) mice had more severe defects in liver repair than wild-type mice. FXR(-/-) livers had a decreased peak of regenerative DNA synthesis and reduced induction of genes involved in liver regeneration. Moreover, FXR(-/-) mice displayed increased mortality and enhanced hepatocyte deaths. During the early stages of liver repair after CCl4 treatment, we observed overproduction of TNFalpha and a strong decrease of phosphorylation and DNA-binding activity of signal transducer and activator of transcription 3 in livers from FXR(-/-) mice. Exogenous expression of a constitutively active signal transducer and activator of transcription 3 protein in FXR(-/-) liver effectively reduced hepatocyte death and liver injury after CCl4 treatment. These results suggest that FXR is required to regulate normal liver repair by promoting regeneration and preventing cell death.
11: The journal of physical chemistry. A, 2010 Mar 3, 12(5)
Ions and Hydrogen Bonding in a Hydrophobic Environment: CCl(4).
[Abstract]It is generally expected that ions in an aqueous ionic solution in contact with a hydrophobic phase enter the hydrophobic phase accompanied by a hydration shell. This expectation suggests that the ion mole fraction in the hydrophobic phase is less than, or at most, equal to that of water. Both gravimetric and spectroscopic evidence shows that for a model hydrophobic phase, carbon tetrachloride, this is not the case: In contact with a 1 M simple salt solution (sodium or potassium halide), the salt concentration in carbon tetrachloride ranges from 1.4 to nearly 3 times that of water. Infrared spectra of the OH stretch region support a model in which water associates with the cation, primarily as water monomers. Salts containing larger, more polarizable anions can form outer-sphere ion pairs that support water dimers, giving rise to a spectral signature at 3440 cm(-1). In CCl(4), the infrared spectral signature of the normally strongly ionized acid HCl clearly shows the presence of molecular HCl. Additionally, the presence of a Q branch for HCl indicates restricted rotational motion. The spectral and gravimetric data provide compelling evidence for ion clusters in the hydrophobic phase, which is a result that may have implications for hydrophobic matter in both biological and environmental systems.
12: Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology, 2010 Feb, 18(2)
[Effects of Smad4 on liver fibrosis and hepatocarcinogenesis in mice treated with CCl4/ethanol.]
[Abstract]To study the effects of Smad4 on liver fibrosis and hepatocarcinogenesis in mice treated with CCl4/ethanol. The wild-type mice (Smad4 +/+) and the Smad4 knockout mice (Smad4 +/-) were injected subcutaneously with carbon tetrachloride(CCl4)/ethanol twice a week for twenty weeks. The expression of Smad4, TGFbeta1, Smad2, Smad3, Smad6, TIMP1, MMP2 and MMP9 was detected by RT-PCR. In the cirrhotic liver, the expression of Smad4 mRNA was significantly higher than that in the normal liver. Comparing with wild-type mice (Smad4 +/+), the TGFbeta1-Smad4 signaling was markedly attenuated in the Smad4 knockout mice (Smad4 +/-). After induction by CCl4/ethanol, the hepatic fibrosis in the Smad4 knockout mice (Smad4 +/-) was obviously alleviated compared with the wild-type mice(Smad4 +/+), and the incidence rate of hepatocarcinogenesis of the former was also lower than that of the latter(32.0% vs 41.9%). These results indicate that knocking out Smad4 can delay the progression of liver fibrosis and liver cancer.
13: Phytotherapy research : PTR, 2009 Nov 19, 51(6)
Effects of Athamanta turbith fruit essential oils on CCl(4)-induced hepatic failure in mice and their antioxidant properties.
[Abstract]The effects of essential oils isolated from mature fruits of Athamanta turbith ssp. hungarica (Borb¨¢s) Tutin and A. turbith ssp. haynaldii (Borb¨¢s & Uechtr.) Tutin (Umbelliferae) on some liver biochemical parameters in mice intoxicated with carbon tetrachloride were investigated. Pretreatment with both essential oils extenuated the effects caused by carbon tetrachloride. In order to investigate in vitro antioxidant properties of the oils, three methods were applied: scavenging of both 2,2-diphenyl-1-picrylhydrazyl (DPPH) and OH radicals, as well as a test of inhibition of Fe(2+)/ascorbic-induced lipid peroxidation. Investigated essential oils exhibited modest antioxidant capacity. Therefore, their influence on biochemical parameters in intoxicated animals might be linked to the inhibition of enzymes (cytochrome P450 2E1) involved in metabolic activation of halomethanes. Copyright (c) 2009 John Wiley & Sons, Ltd.
14: Journal of hepatology, 2009 Oct 7, 15(38)
A novel model of CCl(4)-induced cirrhosis with ascites in the mouse.
[Abstract]BACKGROUND/AIMS: The current approaches to study the molecular mechanisms involved in the pathophysiology of liver diseases often rely on the use of transgenic mice. However, experimental models of decompensated cirrhosis have not been clearly established in mice. Thus, we aimed to set an efficient and well-tolerated protocol to induce cirrhosis in mice able to progress up to the ascitic stage. METHODS: C57BL/6N mice received CCl(4) subcutaneously, intraperitoneally or by inhalation. In the latter group, gaseous CCl(4) was administered according to three different schedules: increasing exposure times, twice weekly (traditional protocol; TP), short inhalation cycles, twice or three times weekly. RESULTS: Portal hypertension, sodium retention, and ascites developed in all groups between 11 and 15weeks. Mortality reached 70% in the TP group, but it was only 0-10% with all other protocols. All the inhalation groups had significantly more ascites at sacrifice than those receiving CCl(4) subcutaneously and intraperitoneally. Extensive abdominal adhesions and evidence of enhanced hepatic inflammation, as suggested by the increased gene expression of pro-inflammatory cytokines in liver tissue, were found in the intraperitoneal group, while large granulomas at the injection site and marked neutrophil infiltration of lungs developed in the subcutaneous group. No extra-hepatic damage could be detected in mice inhaling CCl(4). CONCLUSIONS: The use of short cycles of CCl(4) inhalation represents a novel, safe, and effective method to induce decompensated cirrhosis in mice. Intraperitoneal CCl(4) leads instead to abdominal adhesions precluding a correct evaluation of ascites, while subcutaneous CCl(4) causes an unwanted systemic inflammatory response.
15: Phytotherapy research : PTR, 2009 Oct 13, 15(38)
Oxidative stress modulation by Rosmarinus officinalis in CCl(4)-induced liver cirrhosis.
[Abstract]Rosmarinus officinalis (Lamiaceae) possesses antioxidant activity and hepatoprotective effects, and so may provide a possible therapeutic alternative for chronic liver disease. The effect produced by a methanolic extract of Rosmarinus officinalis on CCl(4)-induced liver cirrhosis in rats was investigated using both prevention and reversion models. Over the course of the development of cirrhosis, the increased enzymatic activities of gamma-glutamyl transpeptidase and alanine aminotransferase, and the rise in bilirubin levels caused by CCl(4) administration, were prevented by Rosmarinus officinalis co-administration. When the cirrhosis by oxidative stress was evaluated as an increase on liver lipoperoxidation, total lipid peroxides, nitric oxide in serum, and loss of erythrocyte plasma membrane stability, R. officinalis was shown to prevent such alterations. On cirrhotic animals treated with CCl(4), histological studies showed massive necrosis, periportal inflammation and fibrosis which were modified by R. officinalis. These benefits on experimental cirrhosis suggest a potential therapeutic use for R. officinalis as an alternative for liver cirrhosis. Copyright (c) 2009 John Wiley & Sons, Ltd.
16: World journal of gastroenterology : WJG, 2009 Oct 14, 15(38)
Emodin protects rat liver from CCl(4)-induced fibrogenesis via inhibition of hepatic stellate cells activation.
[Abstract]AIM: To investigate the role of emodin in protecting the liver against fibrogenesis caused by carbon tetrachloride (CCl(4)) in rats and to further explore the underlying mechanisms. METHODS: Rat models of experimental hepatic fibrosis were established by injection with CCl(4); the treated rats received emodin via oral administration at a dosage of 20 mg/kg twice a week at the same time. Rats injected with olive oil served as a normal group. Histopathological changes were observed by hematoxylin and eosin staining. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and hepatic hydroxyproline content were assayed by biochemical analyses. The mRNA and protein relevant to hepatic stellate cell (HSC) activation in the liver were assessed using real-time reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, western blotting and enzyme-linked immunosorbent assay. RESULTS: The degree of hepatic fibrosis increased markedly in the CCl(4) group compared to the normal group (P < 0.01), and decreased markedly in the emodin group compared to the CCl(4) group according to METAVIR scale (P < 0.01) compared with those in the normal control group (51.02 +/- 10.64 IU/L and 132.28 +/- 18.14 IU/L). The activities of serum ALT and AST were significantly higher in rats injected with CCl(4) (289.25 +/- 68.84 IU/L and 423.89 +/- 35.67 IU/L, both P < 0.05). The activities of serum ALT and AST were significantly reduced by administration of emodin (176.34 +/- 47.29 IU/L and 226.1 +/- 44.52 IU/L, both P < 0.05). Compared with the normal controls (54.53 +/- 13.46 mg/g), hepatic hydroxyproline content was significantly higher in rats injected with CCl(4) (120.27 +/- 28.47 mg/g, P < 0.05). Hepatic hydroxyproline content was significantly reduced in the rats treated with emodin at 20 mg/kg (71.25 +/- 17.02 mg/g, P < 0.05). Emodin significantly protected the liver from injury by reducing serum AST and ALT activities and reducing hepatic hydroxyproline content. The mRNA levels of transforming growth factor-beta1 (TGF-beta1), Smad4 and alpha-SMA in liver tissues were significantly down-regulated in SD rats that received emodin treatment. Furthermore, significant down-regulation of serum TGF-beta1 protein levels and protein expression of Smad4 and alpha-SMA in liver tissues was also observed in the rats. Emodin inhibited HSC activation by reducing the abundance of TGF-beta1 and Smad4. CONCLUSION: Emodin protects the rat liver from CCl(4)-induced fibrogenesis by inhibiting HSC activation. Emodin might be a therapeutic antifibrotic agent for the treatment of hepatic fibrosis.
17: Pakistan journal of pharmaceutical sciences, 2009 Oct, 22(4)
Effect of ethanol extract of flowers of vitex trifolia linn. on CCL(4) induced hepatic injury in rats.
[Abstract]Hepatoprotective activity of ethanolic extract of flowers of Vitex trifolia (Verbenaceae) was studied against CCl(4) induced hepatic injury in albino rats. The plant extract (EVT) at the dose of 200 mg/kg, p.o. showed a remarkable hepatoprotective activity. CCl(4) induced a significant rise in serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin and gamma glutamate transpeptidase (GGTP). Treatment of rats with EVT significantly (P<0.001) altered serum biomarker enzyme levels to near normal against CCl(4) treated rats. The activity of the extract was comparable to the standard drug, silymarin (100 mg/kg, p.o.). Histopathological observations also revealed that treatment with EVT protected the animals from CCl(4) induced liver damage. The results indicate that the flowers of V. trifolia possess hepatoprotective activity on CCl(4) induced hepatic injury in rats.
18: Indian journal of experimental biology, 2009 Aug, 47(8)
Hepatoprotective effect of Carissa carandas Linn root extract against CCl4 and paracetamol induced hepatic oxidative stress.
[Abstract]Oral pre-treatment with ethanolic extract of the roots of C. carandas (ERCC; 100, 200 and 400 mg/kg, po) showed significant hepatoprotective activity against CCl4 and paracetamol induced hepatotoxicity by decreasing the activities of serum marker enzymes, bilirubin and lipid peroxidation, and significant increase in the levels of uric acid, glutathione, super oxide dismutase, catalase and protein in a dose dependent manner, which was confirmed by the decrease in the total weight of the liver and histopathological examination. Data also showed that ERCC possessed strong antioxidant activity, which may probably lead to the promising hepatoprotective activities of C. carandas root extract. These findings therefore supported the traditional belief on hepatoprotective effect of the roots of C. carandas.
19: Indian journal of experimental biology, 2009 Jul, 47(7)
Antioxidant and hepatoprotective activities of Ocimum basilicum Linn. and Trigonella foenum-graecum Linn. against H2O2 and CCL4 induced hepatotoxicity in goat liver.
[Abstract]Significant hepatoprotective effects were obtained by ethanolic extract of leaves of O. basilicum and T. foenum-graecum against liver damage induced by H2O2 and CCl4 as evidenced by decreased levels of antioxidant enzymes (enzymatic and non enzymatic). The extract also showed significant anti lipid peroxidation effects in vitro, besides exhibiting significant activity in superoxide radical and nitric oxide radical scavenging, indicating their potent antioxidant effects.
20: Histochemistry and cell biology, 2009 Sep 16, 113(38)
Global gene expression profiling reveals a key role of CD44 in hepatic oval-cell reaction after 2-AAF/CCl(4) injury in rodents.
[Abstract]Liver progenitors, so-called oval cells, proliferate remarkably from periportal areas after severe liver injury when hepatocyte regeneration is compromised. These cells invade far into the liver parenchyma. Molecular mechanisms underlying these behaviors of oval cells remain poorly understood. In this study, we treated rats with 2-acetylaminofluorene/carbon tetrachloride to induce hepatic oval cells. By expression microarray analysis, we investigated global gene expression profiles in liver tissue, with an emphasis on adhesion molecules, extracellular matrix proteins, matrix metalloproteinases (MMPs), growth factors/cytokines, and receptors that might contribute to the distinct behaviors of oval cells. Genes upregulated at least twofold were selected. We then performed immunostaining to verify the microarray results and identified expression of MMP-7 and CD44 in oval cells. Staining of cytokeratin (CK)-19, an oval-cell marker, was similar between oval cells located next to periportal areas and those located far within the parenchyma. In contrast, CD44 staining was more intense in the parenchyma than in periportal areas, suggesting a role of CD44 in oval-cell invasion. Moreover, newly differentiated CK-19(+) hepatocytes within foci did not show CD44 staining, suggesting that CD44 is related to the undifferentiated oval-cell phenotype. We then investigated oval-cell reactivity in CD44-deficient mice fed an oval cell-inducing diet of 3,5-diethoxycarbonyl-1,4-dihydrocollidine. Results showed significantly reduced oval-cell reactivity in CD44-deficient mice. Thus, oval cells express MMP-7 and CD44, and CD44 appears to play critical roles in the proliferation, invasion, and differentiation of hepatic oval cells in rodents.
21: Journal of medicinal food, 2009 Aug, 12(4)
Protective effect of Millettia reticulata Benth against CCl(4)-induced hepatic damage and inflammatory action in rats.
[Abstract]The effects of the water extracts of Millettia reticulata Benth (WEMRB) and its active compound (protocatechuic acid [PCA]) on acute hepatic injury and inflammation in CCl(4)-induced Sprague-Dawley rats were investigated. Sprague-Dawley rats were orally treated with WEMRB or PCA for 28 consecutive days, and then the rats were given an intraperitoneal injection with CCl(4). Pretreatment with WEMRB or PCA significantly lowered the CCl(4)-induced serum levels of hepatic enzyme markers (aspartate and alanine aminotransferases). Liver histopathology showed that WEMRB reduced the incidence of cytoplasmic vacuolization and necrosis induced by CCl(4) in rats. Pretreatment with WEMRB also showed anti-inflammation on the expression of cyclooxygenase-2, inducible nitric oxide synthase, and myeloperoxidase, as well as nitrite and nitrate levels in the CCl(4)-induced Sprague-Dawley rats. The results suggest that oral administration of WEMRB decreases the hepatotoxic effects by increasing glutathione-dependent antioxidant enzyme activity, thereby reducing oxidative stress and inflammation in CCl(4)-induced Sprague-Dawley rats.
22: The journal of physical chemistry. A, 2009 Sep 24, 113(38)
Formation of active catalysts in the system: chlorocuprates-CCl4-n-C10H22.
[Abstract]Transformations of anionic Cu(II) chlorocomplexes have been studied under conditions of catalytic exchange reactions between carbon tetrachloride and n-alkanes. It was shown that chlorocuprates are just precursors and are easily reduced to the genuine catalysts, that is, to the respective Cu(I) complexes. Both the composition and the geometric structure of the precursor (CuCl(4)(2-)) and, probably, the active site (CuCl(3)(2-)) have been investigated by several techniques (UV-vis spectroscopy, electron spin resonance (ESR), extended X-ray absorption fine structure (EXAFS), X-ray absorption near-edge structure (XANES), and static magnetic measurements). The dependence of the metathesis velocity on the [Cl-]/[Cu] ratio was found to exhibit a maximum most likely corresponding to the highest content of trichlorocuprite CuCl(3)(2-).
23: Journal of leukocyte biology, 2009 Oct, 86(4)
An arrestin-dependent multi-kinase signaling complex mediates MIP-1beta/CCL4 signaling and chemotaxis of primary human macrophages.
[Abstract]MIP-1beta/CCL4 is a principal regulator of macrophage migration and signals through CCR5. Several protein kinases are linked to CCR5 in macrophages including the src kinase Lyn, PI3K, focal adhesion related kinase Pyk2, and members of the MAPK family, but whether and how these kinases regulate macrophage chemotaxis are not known. To define the role of these signaling molecules, we examined the functions and interactions of endogenous proteins in primary human macrophages. Using siRNA gene silencing and pharmacologic inhibition, we show that chemotaxis in response to CCR5 stimulation by MIP-1beta requires activation of Pyk2, PI3K p85, and Lyn, as well as MAPK ERK. MIP-1beta activation of CCR5 triggered translocation of Pyk2 and PI3K p85 from the cytoplasm to colocalize with Lyn at the plasma membrane with formation of a multimolecular complex. We show further that arrestins were recruited into the complex, and arrestin down-regulation impaired complex formation and macrophage chemotaxis toward MIP-1beta. Together, these results identify a novel mechanism of chemokine receptor regulation of chemotaxis and suggest that arrestins may serve as scaffolding proteins linking CCR5 to multiple downstream signaling molecules in a biologically important primary human cell type.
24: Chemico-biological interactions, 2009 Oct 30, 181(3)
Isolation, characterization and antioxidative effect of phyllanthin against CCl4-induced toxicity in HepG2 cell line.
[Abstract]The present study was an attempt to investigate the hepatoprotective and antioxidative property of Phyllanthus amarus (P. amarus) extract and phyllanthin. Phyllanthin, one of the active lignin present in this plant species was isolated from the aerial parts, by silica gel column chromatography employing gradient elution with hexane-ethyl acetate solvent mixture. It was obtained in high yields (1.23%), compared to reported procedures and the purity was ascertained by HPTLC and reversed-phase HPLC analysis. Characterization of phyllanthin was done by mp, UV-Visible spectrophotometry, elemental analysis, FT-IR, 1H NMR, 13C NMR and mass spectral analysis. Free radical scavenging activity of P. amarus extract and phyllanthin was also examined using DPPH assay. The protective effect of P. amarus extract and phyllanthin was studied on CCl4-induced toxicity in human hepatoma HepG2 cell line. The results indicated that CCl4 treatment caused a significant decrease in cell viability. In addition, the toxin treatment initiated lipid peroxidation (LPO), caused leakage of enzymes like alanine transaminase (ALT) and lactate dehydrogenase (LDH) with a significant decrease in glutathione (GSH) levels. It was observed that phyllanthin effectively alleviated the changes induced by CCl4 in a concentration-dependent manner, with much smaller strengths as compared to P. amarus extract.
25: Physical chemistry chemical physics : PCCP, 2009 Jul 7, 11(25)
Ar, CCl(4) and C(6)H(6) adsorption outside and inside of the bundles of multi-walled carbon nanotubes-simulation study.
[Abstract]This is the first paper reporting the results of systematic study of the adsorption of Ar, C(6)H(6) and CCl(4) on the bundles of closed and opened multi-walled carbon nanotubes. Using grand canonical Monte Carlo (GCMC) and molecular dynamics (MD) simulations, we also study the effect of the introducing defects in the external and internal walls of osculating and separated nanotubes on Ar diffusion and on adsorption of all three adsorbates. The Ar diffusion coefficients obtained are very sensitive to the presence of defects. Simulated isotherms are discussed to show the relation between the shapes of the high resolution alpha(s)-plots and the mechanisms of adsorption. From obtained data, as well as from geometric considerations, from the VEGA ZZ package, and from simulations (ASA), the values of surface areas of all nanotubes are calculated and compared with those obtained using the most popular adsorption methods (BET, alpha(s) and the A,B,C-points). We show that the adsorption value for the C-point of the isotherm should be taken for the calculation of the specific surface area of carbon nanotubes to obtain a value which approaches the absolute geometric surface area. A fully packed monolayer is not created at the A-, B- or C-points of the isotherm; however, the number of molecules adsorbed at the latter point is closest to the number of molecules in the monolayer as calculated via the ASA method, the VEGA ZZ package or from geometric considerations.
26: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2009 Sep, 47(9)
Absorption of andrographolides from Andrographis paniculata and its effect on CCl(4)-induced oxidative stress in rats.
[Abstract]A simple and validated high-performance liquid chromatography (HPLC) method with UV detection has been used to determine the content of andrographolide (AP) and 14-deoxy-11,12-didehydroandrographolide (DIAP) in rat plasma after oral dose of methanol extract (1 g/kg body weight) of Andrographis paniculata leaf. An increase in plasma concentration of AP and DIAP was observed from 30 min to 3 h after oral administration of the extract. The maximum plasma concentrations of AP and DIAP were 1.42+/-0.09 microg/ml and 1.31+/-0.04 microg/ml, respectively. Fourteen days oral treatment of rats with the methanol extract (1 g/kg body weight) followed by CCl(4) administration preserved catalase (CAT), and superoxide dismutase (SOD) activities in erythrocytes, whereas plasma lipid peroxidation, alanine transaminase (ALT) and aspartate transaminase (AST) activities were restored to values comparable with control values. Treatment of rats with CCl(4) did not showed significant alteration (p>0.05) in plasma total antioxidant status (TAS) as compare to values of control group.
27: European journal of clinical investigation, 2009 Oct, 39(10)
Vascular hyporesponsiveness to angiotensin II in rats with CCl(4)-induced liver cirrhosis.
[Abstract]BACKGROUND: Portal hypertension is triggered by vasodilation due to impaired contraction of extrahepatic vessels. Angiotensin II type 1 (AT(1)) receptor-induced vasocontraction is mediated by G proteins and may be desensitized by recruitment of beta-arrestin-2 to the receptor. In this study, we analysed the interaction of AT(1) receptors with beta-arrestin-2 in the context of vascular hypocontractility in rats with CCl(4)-induced cirrhosis. METHODS: Micronodular liver cirrhosis in rats (n = 15) was induced by regular CCl(4) exposure. Age-matched rats (n = 15) served as controls. Contractility of aortic rings was measured by myography. Protein expressions and phosphorylations were assessed by Western blot analysis, and AT(1) receptor interaction with beta-arrestin-2 by co-immunoprecipitation. RESULTS: Aortic rings from CCl(4) rats were hypocontractile to angiotensin II independent of nitric oxide synthases (Nomega-nitro-l-arginine methyl ester 200 microM). Expression of the AT(1) receptor, Galpha(q/11) and the contraction-mediating effector Rho kinase was similar in aortas from both groups. Expression and AT(1) receptor binding of beta-arrestin-2 were up-regulated in aortas from CCl(4) rats. Stimulation of isolated aortas with exogenous angiotensin II caused recruitment of beta-arrestin-2 in aortas from noncirrhotic rats, but no further interaction of AT(1) receptors with beta-arrestin-2 was found in aortas from CCl(4) rats. While angiotensin II stimulation resulted in Rho kinase activation in aortas from noncirrhotic rats but not in aortas from CCl(4) rats, extracellular signal-regulated kinase activation in response to angiotensin II was observed in aortas from both groups. CONCLUSIONS: Vascular hyporesponsiveness to angiotensin II in CCl(4) rats is due to enhanced interaction of the AT(1) receptor with beta-arrestin-2 and consecutively changed receptor function.
28: Journal of colloid and interface science, 2009 Sep 1, 337(1)
Complex permittivity of FeCl3/AOT/CCl4 microemulsions probed by AC impedance spectroscopy.
[Abstract]The complex permittivity of FeCl(3)/AOT/CCl(4) microemulsions in the 1-10(5) Hz frequency range has been measured by the conventional AC complex impedance technique. Measurements as a function of the volume fraction of the dispersed phase (FeCl(3)+AOT) and temperature at fixed salt-to-AOT molar ratio (R, R = 0.5) show that the entrapment of FeCl(3) clusters significantly enhances the local permittivity of the AOT reverse micelles and the number density of charge carriers resulting from the peculiar state of the confined inorganic salt. An estimate of the apparent static permittivity of the FeCl(3) ionic clusters entrapped in the core of AOT reverse micelles gives the very high and quite surprisingly value of about 237. Moreover, a thorough analysis of conductivity data and of their temperature dependence strongly supports the hypothesis that the charge transport in these systems is mainly sustained by a mechanism of hopping consisting in the continuous jumping of charged species within supra-micellar aggregates of AOT reverse micelles whose aggregation is driven by fluctuating opposite charges on contacting micelles.
29: Journal of ethnopharmacology, 2009 Sep 7, 125(2)
Hepatoprotective and antioxidant activity of Amaranthus spinosus against CCl4 induced toxicity.
[Abstract]AIM: 50% ethanolic extract (ASE) of Amaranthus spinosus (whole plant) was evaluated for in vitro antioxidant and hepatoprotective activity. METHODS: The total phenolics and reducing capacity of ASE was determined using standard curve of gallic acid (0-1.0mg/ml) and butylated hydroxy anisole. In vitro antioxidant activity was determined by DPPH, superoxide, hydroxyl radicals, hydrogen peroxide and nitric oxide scavenging methods. The hepatoprotective activity of ASE was evaluated at 6, 7, 8, 9 and 10 microg/ml concentration against CCl(4) (1%) induced toxicity in freshly isolated rat hepatocytes and HepG2 cells. RESULTS: ASE was found to contain 336+/-14.3mg/g total polyphenolics expressed as gallic acid equivalent while the reducing capacity was 2.26 times of BHA. ASE showed significant antioxidant activity in DPPH assay (IC(50) 29 microg/ml), scavenges superoxide (IC(50) approximately 66-70 microg/ml), hydrogen peroxide (IC(50) approximately 120-125 microg/ml), hydroxyl radicals (IC(50) approximately 140-145 microg/ml) and nitric oxide (IC(50) approximately 135-140 microg/ml). ASE (6, 7, 8, 9 and 10 microg/ml) was able to normalise the levels of biochemical parameters in isolated rat hepatocytes intoxicated with CCl(4). A dose dependent increase in percentage viability was observed in CCl(4) intoxicated HepG2 cells. CONCLUSIONS: ASE possesses significant hepatoprotective activity which might be due to antioxidant defence factors and phenolics might be the main constituents responsible for activity.
30: International journal of molecular medicine, 2009 Jun, 23(6)
Expression of angiotensin-converting enzyme 2 in CCL4-induced rat liver fibrosis.
[Abstract]The renin angiotensin system (RAS) plays a major role in liver fibrosis. A novel homologue of angiotensin converting enzyme, ACE2, was identified as a negative regulator of RAS as it degrades Ang II to Ang1-7. We investigated in vivo the expression of ACE2 in liver fibrosis. We evaluated the relationship between biochemical variables and liver tissue expression of ACE2, the correlation between a histological assessment of liver fibrosis and liver tissue expression of ACE2. Male SD rats were randomly divided into a CCL4 group which received injections of CCL4 and the control group which received injections of olive oil. Liver pathology was examined by H&E and Sirius red staining, and real-time PCR was performed to determine the gene expression levels of ACE2 and ACE. Real-time PCR analysis revealed that ACE2 mRNA was higher at the two-, four-, and six-week time points, respectively (p<0.01). Similarly, hepatic ACE mRNA was significantly increased after CCL4 injection. There was a significant correlation between ACE and ACE2 gene expression (r=0.750, P<0.001). ACE2 gene expression strongly correlated with ALT (r=0.669, P<0.0001) and AST levels (r=0.815, P<0.0001). There was a significant correlation between circulating ACE2 and histological scores of liver fibrosis. ACE2 and ACE gene expression correlated with the ISHAK score (r=0.850, P<0.001; r=0.806, P<0.001). There was a significant relationship between ACE2 gene expression and the degree of liver fibrosis. ACE2 plays a crucial role in liver fibrogenesis.
31: European journal of pharmacology, 2009 Jun 24, 613(1-3)
Combined use of propranolol and nifedipine offers better effects on portal vein nonuniform remodeling in carbon tetrachloride (CCl(4))-induced portal hypertensive rats.
[Abstract]Portal hypertension is a hemodynamic syndrome due to pathological increase in portal flow and portal pressure. These pathological changes in external flow loads will inevitably cause vascular remodeling in the portal vein, which is usually measured by an opening angle. The present study showed that carbon tetrachloride (CCl(4))-induced portal hypertension fully developed at 8 weeks and the opening angle of portal vein increased progressively in the pathogenesis of intrahepatic portal hypertension which was significantly augmented at 10 weeks. Although portal pressure and portal flow were reduced, treatment with either propranolol or nifedipine alone for 3 weeks did not decrease the augmented opening angle of the portal vein, while combined treatment with propranolol and nifedipine markedly reduced the increased opening angle of the portal vein and endothelial nitric oxide synthase (eNOS) mRNA expression but not inducible nitric oxide synthase (iNOS) mRNA expression. The decreasing effect of propranolol plus nifedipine on the elevated opening angle was significantly weakened by L-arginine and markedly reinforced by N-nitro-l-arginine-mythel-ester (L-NAME). These results indicate that combined use of propranolol and nifedipine ameliorates portal vein remodeling in portal hypertension at least by the nitric oxide-dependent way.
32: Biomedicine & pharmacotherapy = Biom¨¦decine & pharmacoth¨¦rapie, 2009 Sep, 63(8)
Protective effects of transgene expressed human PON3 against CCl4-induced subacute liver injury in mice.
[Abstract]Oxidative stress plays a crucial role in both initiation and progression of liver injury in almost all experimental and clinical liver diseases. Antioxidative therapy is therefore an effective means of preventing and attenuating oxidative stress related liver diseases. Human paraoxonase 3 (hPON3) is a lipid-associated enzyme with antioxidant activity. In the present study, hPON3 cDNA gene was cloned into pcDNA3.1 plasmid and electro-transferred into mouse skeletal muscle to maintain a higher serum PON3 activity. After gene delivery, serum PON3 activity was about 1.4 times higher than those of control and PON3 mRNA expression was also detected in mouse skeletal muscle. To investigate the role of hPON3 in protecting mice against liver injury, subacute liver injury model was induced by repeated CCl(4) administration and hPON3 gene was delivered into mouse skeletal muscle before progression or recovery phase, respectively, of liver injury. Afterwards, the mice were euthanized to evaluate liver marker enzymes, degrees of oxidative stress and liver histological architecture in order to reveal the effects of PON3 on subacute liver injury. In both damage phases, delivery of hPON3 gene significantly reduced serum aminotransferase level and improved liver histological architecture. Moreover, transgene expression of hPON3 attenuated oxidative stress by increasing hepatic glutathione content, superoxide dismutase (SOD) activity, total antioxidant capability (T-AOC), and reducing malondialdehyde (MDA) level.
33: The Journal of chemical physics, 2009 Feb 14, 130(6)
Nanometer range correlations between molecular orientations in liquids of molecules with perfect tetrahedral shape: CCl(4), SiCl(4), GeCl(4), and SnCl(4).
[Abstract]Neutron and x-ray weighted total scattering structure factors of liquid carbon, silicon, germanium, and tin tetrachlorides, CCl(4), SiCl(4), GeCl(4), and SnCl(4), have been interpreted by means of reverse Monte Carlo modeling. For each material the two sets of diffraction data were modeled simultaneously, thus providing sets of particle coordinates that were consistent with two experimental structure factors within errors. From these particle configurations, partial radial distribution functions, as well as correlation functions characterizing mutual orientations of molecules as a function of distance between molecular centers were calculated. Via comparison with reference systems, obtained by hard sphere Monte Carlo simulations, we demonstrate that orientational correlations characterizing these liquids are much longer ranged than expected, particularly in carbon tetrachloride.
34: The journal of physical chemistry. B, 2009 Feb 6, 130(6)
Outer Sphere Electroreduction of CCl(4) in 1-Butyl-3-methylimmidazolium Tetrafluoroborate: An Example of Solvent Specific Effect of Ionic Liquid.
[Abstract]Neutron and x-ray weighted total scattering structure factors of liquid carbon, silicon, germanium, and tin tetrachlorides, CCl(4), SiCl(4), GeCl(4), and SnCl(4), have been interpreted by means of reverse Monte Carlo modeling. For each material the two sets of diffraction data were modeled simultaneously, thus providing sets of particle coordinates that were consistent with two experimental structure factors within errors. From these particle configurations, partial radial distribution functions, as well as correlation functions characterizing mutual orientations of molecules as a function of distance between molecular centers were calculated. Via comparison with reference systems, obtained by hard sphere Monte Carlo simulations, we demonstrate that orientational correlations characterizing these liquids are much longer ranged than expected, particularly in carbon tetrachloride.
35: Ultrasonics sonochemistry, 2008 Dec 27, 130(6)
Sonochemical decay of C.I. Acid Orange 8: Effects of CCl(4) and t-butyl alcohol.
[Abstract]Sonochemical degradation of aryl-azo-naphthol dyes represented by C.I. Acid Orange 8 was investigated at 300kHz to assess the operational parameters and the impacts of rate enhancers (CCl(4)) and rate inhibitors (t-butyl alcohol). It was found that the degradation of the dye was accelerated with increased concentrations of CCl(4) via the accumulation of reactive chlorine species and the hindrance of OH radical combination reactions with atomic hydrogen. The addition of t-butyl alcohol at all test concentrations inhibited the degradation of the dye regardless of the quantity of OH radicals (or H(2)O(2)) in solution. The inhibition was explained by the competition of the dye and t-butyl alcohol at the gas-liquid interface. Finally, the rate of dye degradation in the presence of both reagents at their effective concentrations was found to be considerably slower than that with CCl(4), showing that the formation of reactive chlorine species was remarkably suppressed by the rapid reaction of t-butyl alcohol at the gas-liquid interface.
36: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2008 Dec 29, 130(6)
Methoxy VO-salen complex: In vitro antioxidant activity, cytotoxicity evaluation and protective effect on CCl(4)-induced oxidative stress in rats.
[Abstract]Reactive oxygen species (ROS) play crucial roles in normal physiological processes. However, the overproduction of ROS is involved in the onset of many degenerative diseases. Regarding this fact, discovery of new antioxidants is interesting for many research groups. In this study, we evaluated the antioxidant properties of a methoxy VO-salen (MetVO-salen) complex employing various in vitro systems. In addition, the cytotoxic effect of MetVO-salen was assessed based on MTT in treated K562 cells. In an in vivo approach, the protective effect of MetVO-salen against CCl(4)-induced oxidative stress in rats was also investigated in terms of superoxide dismutase (SOD) and catalase (CAT) activities, as well as in terms of the levels of malondialdehyde (MDA) and glutathione (GSH). Our results indicated that MetVO-salen has an effective capability in scavenging superoxide (O(2)(-)) and hydrogen peroxide (H(2)O(2)) radicals in a dose-dependent manner. In vivo results also showed that the administration of MetVO-salen to the CCl(4)-treated rats caused a significant (222%) increase in SOD activity, a 59% enhancement in GSH content and a 31% decrease in the level of MDA compared to the CCl(4)-treated control rats. Overall, MetVO-salen appears to be an effective antioxidant and is quite suitable for further biological evaluation.
37: International journal of experimental pathology, 2008 Dec, 89(6)
Embryonic stem cells reduce liver fibrosis in CCl4-treated mice.
[Abstract]We transplanted undifferentiated embryonic stem (ES) cells into the spleens of carbon tetrachloride (CCl(4))-treated mice to determine their effects on liver fibrosis. Carbon tetrachloride at 0.5 ml/kg of body weight was injected intraperitoneally into C57BL/6 mice twice weekly for up to 20 weeks. Four weeks after the first injection, the mice were divided into two groups and those in group 1 received 1 x 10(5) ES cells genetically labelled with enhanced green fluorescent protein (GFP) in the spleens, while group 2 mice received 0.1 ml of phosphate-buffered saline. In group 1, GFP-immunopositive cells were retained and found in areas of fibrosis in the liver, and reduced liver fibrosis was observed as compared with group 2. Secondary transplantation of ES cells at 12 weeks after the initial transplantation enhanced the reduction in liver fibrosis. No teratoma formation or uncontrolled growth of ES cells in organs, including the liver and spleen, was observed in any of the mice. In the livers of group 1 mice, metalloproteinase 9-immunopositive cells derived from ES cells as well as those from the recipient were observed. These cells were also found to be immunopositive for the hepatoblast marker Delta-like (DlK-1), a member of the DlK-1 family of transmembrane proteins. These results suggest that ES-based cell therapy is potentially useful for liver fibrosis treatment and that reduction in CCl(4)-induced liver fibrosis by transplantation of ES cells may be related closely to the emergence of metalloproteinase-producing hepatoblast-like cells.
38: Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials, 2008 Aug, 31(8)
[Research on active part of Sambucus chinensis against hepatitis mice induced by CCl4]
[Abstract]OBJECTIVE: To investigate the best extraction process of Sambucus chinensis against hepatitis and research on its active part. METHODS: We studied the protective effects of different extracts of Sambucus chinensis distilled by different extraction process on mice acute hepatic injury induced by CCl4, and searched for the active part of Sambucus chinensis against hepatitis from the best extract by extraction with different solvent and purification with macroporous adsorption resin, then studied their protective effects on mice acute hepatic injury induced by CCl4. RESULTS: The extraction of Sambucus chinensis by 75% alcohol showed very significantly protective effects on mice acute hepatic injury induced by CCl4 and the effects were better than that of other extraction process. The extraction eluted by 30% alcohol after purification with macroporous adsorption resin and extracted by EtOAc in the extraction of Sambucus chinensis by 75% alcohol all showed significantly protective effects on mice acute hepatic injury induced by CCl4, and the effects of the extraction eluted by 30% alcohol after purification with macroporous adsoption resin were better than extraction with EtOAc. CONCLUSIONS: The best extraction solvent is 75% alcohol. The active part of Sambucus chinensis against hepatitis is the extraction eluted by 30% alcohol after purification with macroporous adsorption resin and extraction with EtOAc.