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CCl4 Treatment (ccl4 + treatment)
Selected AbstractsCX3CL1-CX3CR1 interaction prevents carbon tetrachloride-induced liver inflammation and fibrosis in mice,HEPATOLOGY, Issue 4 2010Tomonori Aoyama Chronic liver disease is associated with hepatocyte injury, inflammation, and fibrosis. Chemokines and chemokine receptors are key factors for the migration of inflammatory cells such as macrophages and noninflammatory cells such as hepatic stellate cells (HSCs). The expression of CX3CR1 and its ligand, CX3CL1, is up-regulated in chronic liver diseases such as chronic hepatitis C. However, the precise role of CX3CR1 in the liver is still unclear. Here we investigated the role of the CX3CL1-CX3CR1 interaction in a carbon tetrachloride (CCl4),induced liver inflammation and fibrosis model. CX3CR1 was dominantly expressed in Kupffer cells in the liver. In contrast, the main source of CX3CL1 was HSCs. Mice deficient in CX3CR1 showed significant increases in inflammatory cell recruitment and cytokine production [including tumor necrosis factor , (TNF-,); monocyte chemoattractant protein 1; macrophage inflammatory protein 1,; and regulated upon activation, normal T cell expressed, and secreted (RANTES)] after CCl4 treatment versus wild-type (WT) mice. This suggested that CX3CR1 signaling prevented liver inflammation. Kupffer cells in CX3CR1-deficient mice after CCl4 treatment showed increased expression of TNF-, and transforming growth factor , and reduced expression of the anti-inflammatory markers interleukin-10 (IL-10) and arginase-1. Coculture experiments showed that HSCs experienced significantly greater activation by Kupffer cells from CCl4 -treated CX3CR1-deficient mice versus WT mice. Indeed, augmented fibrosis was observed in CX3CR1-deficient mice versus WT mice after CCl4 treatment. Finally, CX3CL1 treatment induced the expression of IL-10 and arginase-1 in WT cultured Kupffer cells through CX3CR1, which in turn suppressed HSC activation. Conclusion: The CX3CL1-CX3CR1 interaction inhibits inflammatory properties in Kupffer cells/macrophages and results in decreased liver inflammation and fibrosis. (Hepatology 2010) [source] Rating of CCl4 -induced rat liver fibrosis by blood serum glycomicsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2007Liesbeth Desmyter Abstract Background:, Non-invasive staging of human liver fibrosis is a desirable objective that remains under extensive evaluation. Animal model systems are often used for studying human liver disease and screening antifibrotic compounds. The aim of the present study was to investigate the potential use of serum N-glycan profiles to evaluate liver fibrosis in a rat model. Methods:, Liver fibrosis and cirrhosis were induced in rats by oral administration of CCl4. Liver injury was assessed biochemically (alanine aminotransferase [ALT] activity, aspartate aminotransferase [AST] activity and total bilirubin) and histologically. The N-glycan profile (GlycoTest) was performed using DNA sequencer-assisted,fluorophore-assisted carbohydrate electrophoresis technology. In parallel, the effect of cotreatment with antifibrotic interferon-, (IFN-,) was studied. Results:, The biopsy scoring system showed that CCl4 induced early fibrosis (F < 1,2) in rats after 3 weeks of treatment, and cirrhosis (F4) after 12 weeks. Significant increases in ALT activity, AST activity and total bilirubin levels were detected only after 12 weeks of CCl4 treatment. GlycoTest showed three glycans were significantly altered in the CCl4 -goup. Peak 3 started at week 6, at an early stage in fibrosis development (F < 1,2), whereas peaks 4 and 5 occurred at week 9, at which time mild liver fibrosis (F = 1,2) had developed. The changes in the CCl4 -IFN-, group were intermediate between the CCl4 - and the control groups. Conclusion:, The GlycoTest is much more sensitive than biochemical tests for evaluating liver fibrosis/cirrhosis in the rat model. The test can also be used as a non-invasive marker for screening and monitoring the antifibrotic activity of potential therapeutic compounds. [source] Subcellular redistribution of protein kinase C isozymes is associated with rat liver cirrhotic changes induced by carbon tetrachloride or thioacetamideJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 1 2001Da-Hee Jeong Abstract Background and Aims: Protein kinase C (PKC) plays a key role in the alteration of signal transduction in the liver, which may contribute to the development of liver cirrhosis. The aim of the present study was to examine the subcellular redistribution of PKC isozymes in rat liver cirrhosis, which is induced by two different cirrhotic chemical agents, carbon tetrachloride (CCl4) and thioacetamide (TAA). Methods and Results: Thioacetamide and CCl4 were administered to rats for 8 and 30 weeks, respectively before rats were killed and autopsies performed at 9, 20 and 30 weeks later. The TAA induced a fibrotic pattern in the liver that differed from that produced by CCl4, notably in the formation of fibrous connective tissue and the proliferation of bile ductule cells. Cholangiofibrosis and clear-cell foci were also observed in TAA-treated rats at 30 weeks. Histological examination revealed that severe cirrhotic changes were present 9 weeks after the commencement of CCl4 treatment and 30 weeks after TAA treatment. Discussion: When the subcellular redistribution of PKC isozymes (PKC,, -,1, -,, and -,) was examined, all the PKC isozymes in CCl4 -treated rats were found to be translocated to the membrane fraction, which may mean PKC activation, and then downregulated by proteolytic degradation after 9 weeks of treatment, which coincided with peak cirrhotic changes. All rats treated with CCl4 recovered to the control level after 20 weeks of treatment. In the case of TAA-treated rats, PKC isozymes were translocated to the particulate fraction of the liver after 9 weeks of treatment and this persisted in most of the rats for the duration of the experiment. Conclusions: From these results, it would appear that PKC translocation preceded morphologic changes, and that an altered subcellular distribution of the PKC isozyme may be associated with the response to liver damage and carcinogenesis. [source] Identification and properties of 2,5-Dihydroxy-4,3,-di(, - d -glucopyranosyloxy)- trans -stilbene from Morus bombycis Koidzumi rootsPHYTOTHERAPY RESEARCH, Issue 7 2007Ying-Shan Jin Abstract 2,5-Dihydroxy-4,3,-di(, - d -glucopyranosyloxy)- trans -stilbene was identified from Morus bombycis Koidzumi roots. The 2,5-dihydroxy-4,3,-di(, - d -glucopyranosyloxy)- trans -stilbene at a dose of 400,600 mg/kg had hepatoprotective activity comparable to the standard agent, silymarin. The biochemical assays were confirmed by histological observations showing that the 2,5-dihydroxy-4,3,-di(, - d -glucopyranosyloxy)- trans -stilbene from Morus bombycis Koidzumi roots decreased cell ballooning in response to CCl4 treatment. These results demonstrate that the 2,5-dihydroxy-4,3,-di(, - d -glucopyranosyloxy)- trans -stilbene component has a liver protective action against CCl4 -induced hepatotoxicity. Copyright © 2007 John Wiley & Sons, Ltd. [source] Changes of the hepatic proteome in murine models for toxically induced fibrogenesis and sclerosing cholangitisPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 24 2006Corinna Henkel Abstract We investigated the changes in the hepatic proteome in murine models for toxic-induced fibrogenesis and sclerosing cholangitis. A comprehensive comparison of protein changes observed is made and the mechanistical basis of the expression changes is discussed. Hepatic fibrosis was induced by repetitive intraperitoneal CCl4 treatment of BALB/c mice or developed spontaneously in BALB/c-ATP-binding cassette, subfamily B, member 4 (Abcb4) knock out mice. Fibrosis was verified by a morphometric score and assessment of hydroxyproline content of liver tissue, respectively. The innovative difference in-gel electrophoresis (DIGE) technique was used to analyse protein expression levels of the mouse proteome. Results were confirmed by Western blotting and real-time RT-PCR. In CCl4 -induced fibrosis 20 out of 40 and in BALB/c- Abcb4,/, mice 8 out of 28 differentially expressed proteins were identified utilizing DIGE. Only two proteins, selenium-binding protein (Sbp2) and carbonic anhydrase 3, have been unidirectionally expressed (i.e. down-regulated) in both models. Relevant differences in the pathogenesis of toxically induced liver fibrosis and sclerosing cholangitis exist. The only novel protein with regard to liver fibrosis depicting a unidirectional expression pattern in both animal models was Sbp2. An explicit protein function could not be clarified yet. [source] The effects of dietary flaxseed on the Fischer 344 rat.CELL BIOCHEMISTRY AND FUNCTION, Issue 6 2005Abstract The hepatotoxic effect of carbon tetrachloride (CCl4) administered by gavage at 0.25,ml CCl4 (1:1 in olive oil) per 100,g body weight was examined 24,h later in regular chow fed (RC) and 10% flax chow fed (FC) male and female Fischer 344 rats. CCl4 -treated RC rats were subdued, lethargic and unkempt. CCl4 -treated FC rats were much less affected. CCl4 treatment resulted in loss of weight in RC and FC rats. In males, the weight loss was 6.7% body mass in RC rats compared to 5.6% body mass in FC rats. In females, the weight loss was 7.5% body mass in both RC and FC rats. While CCl4 treatment increased the level of the liver injury marker plasma alanine aminotransferase (ALT) in RC rats, this CCl4 effect was significantly attenuated in FC rats. In male rats, the ALT increase was 435-fold in RC rats and 119-fold in FC rats, over that of their respective controls. In female rats, the ALT increase was 454-fold in RC rats and 381-fold in FC rats, over that of their respective controls. These results provide evidence that flax consumption protects the liver against injury and that the extent of the protection is sex dependent. CCl4 had no effect on the plasma level of ,-glutamyltranspeptidase (,GT) in RC and FC rats supporting the contention that plasma ,GT is not a useful marker for acute liver injury which is seen in this model. The activity of ,GT was increased in the livers of FC rats compared to RC rats: 2.7-fold in males and 1.5-fold in females. In RC rats, the activity of liver ,GT was decreased by CCl4 treatment: 70% in the male and 25% in the female. However, this CCl4 effect was reversed or abolished by flax consumption. Compared to RC rats: in male FC rats, CCl4 actually increased the activity of liver ,GT 1.28-fold; while in female FC rats, the depressing effect of CCl4 treatment was abolished. The flax-induced preservation of ,GT in the liver in response to injury may be involved in the observed hepatoprotection through generation of GSH. In RC male rats, CCl4 treatment effected a 25% reduction in plasma glucose levels. There was no decrease in CCl4 -treated FC male rats. In female rats, CCl4 treatment effected a 21% decrease in plasma glucose levels in both RC and FC rats. In conclusion, multiple parameters for acute CCl4 -induced injury were attenuated in the FC compared to the RC rat. That flaxseed consumption conferred greater protection against liver injury in the male than in the female suggests an involvement of the estrogenic lignan component of flaxseed. We discuss the possibility that this hepatoprotection is through a flax lignan-induced increase in reduced glutathione related to a flax effect on the activity of liver ,GT in the resting state and the maintenance of its activity in response to injury. Copyright © 2005 John Wiley & Sons, Ltd. [source] | ||||||||||