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Normal Rat Liver (normal + rat_liver)
Selected AbstractsUnique epithelial cell production of hepatocyte growth factor/scatter factor by putative precancerous intestinal metaplasias and associated "intestinal-type" biliary cancer chemically induced in rat liverHEPATOLOGY, Issue 6 2000Guan-Hua Lai Recently, we observed that Met, the receptor for hepatocyte growth factor/scatter factor (HGF/SF), is overexpressed in epithelial cells of both early-appearing intestinal metaplastic glands in precancerous hepatic cholangiofibrotic tissue and neoplastic glands in later developed intestinal-type of cholangiocarcinoma originated from the furan rat model of cholangiocarcinogenesis when compared with normal and hyperplastic intrahepatic biliary epithelia. We now show that HGF/SF is also aberrantly expressed in a manner closely paralleling that of its receptor in the neoplastic epithelial cells of furan-induced rat cholangiocarcinomas and in a majority of metaplastic epithelial cells within earlier formed precancerous hepatic cholangiofibrotic tissue. Using in situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR), we further showed specific expression of HGF/SF messenger RNA (mRNA) in a novel rat cholangiocarcinoma epithelial cell line overexpressing Met. This cholangiocarcinoma cell line, termed C611B, was established from tumorigenic cells isolated from a furan-induced transplantable tumor. Moreover, we detected by in situ hybridization strong expression of HGF/SF mRNA transcripts in the cancerous epithelial glands of cholangiocarcinoma developed in recipient rats after in vivo cell transplantation of C611B cells. In contrast, mRNA transcripts and protein immunoreactivity for this cytokine were not detected in hepatocytes and biliary epithelial cells in adult normal rat liver nor in rat hyperplastic intrahepatic biliary epithelium. Our results clearly show that HGF/SF becomes aberrantly expressed in cholangiocarcinoma epithelium and in putative precancerous intestinal metaplastic epithelium induced in the liver of furan-treated rats. [source] The lobular expression of the rat asialoglycoprotein receptor is regulated at the posttranscriptional levelLIVER INTERNATIONAL, Issue 1 2005Mara Massimi Abstract: The purpose of this study was to define the distribution of the asialoglycoprotein receptor (ASGP-R) main peptide, rat hepatic lectin (RHL)-1, within the rat liver lobule and to investigate its possible modulation in physiological states characterised by marked changes of receptorial expression. In particular, we chose livers from rats partially hepatectomised or at the end of pregnancy, as models, respectively, of decreased or increased expression of the ASGP-R, and used the in situ hybridisation and immunocytochemistry techniques to analyse in parallel the lobular distributions of RHL-1 mRNA and protein. In normal rat liver, although the RHL-1 mRNA was homogeneously distributed, the RHL-1 peptide was predominantly localised on the surface of pericentral hepatocytes with a gradient of expression towards the periportal zone. This gradient of expression of RHL-1 peptide was reduced in regenerating livers, in which the positive stain was restricted to a few layers of cells around the central vein. In contrast, livers at the end of pregnancy showed an overall increase of the peptide with a concomitant flattening of the gradient across the liver plate. In all the conditions, we never observed important changes in the pattern of expression of the specific mRNA. These findings indicate that the distribution of ASGP-R is heterogeneous across the liver lobule, with a pattern of expression prevalently modulated at the posttranscriptional level. [source] Effects of polyamines on DNA synthesis using various subcellular DNA polymerases extracted from normal rat liver, tumour-bearing rat liver, and tumour cellsCELL BIOCHEMISTRY AND FUNCTION, Issue 1 2001Takahiko Taguchi Abstract The effects of polyamines on DNA synthesis in vitro using various subcellular DNA polymerase fractions from normal and tumour-bearing rat livers, and tumour cells were investigated. When nuclear and mitochondrial DNA polymerase fractions were used, DNA synthesis on activated DNA was increased 3.5,8-fold by the addition of 20,mM putrescine or cadaverine. However, DNA synthesis was not stimulated by the addition of spermidine or spermine at any concentration tested. In contrast, DNA synthesis using the cytoplasmic DNA polymerase fraction was not stimulated at various concentrations of any of the four polyamines tested. The stimulatory effects of putrescine and cadaverine were absent when nuclear fractions from tumour-bearing rat liver or from tumour cells were used. In addition, in vitro DNA synthesis was not stimulated by 20,mM putrescine or cadaverine when nuclear extracts from the livers of rats administered putrescine subcutaneously were used. The specific activities of DNA polymerases extracted from tumour cells and tumour-bearing rat liver were already fully stimulated. These results suggest that DNA polymerases in tumour cells and tumour-bearing liver cells are stimulated by trapped putrescine produced in tumour cells and are thus no longer activated by exogenous putrescine. Copyright © 2001 John Wiley & Sons, Ltd. [source] A role for asymmetric dimethylarginine in the pathophysiology of portal hypertension in rats with biliary cirrhosis,,HEPATOLOGY, Issue 6 2005Wim Laleman Reduced intrahepatic endothelial nitric oxide synthase (eNOS) activity contributes to the pathogenesis of portal hypertension (PHT) associated with cirrhosis. We evaluated whether asymmetric dimethylarginine (ADMA), a putative endogenous NOS inhibitor, may be involved in PHT associated with cirrhosis. Two rat models of cirrhosis (thioacetamide [TAA]-induced and bile duct excision [BDE]-induced, n = 10 each), one rat model of PHT without cirrhosis (partial portal vein,ligated [PPVL], n = 10), and sham-operated control rats (n = 10) were studied. We assessed hepatic NOS activity, eNOS protein expression, plasma ADMA levels, and intrahepatic endothelial function. To evaluate intrahepatic endothelial function, concentration,effect curves of acetylcholine were determined in situ in perfused normal rat livers and livers of rats with TAA- or BDE-induced cirrhosis (n = 10) that had been preincubated with either vehicle or ADMA; in addition, measurements of nitrite/nitrate (NOx) and ADMA were made in perfusates. Both models of cirrhosis exhibited decreased hepatic NOS activity. In rats with TAA-induced cirrhosis, this decrease was associated with reduced hepatic eNOS protein levels and immunoreactivity. Rats with BDE-induced cirrhosis had eNOS protein levels comparable to those in control rats but exhibited significantly higher plasma ADMA levels than those in all other groups. In normal perfused liver, ADMA induced impaired endothelium-dependent vasorelaxation and reduced NOx perfusate levels, phenomena that were mimicked by NG -nitro- L -arginine-methyl ester. In contrast to perfused livers with cirrhosis induced by TAA, impaired endothelial cell-mediated relaxation in perfused livers with cirrhosis induced by BDE was exacerbated by ADMA and was associated with a decreased rate of removal of ADMA (34.3% ± 6.0% vs. 70.9% ± 3.2%). In conclusion, in rats with TAA-induced cirrhosis, decreased eNOS enzyme levels seem to be responsible for impaired NOS activity; in rats with biliary cirrhosis, an endogenous NOS inhibitor, ADMA, may mediate decreased NOS activity. (HEPATOLOGY 2005;42:1382,1390.) [source] Carbon monoxide produced by intrasinusoidally located haem-oxygenase-1 regulates the vascular tone in cirrhotic rat liverLIVER INTERNATIONAL, Issue 5 2009Lien Van Landeghem Abstract Background/Objective: Carbon monoxide (CO) produced by haem-oxygenase isoforms (HO-1 & HO-2) is involved in the regulation of systemic vascular tone. We aimed to elucidate the vasoregulatory role of CO in the microcirculation in normal and thioacetamide cirrhotic rat livers. Methods: Haem-oxygenase expression was examined by Western blot. Total HO enzymatic activity was measured spectrophotometrically. Sensitivity of hepatic stellate cells (HSCs) to CO-mediated relaxation was studied by a stress-relaxed-collagen-lattice model. To define the relative role of CO, the CO-releasing molecule CORM-2, the HO-inhibitor zinc protoporphyrin-IX and the HO-1 inducer hemin were added to an in situ liver perfusion set-up. The topography of vasoactive CO production was evaluated by applying different CO- and nitric oxide-trapping reagents in the liver perfusion set-up and by immunohistochemistry. Results: Western blot showed decreased expression of both HO isoenzymes (P<0.036 for HO-1; P<0.001 for HO-2) in cirrhotic vs normal rat livers, confirmed by the HO-activity assay (P=0.004). HSCs relaxed on exposure to CORM-2 (P=0.013). The increased intrahepatic vascular resistance (IHVR) of cirrhotic rats was attenuated by perfusion with CORM-2 (P=0.016) and pretreatment with hemin (P<0.001). Inhibition of HO caused a dose-related increase in IHVR in normal and cirrhotic liver. In normal liver, the haemodynamically relevant CO production occurred extrasinusoidally, while intrasinusoidally HO-1 predominantly regulated the microcirculation in cirrhotic livers. Conclusion: We demonstrate a role for CO and HO in the regulation of normal and cirrhotic microcirculation. These findings are of importance in the pathophysiology of portal hypertension and establish CO/HO as novel treatment targets. [source] | ||||||||||