Hamster Gallbladder Research Articles

Alteration of sphingolipid metabolism and pSTAT3 expression by dietary cholesterol in the gallbladder of hamsters

Cholesterol and sphingolipids are major lipid constituents of the plasma membrane and have been implicated in a number of human diseases, such as atherosclerosis, fatty liver, diabetes mellitus, coronary heart disease, and hypertension. However, the relationship between cholesterol and sphingolipid metabolism has not been investigated. The purpose of this study was to determine whether dietary cholesterol would induce the alteration of sphingolipid metabolism in hamsters. Hypercholesterolemia was induced in hamsters by placing them on an experimental diet containing 0.5% cholesterol plus 0.5% choline chloride for 8 and 12 weeks. The serum profile of the hamsters showed that the administration of cholesterol increased the levels of total cholesterol, LDL cholesterol, and triglycerides as well as the activities of GOT and GPT. The levels of ceramide and sphingosine-1-phosphate (So-1-P) were remarkably elevated by 6-fold, respectively, in the bile juice of cholesterol-fed hamsters. Interestingly, the levels of iNOS and GFAP were increased in the gallbladders of cholesterol-fed hamsters. In addition, the immunostaining of pSTAT3 was increased on the gallbladder epithelium after cholesterol feeding. These results suggest that sphingolipid metabolism may be regulated in the bile juice during cholesterol feeding and may be a potential target for the treatment of hypercholesterolemia-induced diseases.

Inflammatory cytokines promote inducible nitric oxide synthase-mediated DNA damage in hamster gallbladder epithelial cells

To investigate the link between chronic biliary inflammation and carcinogenesis using hamster gallbladder epithelial cells. Gallbladder epithelial cells were isolated from hamsters and cultured with a mixture of inflammatory cytokines including interleukin-1beta, interferon-gamma, and tumor necrosis factor-alpha. Inducible nitric oxide synthase (iNOS) expression, nitric oxide (NO) generation, and DNA damage were evaluated. NO generation was increased significantly following cytokine stimulation, and suppressed by an iNOS inhibitor. iNOS mRNA expression was demonstrated in the gallbladder epithelial cells during exposure to inflammatory cytokines. Furthermore, NO-dependent DNA damage, estimated by the comet assay, was significantly increased by cytokines, and decreased to control levels by an iNOS inhibitor. Cytokine stimulation induced iNOS expression and NO generation in normal hamster gallbladder epithelial cells, which was sufficient to cause DNA damage. These results indicate that NO-mediated genotoxicity induced by inflammatory cytokines through activation of iNOS may be involved in the process of biliary carcinogenesis in response to chronic inflammation of the biliary tree.

Inflammatory cytokines promote inducible nitric oxide synthase-mediated DNA damage in hamster gallbladder epithelial cells

Inflammatory cytokines promote inducible nitric oxide synthase-mediated DNA damage in hamster gallbladder epithelial cells

Fatty acid bile acid conjugates (FABACs)—New molecules for the prevention of cholesterol crystallisation in bile

BACKGROUNDCholesterol gall stones are a frequent disease for which at present surgery is the usual therapy. Despite the importance of bile acids it has become evident that phospholipids are the...

Pathology, diagnosis and epidemiology of the rodent Helicobacter infection

Since the first isolation of Helicobacter pylori from humans in 1983, 18 Helicobacter species have been identified during the last decade in domestic and laboratory animals. Several Helicobacter species have been isolated from the gastrointestinal tracts of various mammalian species and birds. Helicobacter hepaticus, H. muridarum, H. bilis, H. rodentium and Flexispira rappini have been isolated from mice. Among these species, only H. hepaticus has been clearly recognized as a pathogen. Indeed, it displays the pathogenic potential to elicit hepatitis in several strains of mice; moreover in A/JCr mice, it is strongly associated with hepatic cancer. Among the five murine helicobacter species, apart from H. hepaticus, F. rappini has not been found associated with lesions, H. muridarum has been observed in gastric glands of mice with chronic gastritis, and H. bilis has been reported in the liver of mice with chronic hepatitis. When associated with H. rodentium, H. bilis is able to induce diarrhea in SCID mice. In no case has pathogenicity of a single species been clearly proven. In rats, H. trogontum and H. muridarum have been isolated from the intestine, without any information concerning their respective pathogenicity. H. cinaedi and H. cholecystus have been identified from the intestine and the gallbladders of hamsters, respectively. The diagnosis of Helicobacter species by polymerase chain reaction (PCR) is a rapid, specific and sensitive technique. One of the most promising diagnostic techniques of these infections seems to be the PCR detection of Helicobacter sp. from feces based on the 16S rRNA sequences, then a restriction enzyme analysis to identify the actual species. Several drug regimens have also been evaluated to eradicate H. hepaticus from mice. Helicobacter infections, particularly H. hepaticus and H. bilis, seem to be widespread in laboratory mouse colonies and have also been detected from commercial breeders.

Formation of black pigment gallstone in a hamster model of experimental cirrhosis.

The relationship between liver cirrhosis and the pathogenesis of black pigment stones has not been clarified. We attempted to induce black pigment stone formation in the gallbladders of hamsters. Male golden hamsters were divided into a cirrhosis group and a control group. Liver cirrhosis was induced by administering drinking water containing thioacetamide. The control group was given tap water. Gallstones at 48 weeks after treatment were examined by stereoscopic microscopy and scanning electron microscopy. The copper content of the black pigment stones was analysed by atomic absorption spectrophotometry. Black pigment stones in the gallbladder were detected in 25% of the cirrhosis group. Their surface and cross-section appeared amorphous. Black pigment stones contained copper. We confirmed the formation of gallstones in an animal model of cirrhosis by thioacetamide. Our findings may contribute to the clarification of the relationship between the pathogenesis of black pigment stones and the pathophysiology of liver cirrhosis.

Isolation of a novel Helicobacter species, Helicobacter cholecystus sp. nov., from the gallbladders of Syrian hamsters with cholangiofibrosis and centrilobular pancreatitis

A filamentous, gram-negative, motile bacterium with a single polar sheathed flagellum was isolated from gallbladders of hamsters with cholangiofibrosis and centrilobular pancreatitis. Bacteria grew under microaerophilic conditions at 37 and 42 degrees C, were oxidase, catalase, arginine aminopeptidase, and L-arginine arylamidase positive, reduced nitrate to nitrite, were resistant to cephalothin, and exhibited intermediate susceptibility to nalidixic acid. Sequence analysis of the 16S rRNA gene indicated that the bacterium was a novel member of the Helicobacter genus, most closely related to Helicobacter pametensis. We propose to name this bacterium Helicobacter cholecystus. In epidemiologic studies, isolation of H. cholecystus correlated strongly with the presence of cholangiofibrosis and centrilobular pancreatitis; however, further studies are needed to define the role of this bacterium in pathogenesis.

Effects of selenium on gallbladder carcinogenesis induced by an intracholecystic 3-methylcholanthrene beeswax pellet in female Syrian golden hamsters.

This study represents the first report of the effects of selenium (Se) on chemically induced gallbladder carcinogenesis in hamsters. A total of 100 female Syrian golden hamsters was randomly assigned to four groups, which groups of 25 hamsters were given ad libitum drinking water containing either 0.0, 0.5, 2.0 or 4.0 ppm Se (as sodium selenite) for 24 weeks. Initiation was performed at week 4 by the insertion of a Beeswax pellet containing 3-methylcholanthrene (3-MC) into the gallbladder. The incidence of total malignant tumors at the end of the study (24 weeks) was 88, 75, 81 and 82% in the 0.0, 0.5, 2.0 and 4.0 ppm Se groups, respectively. All the cases of carcinoma but two were considered to develop through the sequence from dysplasia to carcinoma in situ (CIS) and from CIS to adenocarcinoma of invasive type. The incidence of CIS was significantly lower in hamsters treated without Se than in those treated with Se (P < 0.05). On the other hand, the incidence of invasive adenocarcinoma was significantly higher in the former than in the latter (P < 0.05). These results were summarized that Se might retard the progression of hamster gallbladder carcinogenesis induced by a 3-MC beeswax pellet.

Magnetic resonance imaging for the visualization of cholesterol gallstones in hamster fed a new high sucrose lithogenic diet

Cholesterol gallstone induction in hamster gallbladder is usually achieved by specific diets. An X-ray in vivo follow-up of cholelithiasis development in this species is impossible, since cholesterol gallstones are transparent as long as they are not calcified. Moreover, their size (0.2 to 1 mm) also prevents their detection by ultrasonography. The current study presents an in vivo cholesterol gallstone detection by magnetic resonance imaging in hamsters fed a new high sucrose diet containing a low proportion of cholesterol (0.015%) and a normal ratio of lipids (10%). The diet produced gallstones and an increase in the cholesterol saturation index in about 50% of animals after a 5-week feeding period. The visualization of gallstones by magnetic resonance imaging in anaesthetized animals required synchronization between breathing movements and image acquisition. A high magnetic field was also necessary to allow a fine image resolution, adapted to gallstone size. Two major advantages of this technique are a direct selection of lithiastic animals with a functional gallbladder (in spite of the presence of gallstones) and a possible adjustment of the treatment period of potential litholytic drugs.

Cytometric study of the female Syrian hamster gallbladder epithelium following sex steroid administration

This report is a cytometric study of the female Syrian hamster gallbladder epithelium following 1-, 2-, and 3-month administration of female sex steroids. Nulliparous, multiparous, young, old and pregnant hamsters were used in this study. A 1 month treatment with estrogen alone significantly increases the nuclear volume of the gallbladder epithelial cells, while E + P treatment significantly affects the nuclear volume only after a 2 month treatment. On the other hand, E + P and P treatments significantly increase the cell volumes as compared to the E-treated groups, this effect is most striking following the 1 month period. Prolonged sex steroid treatment (2 and 3 month) does not appear to influence the gallbladder epithelial cell and nuclear volumes as dramatically as that observed following the 1 month treatment. The nulliparous, progesterone-treated hamsters appear to have a greater cytoplasmic volume than the multiparous group and this is substantiated by the bulging apices and the luminal cellular excrescences observed with scanning and transmission electron microscopy. These observations are similar to those reported in ovariectomized hamsters (Gilloteaux et al., 1992). Further, the gallbladder epithelial cells and nuclei of the older female hamsters demonstrate an accentuated response to a 1 month sex steroid treatment as compared to the younger hamsters for the same treatment duration. These results enable us to hypothesize that changes induced by a short term sex steroid treatment participate in the gallstone nucleation process, while longer duration of the treatments contribute to progressive enlargement and accumulation of gallbladder calculi.

Apical excrescences in the gallbladder epithelium of the female Syrian hamster in response to medroxyprogesterone.

All the intact female Syrian hamsters treated with medroxyprogesterone (MP) for a one-month period, without dietary manipulation, display gallbladder surface epithelial changes, and intraluminal deposits. These changes include excrescences in various stages, bulging, and extrusion of material from the epithelial cells. The most striking scanning electron microscopic observations are the dramatic events, comparable to apocrine-like secretory events observed in another related study using oophorectomized hamsters. Since the hamster gallbladder does not possess mucous goblet cells, it appears that this phenomenon could be a response to the MP treatment, thus providing a larger amount of mucous product than usual with cellular material, in addition to the possible alteration in the quality of the bile following this treatment. As a result of MP treatment, intraluminal deposits were also confirmed by using light and transmission electron microscopy. In control hamsters these events were not observed, however, small blebs outlining surface epithelial cells are seen. The results in this report complement the previous studies using the male and oophorectomized Syrian hamster model subjected to similar experimental conditions.

3,2′‐Dimethyl‐4‐aminobiphenyl‐induced Gallbladder Carcinogenesis and Effects of Ethinyl Estradiol in Hamsters

The effects of ethinyl estradiol (EE) on 3,2′‐dimethyl‐4‐aminohiphenyl (DMAB)‐induced carcinogenesis were examined in Syrian golden hamsters. DMAB was subcutaneously injected in corn oil at a concentration of 100 mg/kg once a week for 20 weeks and EE was administered in the diet at a dose of 0.75 ppm throughout the experiment. Some animals were killed at week 20 and ail surviving ones were killed at week 50. Gallbladder tumors (adenomas and carcinomas) were induced in 6 of 15 hamsters (40%) in the DMAB + EE group and 5 of 14 (36%) in the DMAB alone group in males, and in 6 of 13 (46%) in the DMAB + EE group and 1 of 8 (13%) in the DMAB alone group in females at week 50. A clearer enhancing effect of EE on DMAB gallbladder carcinogenesis was observed for tumor multiplicity (No./animal) for both sexes; from 0.36 to 0.67 in males and from 0.14 to 0.62 in females. Thus, DMAB was demonstrated to be carcinogenic in the gallbladder of hamsters and EE enhanced this DMAB‐induced gallbladder tumorigenesis.

Radiographic evidence of cholecystokinin octapeptide receptors in the hamster gallbladder

Radiographic evidence of cholecystokinin octapeptide receptors in the hamster gallbladder

Effects of acute stress (water immersion restreint, fasting) on mucus hypersecretion of the hamster gallbladder epithelium. A quantitative electron microscopic study

Effects of acute stress (water immersion restreint, fasting) on mucus hypersecretion of the hamster gallbladder epithelium. A quantitative electron microscopic study

Biliary-hepatic recycling of a xenobiotic: gallbladder absorption of methyl mercury

The role of the gallbladder in the disposition of methyl mercury was investigated in guinea pig, hamster, and macaque monkey. 203Hg-labeled methyl mercury or inorganic mercury (5 microM) and [14C]inulin were instilled into the in situ guinea pig or hamster gallbladder. After 2 h, only 27.6 +/- 7.0% of the methyl mercury remained in guinea pig gallbladder fluid as compared with 85.0 +/- 3.2% of the inorganic mercury and 90.7 +/- 4.5% of the [14C]-inulin. In the hamster, 42.5 +/- 4.5% of methyl mercury and 95% +/- 0.9% of inorganic mercury remained after 2 h. When the sulfhydryl-containing compounds L-cysteine, glutathione, and bovine serum albumin (20 microM) were added to the test solution, cysteine increased and albumin decreased absorption of methyl mercury. Ligation of guinea pig cystic artery decreased gallbladder fluid absorption from 72.7 +/- 8.6 to 26.5 +/- 9.8% over 2 h but did not alter methyl mercury absorption. Bile was also sampled from gallbladders of four monkeys exposed chronically to CH3HgCl and from three control monkeys. For one of the exposed and one of the control monkeys, bile was also collected from the common hepatic duct. In both methyl mercury-exposed and control monkeys, the concentration of methyl mercury in gallbladder bile was lower than in hepatic bile. In contrast, the concentration of inorganic mercury in gallbladder bile was four to seven times that of hepatic bile, suggesting that methyl mercury but not inorganic mercury was being reabsorbed. To assess the functional significance of methyl mercury reabsorption by the gallbladder, guinea pig cystic ducts were ligated, the animals were given CH3 203HgCl (10 mumol/kg iv), and body burden of 203Hg was measured over 16 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental Obliterative Gholangitis A Model for the Study of Biliary Atresia

Noninfectious obliterative cholangitis results from biliary tract inflammation in clinical conditions such as biliary atresia and sclerosing cholangitis. The purpose of this study was to develop an animal model of noninfectious biliary tract inflammation and fibrosis. An implantable osmotic pump was connected to a catheter placed into the gallbladder of hamsters. Phorbol myristate acetate (PMA) was infused into the biliary tract for periods of 6 hours to 28 days. After 7 days the animals developed neutrophil infiltration, cellular necrosis, and edema of the biliary ducts. After 14 days, the animals demonstrated intrahepatic cholestasis with bile duct fibrosis and acute and chronic inflammatory cell infiltration. By 28 days pronounced portal fibrosis was present, some of which created an early bridging cirrhosis pattern. In addition there was evidence of neocholangiogenesis. We conclude that long-term PMA infusion into the biliary tract generates an inflammatory response characterized by obliterative cholangitis and fibrosis, sharing many of the histologic features of human biliary atresia. This model may provide a relatively simple technique for investigating the process of nonpyogenic biliary tract inflammation.

Radiographic Evidence of Cholecystokinin Octapeptide Receptors in the Hamster Gallbladder

The distribution of cholecystokinin receptors in the hamster gallbladder was investigated by 125I-labeled Bolton-Hunter-cholecystokinin octapeptide autoradiography. Light microscopic examination showed a marked accumulation of radiolabeled cholecystokinin within the domain of the muscle layer of the gallbladder. The electron microscopic study further disclosed the presence of radiolabeling mostly in those areas corresponding to cell-to-cell junctions of smooth-muscle cells. Our results suggest that contraction of the gallbladder may primarily be induced by cholecystokinin interacting with its specific receptor in smooth-muscle cells. That cholecystokinin receptors were more abundant in the junctional complexes of smooth-muscle cells suggests that cholecystokinin may have a major role in muscle contraction of the gallbladder, which eventually produces an effective bile emptying.

Morphological changes of the hamster gallbladder in the contracted and distended states

Morphological changes of the hamster gallbladder in the contracted and distended states

Gallbladder mucin glycoprotein hypersecretion in experimental cholelithiasis: role of mucin gel in nucleation of cholesterol gallstones.

The emphasis of gallstone research in the past decade has focused on the role of cholesterol supersaturation in bile and reduction in bile salt pool size in the pathophysiology of cholelithasis. However it is now recognized that cholesterol supersaturation is a frequent finding in normal individuals (1), and that a nucleation factor (2) is present in lithogenic gallbladder bile. Womack (3) first suggested that gallbladder mucus glycoproteins could serve as a nucleating agent for cholesterol stones, and noted that nucleation of cholesterol crystals occured in mucus aggregates in the gallbladder of hamsters fed a lithogenic diet. Increased concentrations of gallbladder mucus glycoproteins has been described in experimental cholelithiases in rabbits (4) and dogs (5) and in gallbladder bile from patients with cholesterol stones. (6) Analysis of human gallstones reveals the presence of mucus glycoproteins which may form a matrix for the stones. (7)KeywordsCholesterol GallstoneCholesterol CrystalHepatic BileGallbladder BileCholesterol StoneThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

The Minute Structure of the Hamster Gallbladder with Special Reference to the Functions of the Epithelium

The Minute Structure of the Hamster Gallbladder with Special Reference to the Functions of the Epithelium