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Time course of collagen peak in bile duct-ligated rats
Orhan Tarcin, Metin Basaranoglu, Veysel Tahan, Gülgün Tahan, Ilker Sücüllü, Nevin Yilmaz, Gagan Sood, Ned Snyder, Gilbert Hilman, Cigdem Celikel, Nurdan T?zün
BMC Gastroenterology , 2011, DOI: 10.1186/1471-230x-11-45
Abstract: Of the 53 male Wistar rats, 8 (Group 0) were used as a healthy control group. Bile duct ligation (BDL) had been performed in the rest. Bile duct-ligated rates were sacrificed 7 days later in group 1 (10 rats), 14 days later in group 2 (9 rats), 21 days later in group 3(9 rats) and 28 days later in group 4 (9 rats). Eight rats underwent sham-operation (Sham). Hepatic collagen measurements as well as serum levels of liver enzymes and function tests were all analysed.The peak level of collagen was observed biochemically and histomorphometricly at the end of third week (P < 0.001 and P < 0.05). Suprisingly, collagen levels had decreased with the course of time such as at the end of fourth week (P < 0.01 and P < 0.05).We have shown that fibrosis in bile duct-ligated rats is transient, i.e. reverses spontaneously after 3 weeks. This contrasts any situation in patients where hepatic fibrosis is progressive and irreversible as countless studies performed by many investigators in the same animal model.Hepatic fibrosis is characterized by massive deposition of extracelluler matrix components in the liver. There are differences on liver fibrogenesis due to etiological factors [1].Currently, there are no animal models that completely mimic the spectrum of the diseases seen in humans.One of the most useful experimental fibrosis models is the "bile duct-ligated rats". There is substantial information on morphological changes in the liver of the rats after obstructive jaundice to date. In 1932, Cameron et al. described gross macroscopic features and light microscopical changes in bile duct-ligated rats by intervals from 1/2 hour to 9 weeks [2]. Trams et al. in 1957 and Cameron et al. in 1958 studied functional and structural disturbances in the bile duct-ligated rats' liver [3,4]. Then, several investigators studied serum enzymes derived from liver cell fraction in the bile duct-ligated rat in 1972 [5]. Later studies investigated the effect of biliary obstruction on bile flow and
Effect of sirolimus on renal injury induced by bile duct ligation in rats
Ozturk, Hulya;Terzi, Akan;Ozturk, Hayrettin;Kukner, Aysel;
Acta Cirurgica Brasileira , 2010, DOI: 10.1590/S0102-86502010000500004
Abstract: purpose: to evaluate the effects of sirolimus (srl) on renal injury in rats with bile duct ligation. methods: a total of 21 male sprague-dawley rats weighing 220-260g were used. group 1 (sham-control, n=7) rats were undergone laparotomy alone and bile duct was just dissected from the surrounding tissue. group 2 rats (bdl/untreated, n=7) were subjected to bile duct ligation and no drug was applied. group 3 rats (bdl/srl, n =7) received a daily dose of sirolimus (0.5 mg·day-1xkg-1 dissolved 1 ml in saline) by orogastric tube for 14 days after bdl. at the end of the two-week period, biochemical and histological evaluation were processed. results: ast, alt, ap and tb levels values were decreased in group 3 when compared to group 2. there was no significant difference in serum levels of bun and creatinine among all the experimental groups. histological evaluation of the liver of bdl/untreated group rats demonstrated marked portal fibrosis and signs of major bile duct obstruction with prominent portal and lobular inflammation. in bdl/srl group, moderate damage was seen. tubular injury scores were higher in the bdl subgroups; however, group 3 rats showed considerably fewer lesions in the tubules and interstitium compared to the group 2 rats. in group 2 animals, in the epithelial cells of proximal tubules presented vacuoles and hydropic changes, atrophy and inflammatory cell infiltrate in the medullar interstitium. conclusions: sirolimus decreased tubulointerstitial lesions in kidney induced by bile duct ligation in rats. the improve effects of sirolimus on renal morphology can be due to improved liver function or due to direct action on the kidney.
Bile Duct Adenoma with Oncocytic Features  [PDF]
E. J. Johannesen,Zihao Wu,Jason-Scott Holly
Case Reports in Pathology , 2014, DOI: 10.1155/2014/282010
Abstract: Bile duct adenomas are benign bile duct proliferations usually encountered as an incidental finding. Oncocytic bile duct neoplasms are rare and the majority are malignant. A 61-year-old male with a diagnosis of colorectal adenocarcinoma was undergoing surgery when a small white nodule was discovered on the surface of the right lobe of his liver. This lesion was composed of cytologically bland cells arranged in tightly packed glands. These cells were immunopositive for cytokeratin 7, negative for Hep Par 1, contained mucin, and had a Ki67 proliferation index of 8%. The morphology, immunophenotype, presence of mucin, and normal appearing bile ducts, as well as the increased Ki67 proliferation rate, were consistent with a bile duct adenoma with oxyphilic (oncocytic) change. Oncocytic tumors in the liver are rare; the first described in 1992. Only two bile duct adenomas with oncocytic change have been reported and neither of them had reported mucin production or the presence of normal appearing bile ducts within the lesion. 1. Introduction Bile duct adenomas are benign proliferations of intrahepatic bile ducts. These lesions are usually found under the liver capsule, often as an incidental finding during surgery or at autopsy. Oncocytic bile duct neoplasms in the liver are very rare. Of the cases described, most have been cystic neoplasms with the majority being malignant. A bile duct adenoma with oncocytic features is an exceptionally rare lesion. Only two cases have thus far been reported. Here we report a case of a bile duct lesion with oncocytic features that has elements of a bile duct adenoma, as well as oncocytic and mucinous features. 2. Case Summary A 61-year-old male recently diagnosed with colorectal adenocarcinoma presented for resection of his tumor. A CT scan showed the large mass in the descending and sigmoid colon with several small lymph nodes in the mesocolon suspicious for metastatic disease. No abnormalities were identified in the liver, gallbladder, pancreas, or spleen. During surgery, a small white 0.3?cm diameter nodule was noted on the surface of the right lobe of the liver. Thought to be possible metastatic disease, this lesion was excised and sent for pathologic evaluation. Pathologic examination showed a well-circumscribed lesion composed of cytologically bland cells arranged in tightly packed glands with fibrous stroma. There was associated moderate chronic inflammation. The tumor did not invade the adjacent liver (Figure 1). No cystic spaces, bile duct dilation, or inspissated bile was identified. The neoplastic cells had small,
The Efficacy of Antioxidative Therapy in Hepatic Fibrosis Induced Experimentally by Bile Duct Ligation in Rats
Abdulmonem Al-Hayani
Journal of Animal and Veterinary Advances , 2012, DOI: 10.3923/javaa.2011.764.773
Abstract: Liver fibrosis which is a common result of chronic hepatic injury of diverse origins might be related to the occurrence of oxidative stress and accumulation of free radicals. It is characterized essentially by increased secretion and accumulation of different components Extracellular Matrix proteins (ECM). To investigate the beneficial effect of combined supplementation of vitamin E and selenium on hepatic fibrosis induced experimentally in bile duct-ligated rats. Forty albino rats were randomly assigned to 4 groups (10 rats in each); control group, sham-operated group Bile Duct-Ligated (BDL) group where the bile ducts of rats were ligated and BDL group co-treated with vitamin E and selenium where the rats underwent bile duct ligation and were fed with chow supplemented with vitamin E (250 mg kg-1) and selenium (0.2 mg kg-1 diet) starting from three days before the operation. At the end of 3rd week, the rats were sacrificed where blood was taken for biochemical estimations of serum enzymes and bilirubin. Fresh liver tissue was taken for determination of hydroxyproline content. Also, other liver samples of 5 mm3 were immediately fixed and processed for immunohistochemical demonstration of collagen type I and IV, fibronectin and laminin using the indirect immunoperoxidase method. Bile duct ligation resulted in a marked elevation in the levels of serum enzymes, bilirubin and hydroxyproline together with extensive bile duct proliferation. Strong staining was found for collagens I and IV, fibronectin and laminin in enlarged portal spaces around the newly formed bile ductuless. Co-treatment with vitamin E and selenium resulted in a shift in the serum enzymes, bilirubin and hydroxyproline towards the normal values. Also, a remarkable decrease of bile duct proliferation and in the intensity of staining for different ECM components in the portal spaces was observed. Antioxidants vitamins E and selenium combination attenuate the development of hepatic fibrosis in bile duct-ligated rats. Long-term, prospective studies in humans with chronic cholestatic liver diseases may be helpful to evaluate the beneficial effects of these elements.
Synchronous double cancers of the common bile duct  [cached]
Tatsuaki Sumiyoshi,Yasuo Shima,Akihito Kozuki
World Journal of Gastroenterology , 2012, DOI: 10.3748/wjg.v18.i41.5982
Abstract: We report an extremely rare case of synchronous double cancers of the common bile duct without pancreaticobiliary maljunction. Only two similar cases have been reported in the English literature. Endoscopic re-trograde cholangiopancreatography showed a tuberous filling defect in the middle and superior parts of the common bile duct, and mild stenosis in the inferior duct. Computed tomography (CT) showed a well enhanced mass in the middle and superior parts of the common bile duct. A single cancer of the middle and superior bile duct was suspected and extra-hepatic bile duct resection was performed. CT eleven months after surgery revealed enhanced inferior bile duct wall and a slightly enhanced tumor within it. Retrospective review of the CT images taken before first surgery showed enhanced inferior bile duct wall without intrabiliary tumor only on the delayed phase. The inferior bile duct tumor was suspected to have originally co-existed with the middle and superior bile duct tumor. Pancreaticoduodenectomy was performed subsequently. Histopathological examination revealed that the middle and superior bile duct tumor was a moderately differentiated tubular adenocarcinoma while the inferior bile duct tumor was a papillary adenocarcinoma. The two tumors were separated and had different histological findings and growth patterns, further suggesting that they were two primary cancers.
Development of hepatorenal syndrome in bile duct ligated rats  [cached]
Regina M Pereira, Robson AS dos Santos, Eduardo A Oliveira, Virgínia HR Leite, Filipi LC Dias, Alysson S Rezende, Lincoln P Costa, Lucíola S Barcelos, Mauro M Teixeira, Ana Cristina Sim?es e Silva
World Journal of Gastroenterology , 2008,
Abstract: AIM: To evaluate in bile duct ligated rats whether there were progressive alterations of renal function without changes in histopathology.METHODS: Male Wistar rats were submitted to sham-surgery or bile duct ligation (BDL) and divided according to the post-procedure time (2, 4 and 6-wk). To determine renal function parameters, rats were placed in metabolic cages and, at the end of the experiment, blood and urine samples were obtained. Histology and hydroxyproline content were analyzed in liver and renal tissue.RESULTS: Rats with 2 wk of BDL increased free water clearance (P = 0.02), reduced urinary osmolality (P = 0.03) and serum creatinine (P = 0.01) in comparison to the sham group. In contrast, rats at 6 wk of BDL showed features of HRS, including significant increase in serum creatinine and reductions in creatinine clearance, water excretion and urinary sodium concentration. Rats with 4 wk of BDL exhibited an intermediate stage of renal dysfunction. Progressive hepatic fibrosis according to post-procedure time was confirmed by histology. The increased levels of liver hydroxyproline contrasted with the absence of structural changes in the kidney, as assessed by histology and unchanged hydroxyproline content in renal tissue.CONCLUSION: Our data show that BDL produced progressive renal dysfunction without structural changes in the kidney, characterizing HRS. The present model will be useful to understand the pathophysiology of HRS.
Intraductal Papillary Neoplasms of the Bile Duct  [PDF]
Masayuki Ohtsuka,Hiroaki Shimizu,Atsushi Kato,Hideyuki Yoshitomi,Katsunori Furukawa,Toshio Tsuyuguchi,Yuji Sakai,Osamu Yokosuka,Masaru Miyazaki
International Journal of Hepatology , 2014, DOI: 10.1155/2014/459091
Abstract: Intraductal papillary neoplasm of the bile duct (IPNB) is a rare variant of bile duct tumors characterized by papillary growth within the bile duct lumen and is regarded as a biliary counterpart of intraductal papillary mucinous neoplasm of the pancreas. IPNBs display a spectrum of premalignant lesion towards invasive cholangiocarcinoma. The most common radiologic findings for IPNB are bile duct dilatation and intraductal masses. The major treatment of IPNB is surgical resection. Ultrasonography, computed tomography, magnetic resonance image, and cholangiography are usually performed to assess tumor location and extension. Cholangioscopy can confirm the histology and assess the extent of the tumor including superficial spreading along the biliary epithelium. However, pathologic diagnosis by preoperative biopsy cannot always reflect the maximum degree of atypia, because IPNBs are often composed of varying degrees of cytoarchitectural atypia. IPNBs are microscopically classified into four epithelial subtypes, such as pancreatobiliary, intestinal, gastric, and oncocytic types. Most cases of IPNB are IPN with high-grade intraepithelial neoplasia or with an associated invasive carcinoma. The histologic types of invasive lesions are either tubular adenocarcinoma or mucinous carcinoma. Although several authors have investigated molecular genetic changes during the development and progression of IPNB, these are still poorly characterized and controversial. 1. Introduction Intraductal papillary neoplasm of the bile duct (IPNB) is a rare variant of bile duct tumors, which is characterized by papillary or villous growth within the bile duct lumen. Formerly, attention has been drawn to biliary tumors with macroscopically visible mucin secretion, which show predominantly papillary growth within the dilated bile duct lumen and secrete a large amount of mucin. These tumors were called by various names, such as mucin-producing cholangiocarcinoma [1–4], mucin-hypersecreting bile duct tumor [5], and intraductal papillary mucinous tumor of the bile duct [6, 7], and were identified as a biliary counterpart of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. On the other hand, biliary intraductal tumors without macroscopically visible mucin secretion are also known, which have a macroscopically recognizable papillary or granular structure but no clinically visible mucin secretion. Since certain morphological features of these tumors, especially intraductal papillary growth pattern, are also similar to those of IPMN of the pancreas, Zen et al. [8] proposed
The Effects of Bile Duct Obstruction on Liver Volume: An Experimental Study  [PDF]
Bahtiyar Ertor,Serdar Topaloglu,Adnan Calik,Umit Cobanoglu,Ali Ahmetoglu,Huseyin Ak,Erdem Karabulut,Mithat Kerim Arslan
ISRN Surgery , 2013, DOI: 10.1155/2013/156347
Abstract: Objectives. This study is aimed at investigating alterations in liver volume during obstructive jaundice in rat liver. Materials and Methods. Thirty-six rats were divided into four groups. Abdominal tomography was performed for baseline volumetric analyses. The main bile ducts were ligated (BDL). Volumetric analyses were repeated 3 days after BDL in group 1, 7 days after BDL in group 2, 15 days after BDL in group 3, and 25 days after BDL in group 4, and total hepatectomy was performed in all animals. Control group ( ) was created with the rats that died before bile duct ligation. Results. There was no difference found in liver volume in group 1 compared to control animals. The liver volume was increased 7 days after BDL ( ). It was increased up to 60% of baseline values 25 days after BDL ( ). Wet liver weights of animals were also increased compared to control group. Liver weights were increased up to 40% percent of baseline values in group 4 ( ). Conclusions. Liver volume and weight were increased after BDL. Liver surgery in patients with huge liver mass is generally associated with significant difficulty. The surgeon should be aware of the time-dependent alteration in liver volume after obstructive jaundice. 1. Introduction Chronic cholestatic liver disease and bile duct tumors are the main causes of chronic cholestasis in daily clinical practice. Postcanalicular biliary obstruction leads to bile duct epithelial cell proliferation and periportal fibrosis [1–3]. Clinical and experimental studies have found that only the timely restoration of bile flow can halt fibrosis and reverse biliary hyperplasia [4–6]. The role of bile duct obstruction on liver volume has not been evaluated in detail. Thus, the aim of this study was to identify the time-dependent alterations on liver volume after bile duct ligation. 2. Materials and Methods Thirty-six male Sprague-Dawley rats weighing between 180 and 300?g were used for the study. They were kept under routine laboratory conditions and received standard laboratory chow with free access to food and water. The study protocol was approved by the institutional Ethics Committee for Experimental Studies at February 3, 2010, document number: 01/2010. 2.1. Experimental Design The animals were divided into four groups of 8 animals. Weight measurement and abdominal tomography under intraperitoneal ketamine (50?mg/kg, Ketalar, Parke-Davis, Ann Arbor, Michigan, USA) anesthesia for volumetric analyses were performed before bile duct ligation (BDL). In group 1 ( ), abdominal tomography (CT) was performed 3 days after BDL for
Hepatoprotective effect of Cocculus hirsutus on bile duct ligation-induced liver fibrosis in Albino Wistar rats
Sagar P. Thakare, Hitesh N. Jain, Savita D. Patil and Umesh M. Upadhyay
Bangladesh Journal of Pharmacology , 2009,
Abstract: In this animal model (Wistar rats of either sex) common bile duct was ligated for 28 days. Rats were treated for 28 days with methanol extract of Cocculus hirsutus. On day 29, blood and liver were collected for biochemical estimation and histopathological studies. Bile duct ligation produced liver fibrosis with generation of reactive oxygen species and induction of oxidative stress. Hence the different concentrations of methanolic extract of C. hirsutus were evaluated for in vivo glutathione reductase activity. On bile duct ligation the liver fibrosis was induced with significant rise in serum marker enzymes levels. The hydroxyproline accumulation caused by hydrophilic bile acids accompanied by elevated hepatic lipid peroxidation, and glutathione levels. Treatment with C. hirsutus extract decreased the elevated levels of serum marker enzymes showing hepatoprotection, which was further confirmed by histopathological results.
Effect of Bile Pigments on the Compromised Gut Barrier Function in a Rat Model of Bile Duct Ligation  [PDF]
Kangkang Zhou, Mingshan Jiang, Yuanli Liu, Yilin Qu, Guojing Shi, Xinguang Yang, Xiaofa Qin, Xiuhong Wang
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0098905
Abstract: Background Studies have shown that the absence of bile in the gut lumen, either by bile duct ligation or bile diversion, induces mucosal injury. However, the mechanism remains elusive. In this study, the role of bile pigments in gut barrier function was investigated in a rat model of bile duct ligation. Methods Male Sprague Dawley (SD) rats were used in this study. After ligation of bile duct, the animals were administrated with free bilirubin, bilirubin ditaurate, or biliverdin by intragastric gavage. 1, 2, or 3 days later, the animals were sacrificed and the damage of mucosa was assessed by histological staining as well as biochemical parameters such as changes of diamine oxidase (DAO) and D-lactate (D-Lac) in the blood. Trypsin and chymotrypsin of the gut were also measured to determine how these digestive proteases may relate to the observed effects of bile pigments. Results Bile duct ligation (BDL) caused significant increases in gut trypsin and chymotrypsin along with damage of the mucosa as demonstrated by the histological findings under microscope, the reduced expression of tight junction molecules like occludin, and significant changes in DAO and D-lac in the blood. Free bilirubin but not bilirubin ditaurate or biliverdin showed significant inhibitions on trypsin and chymotrypsin as well as alleviated changes of histological and biochemical parameters related to gut barrier disruption. Conclusion Bile may protect the gut from damage through inhibiting digestive proteases like trypsin and chymotrypsin by free bilirubin.
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