The application of Compont gel in chronic obstructive jaundice rats model

Abstract Purpose: To establish a new rat model, the pathogenesis of which is closer to the clinical occurrence of chronic obstructive jaundice with liver fibrosis. Methods: 90 SD rats were randomly divided into 3 groups. Group A common bile duct ligation, group B common bile duct injection compont and group C injection saline. The serum of three groups was extracted, and the liver function was detected by ELISA. HE staining, Masson staining and immunohistochemistry were used to detect liver pathology. Results: Group B showed a fluctuant development of jaundice, obstructive degree reached a peak at 2 weeks, and decreased from 3 weeks. HA, LA and PCIII were significantly higher than control group. 3 weeks after surgery, liver tissue fibrosis occurred in group B, and a wide range of fiber spacing was formed at 5 weeks. Immunohistochemistry showed that hepatic stellate cells were more active than the control group. Conclusion: Intra-biliary injection of Compont gel is different from the classic obstructive jaundice animal model caused by classic bile duct ligation, which can provide an ideal rat model of chronic obstructive jaundice with liver fibrosis.

NAFLD e ingesta de fructosa en altas concentraciones: una revisión de la literatura / NAFLD and high fructose intake: a review of literature

Uno de los endulzantes más comúnmente utilizado es la fructosa. La fructosa es directamente metabolizada en el hígado y se puede transformar en glucosa, posteriormente es almacenada como glicógeno constituyéndose en una fuente de energía para los hepatocitos. Todo el exceso de fructosa se convierte en lípidos ejerciendo un efecto tóxico sobre el hígado, similar al producido por el exceso de alcohol, pudiendo provocar hígado graso no alcohólico (NAFLD). El objetivo de esta revisión es reunir hallazgos recientes en relación al efecto de la ingesta de fructosa en altas concentraciones y su relación con el NAFLD.

One of the most commonly used sweeteners is fructose. Fructose is directly metabolized in the liver and can be converted into glucose, later stored as glycogen constituting a source of energy for the hepatocytes. All excess fructose is converted into lipids by exerting a toxic effect on the liver, similar to that produced by excess of alcohol, and can cause nonalcoholic fatty liver (NAFLD). The aim of this review is to gather recent findings regarding the effect of fructose intake at high concentrations and its relationship with NAFLD.

Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment

OBJECTIVES: The present study was designed to evaluate the bone phenotypes and mechanisms involved in bone disorders associated with hepatic osteodystrophy. Hepatocellular disease was induced by carbon tetrachloride (CCl4). In addition, the effects of disodium pamidronate on bone tissue were evaluated. METHODS: The study included 4 groups of 15 mice: a) C = mice subjected to vehicle injections; b) C+P = mice subjected to vehicle and pamidronate injections; c) CCl4+V = mice subjected to CCl4 and vehicle injections; and d) CCl4+P = mice subjected to CCl4 and pamidronate injections. CCl4 or vehicle was administered for 8 weeks, while pamidronate or vehicle was injected at the end of the fourth week. Bone histomorphometry and biomechanical analysis were performed in tibiae, while femora were used for micro-computed tomography and gene expression. RESULTS: CCl4 mice exhibited decreased bone volume/trabecular volume and trabecular numbers, as well as increased trabecular separation, as determined by bone histomorphometry and micro-computed tomography, but these changes were not detected in the group treated with pamidronate. CCl4 mice showed increased numbers of osteoclasts and resorption surface. High serum levels of receptor activator of nuclear factor-κB ligand and the increased expression of tartrate-resistant acid phosphatase in the bones of CCl4 mice supported the enhancement of bone resorption in these mice. CONCLUSION: Taken together, these results suggest that bone resorption is the main mechanism of bone loss in chronic hepatocellular disease in mice.

Inhibitory effect of liposomal quercetin on acute hepatitis and hepatic fibrosis induced by concanavalin A

Immune response plays an important role in the development of hepatic fibrosis. In the present study, we investigated the effects of quercetin on hepatitis and hepatic fibrosis induced by immunological mechanism. In the acute hepatitis model, quercetin (2.5 mg/kg) was injected iv into mice 30 min after concanavalin A (Con A) challenge. Mice were sacrificed 4 or 24 h after Con A injection, and aminotransferase tests and histopathological sections were performed. Treatment with quercetin significantly decreased the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Consistent with this observation, treatment with quercetin markedly attenuated the pathologic changes in the liver. A hepatic fibrosis model was also generated in mice by Con A challenge once a week for 6 consecutive weeks. Mice in the experimental group were treated with daily iv injections of quercetin (0.5 mg/kg). Histopathological analyses revealed that treatment with quercetin markedly decreased collagen deposition, pseudolobuli development, and hepatic stellate cells activation. We also examined the effects of quercetin on the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transforming growth factor beta (TGF-β) pathways by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR). NF-κB and TGF-β production was decreased after treatment with quercetin, indicating that the antifibrotic effect of quercetin is associated with its ability to modulate NF-κB and TGF-β production. These results suggest that quercetin may be an effective therapeutic strategy in the treatment of patients with liver damage and fibrosis.

Cirrhosis in rats does not resolve in the long-term after induction by thioacetamide model

Introductions: Hepatic cirrhosis is a final common pathway of all chronic liver diseases, characterized by deposit of fibrillar collagen and liver failure. Materials and Methods: In this experiment, hepatic cirrhosis was induced in 15 female Wistar rats by a 14-week period, with thioacetamide solution in a 200 mg/kg dosage, via intraperitoneal. Animals were submitted to liver biopsy, and euthanized after a 80-day post-induction period. Serum biochemical analysis was performed, in addition to histopathology by H.E., Picrosirius, Alcian Blue and P.A.S. stainings, following analysis of histological activity index and staging of fibrosis. Morphometric analysis of collagen on Picrosirius slides was also performed. Results: Mortality during experimental period was low (13.33%), and after 80-day period, liver function improved, cellular changes did not altered, and deposition of acidic mucopolysaccharides and glycogen were increased. Liver histological activity did not change significantly (7.25 ± 1.30 to 6.41 ± 1.32), but staging of fibrosis was altered (3.91 ± 0.76 to 4.70 ± 1.11). Interlobular collagen showed a significant decrease (5.14 ± 2.00 to 4.00 ± 1.20), while intralobular collagen was increased (0.23 ± 0.06 to 0.36 ± 0.08). Conclusions: These findings characterize thioacetamide as a safe experimental model for induction cirrhosis, which may be used for future therapy studies.(AU)

A reduced grade of liver fibros-steatosis after raltegravir, maraviroc and fosamprenavir in an HIV/HCV co-infected patient with chronic hepatitis, cardiomyopathy, intolerance to nelfinavir and a marked increase of serum creatine phosphokinase levels probably related to integrase inhibitor use / Grado reducido de fibroesteatosis tras la administración de raltegravir, maraviroc y fosamprenavir en un paciente co-infectado de VIH/VHC con hepatitis crónica, cardiomiopatía, intolerancia al nelfinavir y un aumento pronunciado de los niveles de creatina fosfoquinasa sérica probablemente debido al uso del inhibidor de la integrasa

The use of new antiretroviral drugs in HIV infection is particularly important in patients with intolerance or resistance to other antiretroviral agents. Raltegravir and maraviroc represent new, important resources in salvage regimens. A reduced grade of liver fibro-steatosis after a combination of raltegravir and maraviroc (second-line) has not been studied and the mechanism by which these new drug classes induced a marked reduction of grade of liver diseases is currently unknown. In the present case report, nested in an ongoing multicentre observational study on the use of new antiretroviral inhibitors in heavy treatment-experienced HIV patients, we evaluated the correlation between a "short therapeutic regimen" raltegravir, maraviroc and fosamprenavir and liver diseases. The aim of this report is to describe the use of a three-drug regimen based on two novel-class antiretroviral agents (raltegravir and maraviroc) plus the protease inhibitor fosamprenavir, in an experienced HIV-infected patient with chronic progressive hepatitis C complicated by liver fibrosis; an overwhelming increased serum creatine kinase level occurred during treatment, and is probably related to integrase inhibitor administration. At present no information is available regarding this correlation.

El uso de nuevos medicamentos antiretrovirales para la infección por VIH es particularmente importante en los pacientes con intolerancia o resistencia a otros agentes antiretrovirales. Raltegravir (RTV) y maraviroc (MRV) representan nuevos e importantes recursos en las terapias de salvamento. Un grado reducido de fibroesteatosis hepática después de una combinación de raltegravir y maraviroc (terapia de segunda línea) no ha sido estudiado, y el mecanismo por el cual estas nuevas clases de droga indujeron una marcada reducción de grado de las enfermedades hepáticas se desconoce hasta el momento. Como parte de la realización en curso de un estudio observacional multicentro acerca del uso de nuevos inhibidores antiretrovirales en pacientes de VIH altamente experimentados en el tratamiento, en el presente reporte de caso se evalúa la correlación entre un "régimen terapéutico corto" (raltegravir, maraviroc y fosamprenavir) y las enfermedades del hígado. El objetivo de este reporte es describir el uso de un régimen de tres medicamentos - basado en dos agentes antiretrovirales de nuevo tipo (raltegravir y maraviroc) además del fosamprenavir inhibidor de la proteasa - en un paciente de VIH experimentado. El paciente también sufre de hepatitis C evolutiva, progresiva, crónica, complicada por fibrosis hepática. Durante el tratamiento, se produjo un aumento extraordinario del nivel de creatina quinasa sérica, el cual probablemente esta relacionado con la administración del inhibidor de la integrasa. Actualmente no hay información disponible con respecto a esta correlación.

Parthenolide-induced apoptosis of hepatic stellate cells and anti-fibrotic effects in an in vivo rat model

Parthenolide (PT), a sesquiterpene lactone derived from the plant feverfew, has pro-apoptotic activity in a number of cancer cell types. We assessed whether PT induces the apoptosis of hepatic stellate cells (HCSs) and examined its effects on hepatic fibrosis in an in vivo model. The effects of PT on rat HSCs were investigated in relation to cell growth inhibition, apoptosis, NF-kappaB binding activity, intracellular reactive oxygen species (ROS) generation, and glutathione (GSH) levels. In addition, the anti-fibrotic effects of PT were investigated in a thioacetamide-treated rat model. PT induced growth inhibition and apoptosis in HSCs, as evidenced by cell growth inhibition and apoptosis assays. PT increased the expression of Bax proteins during apoptosis, but decreased the expression of Bcl-2 and Bcl-XL proteins. PT also induced a reduction in mitochondrial membrane potential, poly(ADP-ribose) polymerase cleavage, and caspase-3 activation. PT inhibited TNF-alpha-stimulated NF-kappaB binding activity in HSCs. The pro-apoptotic activity of PT in HSCs was associated with increased intracellular oxidative stress as evidenced by increased intracellular ROS levels and depleted intracellular GSH levels. Furthermore, PT ameliorated hepatic fibrosis significantly in a thioacetamide-treated rat model. In conclusion, PT exhibited pro-apoptotic effects in rat HSCs and ameliorated hepatic fibrosis in a thioacetamide-induced rat model.

Distribution of Hepatic Myofibroblasts and Type I and III Collagen in Rat Liver Cirrhosis Induced by Thioacetamide / Distribución de Miofibroblastos y Colágeno Tipo I y III en Hígado de Ratas con Cirrosis Inducida por Tioacetamida

Thioacetamide (TAA) can induce various types of cirrhosis in the rat, including bridging fibrosis, biliary fibrosis, perisinusoidal/pericellular fibrosis and centrilobular fibrosis, in which different populations of hepatic myofibroblasts (MFs) are involved. The hepatic MFs can be classified into 3 groups: (a) portal/septal MFs; (b) activated hepatic stellate cell myofibroblasts (HSC/MFs); and (c) interface myofibroblasts (IF/MFs). The present study was carried out to examine the morphology and localization of hepatic MFs in relation to the distribution of type I and III collagen in rat cirrhotic livers. Immunohistochemistry to a-smooth muscle actin was employed to demonstrate the morphology and localization of the subpopulations of hepatic MFs. The distribution of type I and III collagen was investigated by using specific antibodies. Portal and septal MFs were windmill in shape and localized around tributaries of the portal and hepatic veins where type I and III collagen was accumulated. HSC/MFs with arachnoid in shape were localized in the spaces of Disse and spaces between neighboring hepatocytes where type I collagen was formed. IF/MFs showed arachnoid shapes and distributed along the margin of fibrous septa where type I collagen was condensed. MFs with polygonal shapes were also found around the wall of hepatic sinusoids, margin of fibrous septa and around the portal tract. They were probably transitional cells to the mature MFs. Our data suggest that each subpopulation of hepatic MFs shows characteristic morphology and localization, which correlates with localization of type I and/or type III collagen.

La tioacetamida (TAA) puede provocar diversos tipos de cirrosis hepática en la rata, incluyendo fibrosis en puente, fibrosis biliar, fibrosis perisinusoidal/pericelular y fibrosis centrolobulillar, en los que diferentes poblaciones de miofibroblastos hepáticos (MFs) están involucrados. Los MFs hepáticos se pueden clasificar en tres grupos: (a) MFs portal/ septal; (b) células estrelladas hepática activada miofibroblásticas (HSC/MFs), y (c) miofibroblastos de interface (IF/MFs). El presente estudio se realizó para examinar la morfología y localización de los MFs hepáticos en relación con la distribución de colágeno Tipos I y III en el hígado de ratas cirróticas. Se utilizó inmunohistoquímica de a-actina de músculo liso para demostrar la morfología y localización de las subpoblaciones de MFs hepática. La distribución de colágenos Tipos I y III se investigó utilizando anticuerpos específicos. FMs portales y septales mostraron forma de molino de viento y se localizaron cerca de afluentes de las venas porta y hepática donde los colágenos Tipos I y III se acumularon. HSC/MFs con forma aracnoide se localizaron en los espacios de Disse y los espacios entre hepatocitos vecinos, donde se formó el colágeno Tipo I. IF/MFs mostraron formas aracnoides y se distribuyeron a lo largo del margen de los septos fibrosos donde se condensó el colágeno Tipo I . MFs con formas poligonales también fueron encontrados alrededor de la pared de los sinusoides hepáticos, en el margen de los septos fibrosos y en todo el tracto portal. Probablemente fueron células de transición a los MFs maduros. Nuestros datos sugieren que cada subpoblación de MFs hepáticos muestra una morfología y localización característica, que se correlaciona con la localización de colágenos Tipo I y o III.

Suppression of hepatic tumor growth and metastasis by metronomic therapy in a rat model of hepatocellular carcinoma

Although continuous low-dose (metronomic [MET]) therapy exerts anti-cancer efficacy in various cancer models, the effect of long-term MET therapy for hepatocellular carcinoma (HCC) remains unknown. This study assessed the long-term efficacy of MET on suppression of tumor growth and spontaneous metastasis in a rat model of HCC induced by administration of diethylnitrosamine for 16 wk. The rats were divided into 3 groups: MTD group received intraperitoneal (i.p.) injections of 40 mg/kg cyclophosphamide on days 1, 3, and 5 of a 21-day cycle; Control and MET groups received i.p. injections of saline and 20 mg/kg cyclophosphamide twice a week, respectively. Anti-tumor and anti-angiogenic effects and anti-metastatic mechanisms including matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) were evaluated. Twelve wk of MET therapy resulted in a significant reduction in intrahepatic tumors than control or MTD therapy. The MET group had fewer proliferating cell nuclear antigen-positive cells and decreased hypoxia-inducible factor-1alpha levels and microvessel density. Lung metastases were detected in 100%, 80%, and 42.9% in the control, MTD, and MET groups, respectively. MET therapy significantly decreased expression of TIMP-1, MMP-2 and -9. For mediators of pro-MMP-2 activation, MET therapy induced significant suppression in the TIMP-2 and MMP-14 level. The survival in the MET group was significantly prolonged compared to the control and MTD groups. Long-term MET scheduling suppresses tumor growth and metastasis via its potent anti-angiogenic properties and a decrease in MMPs and TIMPs activities. These results provide a rationale for long-term MET dosing in future clinical trials of HCC treatment.

Hepatic oval cells activated by hepatocyte apoptosis in diethylnitrosamine-induced rat liver cirrhosis

To investigate whether hepatic oval cells are activated in diethylnitrosamine [DEN]-induced rat liver cirrhosis, and to explore its mechanism. Liver cirrhosis was induced in rats [n=8] by weekly intraperitoneal injections of DEN at a dose of 50mg/kg body weight for 12 weeks followed by a 2-week wash out period. Rats [n=5] that received isovolumic vehicle served as the control group. Liver pathology was examined. Apoptotic hepatocytes were identified and quantified by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling [TUNEL] assay. Oval cells were detected using immunohistochemical staining for pyruvate kinase type M2 [M2PK] and cytokeratin 19 [CK19]. The work was carried out at Renmin Hospital of Wuhan University, Wuhan, Hubei, China from February to December 2009. Liver cirrhosis developed in rats subjected to DEN administration. The TUNEL and morphology assay showed that a substantial number of hepatocytes underwent apoptosis. The apoptotic index in rats subjected to DEN administration [0.75 +/- 0.15] was much higher than normal control rats [0.10 +/- 0.05]. Both CK19 and M2PK were moderately expressed in the rat liver cirrhosis, and the expression was dispersed or forming small cords in the liver; but the expression was hardly detected in the liver tissue of normal control rats. In the DEN-induced rat liver cirrhosis, oval cells are activated and stimulated to proliferation, the mechanism of which may be related to substantial hepatocyte apoptosis in the model

Therapeutic potential of mouse bone marrow mesenchymal stem cells in carbon tetrachloride [CCI[4]]-lnduced liver fibrosis

To study the effect of allogenic bone marrow mesenchymal stem cells [BMMSCs] transplantation on carbon tetrachloride-induced liver fibrosis in mice. Fifty five female NMRI mice were divided in 5 groups, and to induce liver fibrosis CCL[4] intraperitonealy was injected 1 ml/Kg twice a week for 8 weeks 10[6] allogenic BMMSCs were infused in cell therapy group via tail vain at the end of 4[th] weeks. Liver samples were taken and evaluated with histopathologic and immunofluorescence techniques to determine the amount of fibrosis, cell homing and identity of the cells. Mice serum albumin level was measured as well. In the cell therapy group the amount of liver fibrosis and mortality rate decreased significantly [2.24 +/- 0.51% vs 3.48 +/- 0.6%, PO.05 and 27.3% vs 45.5%], respectively but there was no significant difference between their serum albumin level. These results were in compliance with low proportion of transplanted cells capable of producing albumin [0.23 +/- 0.08% of liver cells]. Because most transplanted cells were found in periportal area; they did not produce albumin. Conclusion: It seems that the major role of BMMSCs to reduce CCL[4]-induced liver fibrosis does not occur by their differentiation into hepatocyte but rather through other interaction pathways with injured liver tissue

Differential Expression of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Thioacetamide-Induced Chronic Liver Injury

Hepatic fibrogenesis, a complex process that involves a marked accumulation of extracellular matrix components, activation of cells capable of producing matrix materials, cytokine release, and tissue remodeling, is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The MMP-TIMP balance can regulate liver fibrogenesis. The aim of this study was to evaluate the expression patterns of MMPs and TIMPs during thioacetamide (TAA)-induced liver fibrogenesis. Chronic liver injury was induced with TAA (200 mg/kg i.p.) for 4 or 7 weeks in male Sprague-Dawley rats. Hepatic injury and fibrosis were assessed by hematoxylin-eosin (H&E) staining, and collagen deposition was confirmed by Sirius Red staining. The level of hepatic injury was quantified by serological analysis. The transcriptional and translational levels of alpha-smooth muscle actin (alpha-SMA), MMPs, and TIMPs in the liver were measured by Western blotting, RT-PCR, and immunohistochemistry. MMP, TIMP, and alpha-SMA were observed along fibrotic septa and portal spaces around the lobules. TAA treatment increased transcription of both MMPs and TIMPs, but only TIMPs showed increased translation. The dominant expression of TIMPs may regulate the function of MMPs to maintain liver fibrosis induced by TAA.

Análisis del resultado de pruebas hepáticas en pacientes psoriáticos tratados con metotrexato: Estudio retrospectivo / Serum liver tests in patients treated with methotrexate: A retrospective analysis

Background: Methotrexate is one of the best systemic treatments for psoriasis. However it has significant adverse effects such as myelotoxicity and hepatotoxicity. Aim: To evaluate serum liver test in psoríatic patients treated with methotrexate. Material and Methods: Retrospective review of medical records of psoríatic patients treated with methotrexate between the years 2000 and 2005. All patients received a minimum of 7.5 mg weekly of methotrexate, for at íeast 4 weeks. Results: Sixty three patients were included. Mean cumulative dose of methotrexate was 576 mg. Thirty two percent had alterations in liver tests, but only 9 percent had values that duplicated the upper limit of normal range of aminotransferases or alkaline phosphatases or a serum bilirubin over 2 mg/dl. We did not find a direct relationship between the dose of methotrexate and the magnitude of liver test alterations. Only one patient exceeded 1.5 g as cumulative dose. A liver biopsy performed to him, did not show signs of fibrosis. Conclusions: This retrospective study does not show a direct relationship between weekly doses, cumulated dose and length of treatment with methotrexate, and the degree of alteration of serum liver tests.

Amiodarone-induced Hepatitis and Polyneuropathy

Amiodarone chlorhydrate is a diiodated benzofuran derivative, and it is used to treat cardiac rhythm abnormalities. Hepatotoxicity is a relatively uncommon side effect of amiodarone, and symptomatic hepatic dysfunction occurs in fewer than 1% of the patients taking amiodarone. Cirrhosis is a rare complication that's been confirmed in 12 cases. Peripheral neuropathy occurs in 10% of patients taking aminodarone. We report here on an unusual case of amiodarone-induced hepatotoxicity and peripheral neurotoxicity. A 75 year old man with normal liver function was given amiodarone for treating his atrial fibrillation and heart failure. He developed nausea, vomiting, muscle weakness and wasting after 17.8 months therapy with amiodarone (400 mg orally once per day). Liver biopsy showed the presence of foam cells in the hepatic sinusoids and Mallory bodies in the periportal hepatocytes on light microscopy. Sural nerve biopsy showed demyelination, and nerve conduction studies showed mixed sensorimotor polyneuropathy. These observations show the necessity of monitoring the hepatic function and conducting neurologic examination of the patients treated with amiodarone.

Biopsy or biochemistry? the monitoring of hepatic fibrosis from methotrexate

Hepatic fibrosis is an important consequence of inflammatory disorders affecting the liver, and ultimately progresses to cirrhosis. Here we explore methods for the detection and monitoring of hepatic fibrosis, particularly during methotrexate therapy, in which progressive fibrosis can develop over a number of years in a minority of patients. Liver biopsy remains currently the gold standard to assess fibrosis. However, it has several limitations, including manpower issues, cost, risk of patient injury, including mortality and morbidity, observer variability and sampling variation. Several non-invasive diagnostic tests for fibrosis and cirrhosis have therefore been evaluated. The usefulness of a laboratory test for screening for a pathological abnormality such as fibrosis is critically dependent on the prevalence of the pathology in the population under investigation. When the prevalence is expected to be low, screening tests should have a high negative predictive value, so that large numbers of patients can be spared the next diagnostic step, namely liver biopsy. For the moment, clinicians should use the aspartate aminotransferase [AST] / alanine aminotransferase [ALT] ratio and the AST/platelet [APRI] ratio for monitoring the development of hepatic fibrosis

Cell cycle protein profile of the hepatic stellate cells (HSCs) in dimethylnitrosamine-induced rat hepatic fibrosis

Cell cycle regulating proteins are known to have close relation with the proliferation of the mammalian cells. In injured liver, the number of HSCs is increased from proliferation. However, the expression of cell cycle proteins of HSCs during proliferation remains unevaluated. Therefore, cell cycle protein profiles of HSCs were studied in dimethyl-nitrosamine (DMN)-induced rat liver fibrosis model. Sprague-Dawley rats were intraperitoneally injected of DMN and the animals were sacrificed every week up to 4 weeks. HSCs were separated and the number of the cells in S phase was counted to evaluate the cell proliferation by flow cytometry. The expression of cyclin A, cyclin B, cyclin D1, cdk2, cdk4, cdc2, proliferating cell nuclear antigen (PCNA), p21Cip/WAF1, and p27 was examined with immunoblotting analysis. Portion of S-phase cells peaked 7days after DMN injection. At that time, cyclin A, and PCNA showed significant increase in HSCs compared to untreated HSCs (114% and 116%, respectively, P<0.001). p21Cip/WAF1 was decreased significantly in DMN-treated HSCs compared to control cells (88%, P<0.001). The increase of cyclin A, and PCNA and the decrease of p21Cip/WAF1 seem to play important roles in the proliferation of HSCs during the early period of DMN treatment.

Acompanhamento de um modelo de indução de cirrose em ratos mediante vídeolaparoscopia / Accompanying of a cirrhosis induction model in rat through the videolaparoscopy

Os autores apresentam um modelo de vídeolaparoscopia experimental para avaliar a hepatotoxicidade induzida pelo tetracloreto de carbono (CCl4) em ratos. Nódulos sobre a superfície hepática e aumento significativo das provas de função hepatobiliar (alanina aminotransferase, aspartato aminotransferase, fosfatase alcalina e g -glutamiltranspeptidase) foram observados nos ratos tratados com CCl4. Além disso, cirrose hepática foi diagnosticada por estudo histopatológico em todos os ratos submetidos à administração de CC1(4). Desta maneira, a vídeolaparoscopia experimental em ratos parece ser um método diagnóstico excelente que merece mais investigação para explorar as conseqüências fisiológicas da cirurgia laparoscópica.

Development of an animal model of hepatic fibrosis by excretory-secretory antigen of Ascaris suum.

OBJECTIVE: The excretory-secretory (ES) antigens of Ascaris suum are known to cause hepatic damage in animals. The present study was aimed at developing an animal model of hepatic fibrosis with these antigens. METHODS: Three doses of ES antigens of A. suum were injected into 24 golden hamsters on days 0, 10 and 20. Batches of 8 animals each were sacrificed at 3 days, 45 days and 90 days after the third injection, after collection of blood. Three groups of 6 control animals each were injected with normal saline and were sacrificed similarly. Liver biochemistry, leukocyte migration inhibition test on cells separated from spleen, and liver histology were carried out. RESULTS: Serum ALT levels in experimental animals were significantly higher than those in control animals at days 3, 45 and 90 after the last antigen dose; AST levels were elevated 45 and 90 days after the last dose of ES antigen. Leukocyte migration inhibition in experimental animals was 58.2 (8.5)%, 51.6 (11.2)% and 50.5 (12.8)% at days 3, 45 and 90 after the last antigen dose. Marked centrivenular degeneration and necrosis were observed in liver tissue in all the experimental animals sacrificed 72 h after the last antigen dose. Condensation of reticulin around the portal zone with extension into the liver lobule was observed in 4 of 8 and 7 of 8 experimental animals sacrificed 45 and 90 days, respectively, after the last dose. Control animals did not have such lesions. CONCLUSION: An animal model of hepatic fibrosis could be produced by repeated injection of ES antigens of A. suum.