Skeletal muscle myopenia in mice model of bile duct ligation and carbon tetrachloride-induced liver cirrhosis

Skeletal muscle myopathy is universal in cirrhotic patients, however, little is known about the main mechanisms involved. The study aims to investigate skeletal muscle morphological, histological, and functional modifications in experimental models of cirrhosis and the principal molecular pathways responsible for skeletal muscle myopathy. Cirrhosis was induced by bile duct ligation (BDL) and carbon tetrachloride (CCl4) administration in mice. Control animals (CTR) underwent bile duct exposure or vehicle administration only. At sacrifice, peripheral muscles were dissected and weighed. Contractile properties of extensor digitorum longus (EDL) were studied in vitro. Muscle samples were used for histological and molecular analysis. Quadriceps muscle histology revealed a significant reduction in cross-sectional area of muscle and muscle fibers in cirrhotic mice with respect to CTR. Kinetic properties of EDL in both BDL and CCl4 were reduced with respect to CTR; BDL mice also showed a reduction in muscle force and a decrease in the resistance to fatigue. Increase in myostatin expression associated with a decrease in AKT-mTOR expressions was observed in BDL mice, together with an increase in LC3 protein levels. Upregulation of the proinflammatory citochines TNF-a and IL6 and an increased expression of NF-kB and MuRF-1 were observed in CCl4 mice. In conclusion, skeletal muscle myopenia was present in experimental models of BDL and CCl4-induced cirrhosis. Moreover, reduction in protein synthesis and activation of protein degradation were the main mechanisms responsible for myopenia in BDL mice, while activation of ubiquitin-pathway through inflammatory cytokines seems to be the main potential mechanism involved in CCl4 mice

The bile duct ligated rat : a relevant model to study muscle mass loss in cirrhosis

Muscle mass loss and hepatic encephalopathy (complex neuropsychiatric disorder) are serious complications of chronic liver disease (cirrhosis) which impact negatively on clinical outcome and quality of life and increase mortality. Liver disease leads to hyperammonemia and ammonia toxicity is believed to play a major role in the pathogenesis of hepatic encephalopathy. However, the effects of ammonia are not brain-specific and therefore may also affect other organs and tissues including muscle. The precise pathophysiological mechanisms underlying muscle wasting in chronic liver disease remains to be elucidated. In the present study, we characterized body composition as well as muscle protein synthesis in cirrhotic rats with hepatic encephalopathy using the 6-week bile duct ligation (BDL) model which recapitulates the main features of cirrhosis. Compared to sham-operated control animals, BDL rats display significant decreased gain in body weight, altered body composition, decreased gastrocnemius muscle mass and circumference as well as altered muscle morphology. Muscle protein synthesis was also significantly reduced in BDL rats compared to control animals. These findings demonstrate that the 6-week BDL experimental rat is a relevant model to study liver disease-induced muscle mass loss

Holographic principle in the BDL brane cosmology

We study the holographic principle in the brane cosmology. Especially we describe how to accommodate the 5D anti de Sitter Schwarzschild (AdSS$_5$) black hole in the Binetruy-Deffayet-Langlois (BDL) approach of brane cosmology. It is easy to make a connection between a mass $M$ of the AdSS$_5$ black hole and a conformal field theory (CFT)-radiation dominated universe on the brane in the moving domain wall approach. But this is not established in the BDL approach. In this case we use two parameters $C_1, C_2$ in the Friedmann equation. These arise from integration and are really related to the choice of initial bulk matter. If one chooses a bulk energy density $\rho_B$ to account for a mass $M$ of the AdSS$_5$ black hole and the static fifth dimension, a CFT-radiation term with $\rho_{CFT} \sim M/a^{4}$ comes out from the bulk matter without introducing a localized matter distribution on the brane. This means that the holographic principle can be established in the BDL brane cosmology.Comment: 9 pages, a version to appear in PR

Effect of Obstructive Jaundice and Nitric Oxide on the Profiles of Intestinal Bacterial Flora in Wild and iNOS−/− Mice

We previously reported that the plasma level of endotoxin and colonic expression of IgA in the mouse increased with obstructive jaundice induced by bile duct ligation (BDL). To elucidate the mechanism of the BDL-induced increase, we analyzed the effect of BDL on intestinal flora in wild type and inducible nitric oxide synthase (iNOS)-deficient mice (iNOS−/−) using the terminal restriction fragment length polymorphism analysis (T-RFLP) and 16S rDNA clone libraries. The amounts of bacterial DNA detected in fecal samples from both animal groups pretreated with antibiotics were extremely low as compared with untreated groups. We found that the profiles of enteric bacteria changed markedly after BDL. The bacterial composition is significantly different between not only wild type and iNOS−/− mice but also those before and after BDL, respectively. Among enteric bacteria examined, Lactobacillus murinus was found to increase markedly after BDL in rectum of both animal groups. However, Escherichia coli markedly increased after BDL in the iNOS−/− mice. These findings suggest that profiles of enteric flora change markedly in animals during obstructive jaundice by some mechanism that is affected by bile constituents and iNOS-derived NO

The protective effects of ursodeoxycholic acid and the selective cyclooxygenase-2 inhibitor celecoxib on liver damage in an experimental cholestasis model

Aim: Cholestasis leads to liver cell death, fibrosis, cirrhosis, and eventually liver failure. Ursodeoxycholic acid (UDCA) is the only Food and Drug Administration-approved treatment for cholestatic disorders. Hepatic cyclooxygenase-2 (COX-2) expression increases in various chronic liver diseases caused either by viruses or toxins. The present study was conducted to investigate the effects of UDCA and the selective COX-2 inhibitor celecoxib on inflammation and fibrogenesis in a rat model of cholestasis induced by bile duct ligation (BDL). Methods: Fifty Sprague–Dawley rats that underwent common BDL for 21 days were assigned to one of five treatment groups (sham-operation, BDL, daily UDCA treatment following BDL, daily celecoxib treatment following BDL, and daily celecoxib and UDCA combination treatment following BDL). Serum and liver samples were collected after 21 days. Fibrosis, ductular proliferation, and portal inflammation were scored in liver samples. Liver function tests were evaluated. Results: In comparison with the control group, the BDL group showed hepatic damage as evidenced by elevation in serum biochemical and histological changes such as ductular reaction, fibrosis, and inflammation. These pathophysiological changes were attenuated by chronic UDCA and selective COX-2 inhibitor celecoxib supplementation. Conlusion: Our findings indicate that the addition of Celecoxib to UDCA reduces liver inflammation and fibrosis and might be an effective supplemental therapy with UDCA for cholestatic diseases. The beneficial effects of chronic UDCA and Celecoxib supplementation may be associated with their potential cytoprotective, anti-oxidative and anti-inflammatory effects

Protective Effect of Curcumin on Liver Damage Induced by Biliary Obstruction in Rats

Objective: The aim of this study is to evaluate the possible protective effects of curcumin against cholestatic oxidative stress and liver damage in common bile duct ligated rats. Material and Methods: A total of 18 male Wistar albino rats were divided into three groups: control, common bile duct ligation (BDL) and BDL+curcumin. Each group contained 6 animals. The rats in the curcumin treated group were given curcumin (100 mg/kg) once a day orally for 14 days, starting 3 days prior to BDL operation. Following 14 days of treatment, all the animals were decapitated and liver tissue samples were obtained for histopathological investigation. Results: The changes demonstrating the bile duct proliferation and fibrosis in expanded portal tracts, including the extension of proliferated bile ducts into lobules, mononuclear cells, and neutrophil infiltration into the widened portal areas, were observed in BDL group. Treatment of BDL with curcumin attenuated liver damage. Both the elevated alpha smooth muscle actin (alpha-SMA), and the activity of TUNEL in the BDL were observed to be reduced with the curcumin treatment. Conclusion: Our data indicate that curcumin reduced BDL-induced cholestatic liver injury, bile duct proliferation, fibrosis

Changes in glass consumption in Pergamon (Turkey) from Hellenistic to late Byzantine and Islamic times

We present compositional data for nearly 100 glass samples from Pergamon, western Turkey, spanning 1500 years from the Hellenistic to Late Byzantine and Islamic periods. The data shows the use of already-known Roman glass groups during the first half of the time frame, for imported vessels as well as locally worked glass. No compositional change is seen related to the introduction of glass blowing for either of the glass groups in use during this time. During the first half of the 1st millennium AD, two previously little-known boron- and alumina-rich compositional groups emerge. These glass groups, thought to be regionally produced, dominate glass compositions in Pergamon during the mid-to late Byzantine and Islamic periods, indicating a major shift in glass supply and a fragmentation of the economy into more regional units. Plant-ash glass, from the 9th century AD replacing mineral natron glass in the Levant, plays only a minor role in Byzantine and Islamic Pergamon