scholarly journals Sarcopenia Induced by Chronic Liver Disease in Mice Requires the Expression of the Bile Acids Membrane Receptor TGR5

2020 ◽  
Vol 21 (21) ◽  
pp. 7922
Author(s):  
Johanna Abrigo ◽  
Fabián Campos ◽  
Francisco Gonzalez ◽  
Francisco Aguirre ◽  
Andrea Gonzalez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Bile Acids ◽  
Fiber Type ◽  
Ring Finger ◽  
Chronic Liver ◽  
Receptor Expression ◽  
Skeletal Muscle Atrophy ◽  
And Oxidative Stress

Sarcopenia is a condition of muscle dysfunction, commonly associated with chronic liver disease (CLD), characterized by a decline in muscle strength, the activation of the ubiquitin-proteasome system (UPS), and oxidative stress. We recently described a murine model of CLD-induced sarcopenia by intake of hepatotoxin 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), which presents an increase in plasma bile acids (BA). BA induced skeletal muscle atrophy through a mechanism dependent on the Takeda G protein-coupled receptor 5 (TGR5) receptor. In the present study, we evaluated the role of TGR5 signaling in the development of sarcopenia using a model of DDC-induced CLD in C57BL6 wild-type (WT) mice and mice deficient in TGR5 expression (TGR5−/− mice). The results indicate that the decline in muscle function and contractibility induced by the DDC diet is dependent on TGR5 expression. TGR5 dependence was also observed for the decrease in fiber diameter and sarcomeric proteins, as well as for the fast-to-slow shift in muscle fiber type. UPS overactivation, indicated by increased atrogin-1/MAFbx (atrogin-1) and muscle RING-finger protein-1 (MuRF-1) protein levels and oxidative stress, was abolished in tibialis anterior muscles from TGR5−/− mice. Our results collectively suggest that all sarcopenia features induced by the DDC-supplemented diet in mice are dependent on TGR5 receptor expression.

scholarly journals A Nutraceutical Rich in Docosahexaenoic Acid Improves Portal Hypertension in a Preclinical Model of Advanced Chronic Liver Disease

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2358 ◽  
Author(s):  
Boyer-Diaz ◽  
Domingo ◽  
de Gregorio ◽  
Manicardi ◽  
Aristu-Zabalza ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Portal Hypertension ◽  
Liver Disease ◽  
Docosahexaenoic Acid ◽  
Chronic Liver Disease ◽  
Stellate Cell ◽  
Preclinical Study ◽  
Chronic Liver ◽  
Preclinical Model ◽  
And Oxidative Stress

Inflammation and oxidative stress play a key role in the pathophysiology of advanced chronic liver disease (ACLD) and portal hypertension (PH). Considering the current lack of effective treatments, we evaluated an anti-inflammatory and antioxidant nutraceutical rich in docosahexaenoic acid (DHA) as a possible therapy for ACLD. We investigated the effects of two-week DHA supplementation (500 mg/kg) on hepatic fatty acids, PH, oxidative stress, inflammation, and hepatic stellate cell (HSC) phenotype in rats with ACLD. Additionally, the effects of DHA were evaluated in murine macrophages and human HSC. In contrast to vehicle-treated animals, cirrhotic rats receiving DHA reestablished a healthy hepatic fatty acid profile, which was associated with an improvement in PH. The mechanisms underlying this hemodynamic improvement included a reduction in oxidative stress and inflammation, as well as a marked HSC deactivation, confirmed in human HSC. Experiments with cultured macrophages showed that treatment with DHA protects against pro-inflammatory insults. The present preclinical study demonstrates that a nutraceutical rich in DHA significantly improves PH in chronic liver disease mainly by suppressing inflammation and oxidative stress-driven HSC activation, encouraging its evaluation as a new treatment for PH and cirrhosis.

Elemental Zinc Is Inversely Associated with C-Reactive Protein and Oxidative Stress in Chronic Liver Disease

2017 ◽  
Vol 178 (2) ◽  
pp. 189-193 ◽  
Author(s):  
Md. Giash Uddin ◽  
Mohammad Salim Hossain ◽  
Md. Atiqur Rahman ◽  
A. H. M. Mazbah Uddin ◽  
Md. Shafiullah Bhuiyan
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
And Oxidative Stress

scholarly journals Protective Effect of Angiotensin 1–7 on Sarcopenia Induced by Chronic Liver Disease in Mice

2020 ◽  
Vol 21 (11) ◽  
pp. 3891 ◽  
Author(s):  
Francisco Aguirre ◽  
Johanna Abrigo ◽  
Francisco Gonzalez ◽  
Andrea Gonzalez ◽  
Felipe Simon ◽  
...  
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Fiber Diameter ◽  
Morphological Changes ◽  
Fiber Type ◽  
Renin Angiotensin System ◽  
Ubiquitin Proteasome System ◽  
Protective Role ◽  
Chronic Liver ◽  
Fiber Types

Sarcopenia associated with chronic liver disease (CLD) is one of the more common extrahepatic features in patients with these pathologies. Among the cellular alterations observed in the muscle tissue under CLD is the decline in the muscle strength and function, as well as the increased fatigue. Morphological changes, such as a decrease in the fiber diameter and transition in the fiber type, are also reported. At the molecular level, sarcopenia for CLD is characterized by: (i) a decrease in the sarcomeric protein, such as myosin heavy chain (MHC); (ii) an increase in the ubiquitin–proteasome system markers, such as atrogin-1/MAFbx1 and MuRF-1/TRIM63; (iii) an increase in autophagy markers, such as LC3II/LC3I ratio. Among the regulators of muscle mass is the renin-angiotensin system (RAS). The non-classical axis of RAS includes the Angiotensin 1–7 [Ang-(1-7)] peptide and its receptor Mas, which in skeletal muscle has anti-atrophic effect in models of muscle wasting induced by immobilization, lipopolysaccharide, myostatin or angiotensin II. In this paper, we evaluated the effect of Ang-(1-7) on the sarcopenia by CLD in a murine model induced by the 5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) hepatotoxin administered through diet. Our results show that Ang-(1-7) administration prevented the decline of the function and strength of muscle and increased the fatigue detected in the DDC-fed mice. Besides, we observed that the decreased fiber diameter and MHC levels, as well as the transition of fiber types, were all abolished by Ang-(1-7) in mice fed with DDC. Finally, Ang-(1-7) can decrease the atrogin-1 and MuRF-1 expression as well as the autophagy marker in mice treated with DDC. Together, our data support the protective role of Ang-(1-7) on the sarcopenia by CLD in mice.

A Silybinphospholipid Complex Prevents Mitochondrial Oxidative Stress in Models of Chronic Liver Disease

2010 ◽  
Vol 49 ◽  
pp. S177
Author(s):  
Francesco Bellanti ◽  
Alessandro Arduini ◽  
Rosanna Tamborra ◽  
Tiziana Rollo ◽  
Maria Blonda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
Mitochondrial Oxidative Stress

Expression of the type 3 inositol 1, 4, 5-trisphosphate receptor according to the chronic liver disease etiology in hepatocellular carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16604-e16604
Author(s):  
Paulo Henrique Costa Diniz ◽  
Marcone Loiola dos Santos ◽  
Andressa França ◽  
Antônio Carlos Melo Lima Filho ◽  
Paula Vieira Teixeira Vidigal ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Mitotic Index ◽  
Chronic Liver ◽  
Receptor Expression ◽  
Cryptogenic Cirrhosis ◽  
Inositol 1 ◽  
Trisphosphate Receptor ◽  
Type 3

e16604 Background: The expression of type 3 isoform of the inositol 1, 4, 5-trisphosphate receptor (ITPR-3), an intracellular calcium (Ca2+) channel reported in liver cancer cells, is important in the Ca2+ signalling. Thus, it may be involved in the many events of hepatocarcinogenesis. Here, we investigated the ITPR-3 expression in hepatocellular carcinoma (HCC) and its association with clinicopathological parameters and long-term outcomes, according to the etiology of underlying chronic liver disease (CLD). Methods: Clinical and laboratory data from patients (n = 53) who underwent orthotopic liver transplantation for HCC treatment in a Brazilian referral center were retrospectively collected. After pathological reviewing of their explanted liver samples, ITPR-3 expression in both tumor and underlying cirrhosis were assessed by immunohistochemistry, and quantified using density histograms in the ImageJ software. Event (tumor recurrence or death from any cause) occurrence and event-free survival (EFS) were analysed. Results: Hepatitis C virus (HCV) (n = 31), alcohol abuse (n = 16) and cryptogenic cirrhosis (n = 6) were the underlying CLD etiology, and the groups were, in general, well balanced regarding clinicopathological indices. Median EFS was 78.9 months (range, 63.6-94.1). The ITPR-3 expression profile was cytoplasmatic, predominantly perinuclear, and was stronger in tumor than in adjacent cirrhosis, considering all etiologies together (intensity 9.1% higher in tumors, p < 0.001) However, analyzing each etiologic group, the cryptogenic was the only one in which there was no difference between tumor and underlying CLD. Comparing the ITPR-3 expression only in tumors, there was no difference regarding the etiology of CLD. The tumor ITPR-3 higher intensity was correlated with higher serum aspartate alanine-transferases (ALT) levels (p = 0.018) and lower mitotic index ( < 5 per 10 high power fields) (p = 0.009). There was no association between receptor expression and event occurrence or EFS. Conclusions: The ITPR-3 was expressed in HCC, regardless of the underlying CLD etiology. Its correlation with mitotic index, a cell proliferation marker, was demonstrated, but there were no associations with clinical outcomes. Apart from cryptogenic cirrhosis, ITPR-3 expression was more intense in tumors than in underlying cirrhosis. These findings suggest that ITPR-3 could have a role in carcinogenesis. However, the prognostic and therapeutic implications need to be investigated.

scholarly journals Oxidative Stress in Chronic Liver Disease and Portal Hypertension: Potential of DHA as Nutraceutical

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2627 ◽  
Author(s):  
Zoe Boyer-Diaz ◽  
Paloma Morata ◽  
Peio Aristu-Zabalza ◽  
Albert Gibert-Ramos ◽  
Jaime Bosch ◽  
...  
Keyword(s):  
Public Health ◽  
Oxidative Stress ◽  
Portal Hypertension ◽  
Liver Disease ◽  
Docosahexaenoic Acid ◽  
Chronic Liver Disease ◽  
Current Knowledge ◽  
Chronic Liver ◽  
Public Health Issue ◽  
Clinical Scenarios

Chronic liver disease constitutes a growing public health issue worldwide, with no safe and effective enough treatment clinical scenarios. The present review provides an overview of the current knowledge regarding advanced chronic liver disease (ACLD), focusing on the major contributors of its pathophysiology: inflammation, oxidative stress, fibrosis and portal hypertension. We present the benefits of supplementation with docosahexaenoic acid triglycerides (TG-DHA) in other health areas as demonstrated experimentally, and explore its potential as a novel nutraceutical approach for the treatment of ACLD and portal hypertension based on published pre-clinical data.

scholarly journals Determinants of Serum Bile Acids in Chronic Liver Disease

1981 ◽  
Vol 81 (5) ◽  
pp. 959-964 ◽  
Author(s):  
Pierre Paré ◽  
John C. Hoefs ◽  
Mary Ashcavai
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Bile Acids ◽  
Chronic Liver ◽  
Serum Bile Acids
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