Intestinal mucosal proliferation, apoptosis and oxidative stress in patients with liver cirrhosis

Assimakopoulos, Stelios F.; Tsamandas, Athanassios C.; Tsiaoussis, Georgios I.; Karatza, Elli; Zisimopoulos, Dimitrios; Maroulis, Ioannis; Kontogeorgou, E.; Georgiou, Christos D.; Scopa, Chrisoula D.; Thomopoulos, K.

doi:10.1016/s1665-2681(19)31369-9

Cited by 30 publications

(28 citation statements)

References 29 publications

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“…Altered immunity in cirrhosis is reflected by an increased production of proinflammatory cytokines and cell activation markers, which are more pronounced than noncirrhotic portal hypertension (NCPH) . Systemic oxidative stress is also increased in liver cirrhosis …”

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confidence: 99%

“…(7) Systemic oxidative stress is also increased in liver cirrhosis. (8,9) Because cirrhosis is a state of chronically altered metabolic, inflammatory, and circulatory milieu, it is likely to lead to exhaustion of the bone marrow (BM) stem cell compartment due to "inflamm-ageing" of the hematopoietic stem cell (HSC) compartment and the niche cells. (10) The BM dysfunction, in turn, could contribute to decreased peripheral blood cell counts and perturbations in the immune system.…”

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confidence: 99%

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Bone marrow stem cells and their niche components are adversely affected in advanced cirrhosis of the liver

et al. 2016

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confidence: 99%

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confidence: 99%

Bone marrow stem cells and their niche components are adversely affected in advanced cirrhosis of the liver

et al. 2016

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“…In these models, intestinal endotoxin levels increased in the portal vein . An imbalance between proliferation and apoptosis, in addition to intestinal mucosal atrophy and edema, which is associated with portal hypertension or the absence of bile acids, results in increased production of inflammatory cytokines and enhanced oxidative stress in the liver . Accordingly, we carried out immunohistochemistry for the intestinal TJP ZO‐1.…”

Section: Discussionmentioning

confidence: 99%

“…[36][37][38] An imbalance between proliferation and apoptosis, in addition to intestinal mucosal atrophy and edema, which is associated with portal hypertension or the absence of bile acids, results in increased production of inflammatory cytokines and enhanced oxidative stress in the liver. 27,39,40 Accordingly, we carried out immunohistochemistry for the intestinal TJP ZO-1. The expression of intestinal ZO-1 was reduced in the CDAA model compared to that in the CSAA group; however, it was increased with MIYAIRI 588 treatment.…”

Section: Discussionmentioning

confidence: 99%

Combining probiotics and an angiotensin‐II type 1 receptor blocker has beneficial effects on hepatic fibrogenesis in a rat model of non‐alcoholic steatohepatitis

Sawada

Kawaratani

Kubo

et al. 2018

Hepatology Research

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Aim Intestinal endotoxin is important for the progression of non‐alcoholic steatohepatitis (NASH). Circulating endotoxin levels are elevated in most animal models of diet‐induced non‐alcoholic fatty liver disease (NAFLD) and NASH. Furthermore, plasma endotoxin levels are significantly higher in NAFLD patients, which is associated with small intestinal bacterial overgrowth and increased intestinal permeability. By improving the gut microbiota environment and restoring gut‐barrier functions, probiotics are effective for NASH treatment in animal models. It is also widely known that hepatic fibrosis and suppression of activated hepatic stellate cells (Ac‐HSCs) can be attenuated using an angiotensin‐II type 1 receptor blocker (ARB). We thus evaluated the effect of combination probiotics and ARB treatment on liver fibrosis using a rat model of NASH. Methods Fisher 344 rats were fed a choline‐deficient/L‐amino acid‐defined (CDAA) diet for 8 weeks to generate the NASH model. Animals were divided into ARB, probiotics, and ARB plus probiotics groups. Therapeutic efficacy was assessed by evaluating liver fibrosis, the lipopolysaccharide Toll‐like receptor (TLR)4 regulatory cascade, and intestinal barrier function. Results Both probiotics and ARB inhibited liver fibrosis, with concomitant HSC activation and suppression of liver‐specific transforming growth factor‐β and TLR4 expression. Probiotics reduced intestinal permeability by rescuing zonula occludens‐1 disruption induced by the CDAA diet. Angiotensin‐II type 1 receptor blocker was found to directly suppress Ac‐HSCs. Conclusions Probiotics and ARB are effective in suppressing liver fibrosis through different mechanisms. Currently both drugs are in clinical use; therefore, the combination of probiotics and ARB is a promising new therapy for NASH.

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“…Similarly, malignant biliary obstruction patients had higher levels of intestinal oxidative stress [124] and cirrhotic patients had increased intestinal lipid peroxidation [125]. …”

Section: Possible Role Of Increased Circulatory Adma In the Multiple mentioning

confidence: 99%

Increased Circulatory Asymmetric Dimethylarginine and Multiple Organ Failure: Bile Duct Ligation in Rat as a Model

Sheen

Chen

Tain

et al. 2014

IJMS

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Bile duct ligation (BDL)-treated rats exhibit cholestasis, increased systemic oxidative stress, and liver fibrosis, which ultimately lead to liver cirrhosis. Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of nitric oxide synthase that can decrease the synthesis of nitric oxide. BDL rats have higher plasma and hepatic ADMA levels, which may be due to increased hepatic protein arginine methyltransferase-1 and decreased dimethylarginine dimethylaminohydrolase expression. BDL rats also exhibit renal and brain damage characterized by increased tissue ADMA concentrations. The increased plasma ADMA levels and multiple organ damages seen here are also observed following multiple organ failures associated with critical illness. This review discusses the dysregulation of ADMA in major organs in BDL rats and the role of increased ADMA in multiple organ damages.

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Intestinal mucosal proliferation, apoptosis and oxidative stress in patients with liver cirrhosis

Cited by 30 publications

References 29 publications

Bone marrow stem cells and their niche components are adversely affected in advanced cirrhosis of the liver

Bone marrow stem cells and their niche components are adversely affected in advanced cirrhosis of the liver

Combining probiotics and an angiotensin‐II type 1 receptor blocker has beneficial effects on hepatic fibrogenesis in a rat model of non‐alcoholic steatohepatitis

Increased Circulatory Asymmetric Dimethylarginine and Multiple Organ Failure: Bile Duct Ligation in Rat as a Model

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