Effects of larazotide acetate, a tight junction regulator, on the liver and intestinal damage in acute liver failure in rats

2021 ◽  
pp. 096032712110588
Author(s):  
Ali Riza Caliskan ◽  
Mehmet Gul ◽  
Ismet Yılmaz ◽  
Baris Otlu ◽  
Nuray Uremis ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Liver Damage ◽  
Light And Electron Microscopy ◽  
Intestinal Damage ◽  
Intestinal Histology ◽  
Oral Gavage ◽  
Significant Difference ◽  
Serum Ammonia

Background and Aim The epithelial cells are the strongest determinants of the physical intestinal barrier. Tight junctions (TJs) hold the epithelial cells together and allow for selective paracellular permeability. Larazotide acetate (LA) is a synthetic octapeptide that reduces TJ permeability by blocking zonulin receptors. In this study, we aimed to investigate the effects of LA, a TJ regulator, on the liver and intestinal histology in the model of acute liver failure (ALF) in rats. Materials and Methods The thioacetamide (TAA) group received intraperitoneal (ip) injections of 300 mg/kg TAA for 3 days. The TAA+LA(dw) (drinking water) group received prophylactic 0.01 mg/mL LA orally for 7 days before the first dose of TAA. The LA(dw) group received 0.01 mg/mL LA orally. The TAA + LA(g) (gavage) group received prophylactic 0.01 mg/mL LA via oral gavage for 7 days before the first dose of TAA. The LA(g) group received 0.01 mg/mL LA via oral gavage. While liver tissue was evaluated only with light microscopy, intestinal samples were examined with light and electron microscopy. Results Serum ammonia, AST, and ALT levels in the TAA group were significantly higher than in control groups (all p < 0.01). Serum ALT levels in the TAA + LA(dw) group were significantly lower than in the TAA group ( p < 0.05). However, serum ammonia and ALT levels did not differ between the TAA and other groups. Serious liver damage in the TAA group was accompanied by marked intestinal damage. There was no significant difference between the TAA and TAA + LA(dw) groups and TAA and TAA + LA(g) groups for liver damage scores. However, intestinal damage scores significantly decreased in the TAA + LA(dw) group compared to the TAA group. In the TAA + LA(dw) group, fusion occurred between the surface epithelial cells of neighboring villi and connecting regions formed as epithelial bridges between the villi. Conclusion Our findings suggest that LA reduced intestinal damage by acting on TJs in the TAA-induced ALF model in rats.

scholarly journals Continuous renal replacement therapy is associated with reduced serum ammonia levels and mortality in acute liver failure

Hepatology ◽  
2017 ◽  
Vol 67 (2) ◽  
pp. 711-720 ◽  
Author(s):  
Filipe S. Cardoso ◽  
Michelle Gottfried ◽  
Shannan Tujios ◽  
Jody C. Olson ◽  
Constantine J. Karvellas ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Serum Ammonia

scholarly journals COVID-19: a fatal case of acute liver failure associated with SARS-CoV-2 infection in pre-existing liver cirrhosis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jana Ihlow ◽  
Alexander Seelhoff ◽  
Victor M. Corman ◽  
Achim D. Gruber ◽  
Simon Dökel ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Liver Damage ◽  
Cathepsin L ◽  
Fatal Case ◽  
Clinical Signs ◽  
Angiotensin Converting Enzyme 2 ◽  
Severe Liver Damage ◽  
Severe Jaundice ◽  
Transmembrane Serine Protease

Abstract Background The detection of severe acute respiratory syndrome coronavirus (SARS-CoV-2) is challenging, particularly in post-mortem human tissues. However, there is increasing evidence for viral SARS-CoV-2 manifestation in non-respiratory tissues. In this context, it is a current matter of debate, whether SARS-CoV-2 shows hepatotropism. Case presentation Here, we report a case of an 88-year-old women with massive SARS-CoV-2 viremia, severe jaundice and clinical signs of an acute hepatitis, who died within a few days from an acute liver failure without showing any clinical signs of pneumonia. Autopsy revealed a severe chronic and acute liver damage with bile duct infestation by SARS-CoV-2 that was accompanied by higher expressions of angiotensin-converting enzyme-2 (ACE2), Cathepsin L and transmembrane serine protease 2 (TMPRSS2). Conclusion Our findings indicate an enhanced biliary susceptibility to viral infection with SARS-CoV-2, that might have resulted from pre-existing severe liver damage. Furthermore, our findings emphasize the differential diagnosis of coronavirus disease 2019 (COVID-19)-associated liver failure in the clinical setting of an inexplicable jaundice.

Persistence of Parvovirus B19 in liver from transplanted patients with acute liver failure

2020 ◽  
Vol 15 (5) ◽  
pp. 307-317 ◽  
Author(s):  
Arthur DR Alves ◽  
Juliana G Melgaço ◽  
Rita de Cássia NC Garcia ◽  
Jessica V Raposo ◽  
Vanessa S de Paula ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Liver Damage ◽  
Parvovirus B19 ◽  
Transcript Expression ◽  
Mrna Transcript ◽  
Serological Tests ◽  
Infected Liver

Aim: In this study, we investigated the presence of B19V in liver tissues from patients with acute liver failure (ALF) and evaluated the viral activity in infected liver. Methods: Serum and liver samples from 30 patients who underwent liver transplantation for ALF were investigated for B19V infection by real-time PCR, serological tests and examination of B19V mRNA (transcript) expression in the liver. Results: The serum and liver samples from seven patients were B19V DNA positive (103–105 copies/ml). Most of them presented detectable anti-B19V IgG, indicating persistent infection. B19V mRNA was detected in all patients, demonstrating intra-hepatic replication. Conclusion: B19V infection of the liver during the course of non-A-E ALF suggested a role of B19V, which produced the worst outcome in co-infected patients and in patients with cryptogenic ALF, in liver damage.

scholarly journals Five-day outcome of hepatitis E-induced acute liver failure in the ICU

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Debashis Chowdhury ◽  
Farhana Mahmood ◽  
Cathryn Edwards ◽  
Simon D. Taylor-Robinson
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Poor Country ◽  
Hepatitis B Surface Antigen ◽  
Hepatitis E ◽  
Additional Risk Factor ◽  
List Type ◽  
Igm Antibody ◽  
Significant Difference ◽  
King’S College Criteria

Abstract Background Hepatitis E virus (HEV) is an important cause of acute liver failure (ALF) in Bangladesh with pregnant mothers being more vulnerable. As HEV occurs in epidemics, it limits medical capabilities in this resource-poor country. Cerebral oedema, resulting in raised intracranial pressure (ICP), is an important cause of morbidity and mortality. Practical treatments are currently few. To study the baseline characteristics and clinical outcome of HEV-induced ALF in a recent HEV epidemic To detect raised ICP clinically and observe response to mannitol infusion. This was a prospective cohort study from June until August 2018 of 20 patients admitted to the intensive care unit (ICU) of a major Bangladeshi Referral Hospital with HEV-induced ALF. We diagnosed HEV infection by detecting serum anti-HEV IgM antibody. All were negative for hepatitis B surface antigen and hepatitis A IgM antibody. Data were collected on 5-day outcome after admission to ICU, monitoring all patients for signs of raised ICP. An intravenous bolus of 20% mannitol was administered at a single time point to patients with raised ICP. Results Twenty patients were included in the study. Ten (50%) patients, seven (70%) females, received mannitol infusion. HE worsened in eight (40%): seven female and three pregnant. Glasgow Coma scores deteriorated in six (30%): all (100%) females and three pregnant. Consciousness status was not significantly different between pregnant and non-pregnant subjects, nor between those who received mannitol and those who did not. Six patients met King’s College Criteria for liver transplantation. Conclusions Female patients had a worse outcome, but pregnancy status was not an additional risk factor in our cohort. Mannitol infusion was also not associated with a significant difference in outcome.

Oral administration of Simbioflora® (synbiotic) attenuates intestinal damage in a mouse model of 5-fluorouracil-induced mucositis

2018 ◽  
Vol 9 (3) ◽  
pp. 477-486 ◽  
Author(s):  
L.M. Trindade ◽  
V.D. Martins ◽  
N.M. Rodrigues ◽  
E.L.S. Souza ◽  
F.S. Martins ◽  
...  
Keyword(s):  
Weight Loss ◽  
Oral Administration ◽  
Intestinal Permeability ◽  
Lactobacillus Rhamnosus ◽  
Mucosal Damage ◽  
Mucosal Inflammation ◽  
Intestinal Damage ◽  
Intestinal Histology ◽  
Oral Gavage ◽  
Bifidobacterium Lactis

The use of probiotics to prevent or treat mucosal inflammation has been studied; however, the combined effect of probiotics and prebiotics is unclear. The aim of this study was to test whether oral administration of a synbiotic (Simbioflora®) preparation containing Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus acidophilus and Bifidobacterium lactis plus fructooligosaccharide could help control mucosal inflammation in experimental mucositis induced by 5-fluorouracil (5-FU). Male BALB/c mice were randomly divided into six groups: control (CTL), control + prebiotic (CTL+P), control + synbiotic (CTL+S), mucositis (MUC), mucositis + prebiotic (MUC+P), and mucositis + synbiotic (MUC+S). Mice from the CTL+S, MUC+S, CTL+P, and MUC+P groups received synbiotic or prebiotic daily by oral gavage for 13 days. Mice in the CTL and MUC groups received the same volume of saline. On day 11, mice in the MUC, MUC+P, and MUC+S groups received an intraperitoneal injection of 300 mg/kg 5-FU to induce mucositis. After 72 h, all mice were euthanised. Intestinal permeability, intestinal histology, and biochemical parameters were analysed. Group MUC showed a greater weight loss and increased intestinal permeability (0.020 counts per min [cpm]/g) compared to the CTL group (0.01 cpm/g) P<0.05. Both treatments attenuated weight loss compared to the MUC group. Nonetheless, the synbiotic caused a greater reduction in intestinal permeability (0.012 cpm/g) compared to the MUC (0.020 cpm/g) and MUC+P (0.016 cpm/g) groups P<0.05. Mice in groups MUC+P and MUC+S displayed significant recovery of lesions and maintenance of the mucus layer. There were no differences in the short-chain fatty acid concentrations in the faeces between the MUC and CTL groups (P>0.05). Increased acetate and propionate concentrations were evidenced in the faeces of the MUC+P and MUC+S groups. Only the synbiotic treatment increased the butyrate concentration (P<0.05). The results indicate that administration of synbiotic can decrease mucosal damage caused by mucositis.

scholarly journals Influence of matrix nature on the functional efficacy of biomedical cell product for the regeneration of damaged liver (experimental model of acute liver failure)

2017 ◽  
Vol 19 (2) ◽  
pp. 78-89
Author(s):  
S. V. Gautier ◽  
M. Yu. Shagidulin ◽  
N. A. Onishchenko ◽  
I. M. Iljinsky ◽  
V. I. Sevastianov
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Experimental Model ◽  
Cell Activity ◽  
Liver Cells ◽  
Control Group ◽  
Nanostructured Composite ◽  
Hydrogel Matrix ◽  
Significant Difference ◽  
Long Time

Aim. A comparative analysis of the functional efficacy of biomedical cell products (BMCP) for the regeneration of damaged liver based on biopolymer scaffolded porous and hydrogel matrices was performed on the experimental model of acute liver failure. Materials and methods. Matrices allowed for clinical use were employed for BMCP in the form of a sponge made from biopolymer nanostructured composite material (BNCM) based on a highly purified bacterial copolymers of poly (β-hydroxybutyrate-co-β-oxyvalerate) and polyethylene glycol and a hydrogel matrix from biopolymer microheterogeneous collagen-containing hydrogel (BMCH). Cellular component of BMCP was represented by liver cells and multipotent mesenchymal bone marrow stem cells. The functional efficacy of BMCP for the regeneration of damaged liver was evaluated on the experimental model of acute liver failure in Wistar rats (n = 40) via biochemical, morphological, and immunohistochemical methods. Results. When BMCP was implanted to regenerate the damaged liver on the basis of the scaffolded BNCM or hydrogel BMCH matrices, the lethality in rats with acute liver failure was absent; while in control it was 66.6%. Restoration of the activity of cytolytic enzyme levels and protein-synthetic liver function began on day 9 after modeling acute liver failure, in contrast to the control group, where recovery occurred only by days 18–21. Both matrices maintained the viability and functional activity of liver cells up to 90 days with the formation of blood vessels in BMCP. The obtained data confirm that scaffolded BNCM matrix and hydrogel BMCH matrix retain for a long time (up to 90 days) the vital activity of the adherent cells in the BMCP composition, which allows using them to correct acute liver failure. At the same time, hydrogel matrix due to the presence of bioactive components contributes to the creation of the best conditions for adhesion and cell activity which accelerate the regeneration processes in the damaged liver compared to BMCP on scaffolded matrix. Conclusion. A statistically significant difference was found between the functional efficacy of the BMCP studied based on BNCM and BMCH matrices. BMCP based on hydrogel BMCH matrix was more effective for the regeneration of damaged liver.

scholarly journals Th1/Th2 Cells and Associated Cytokines in Acute Hepatitis E and Related Acute Liver Failure

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Jian Wu ◽  
Yurong Guo ◽  
Xuan Lu ◽  
Fen Huang ◽  
Feifei Lv ◽  
...  
Keyword(s):  
Viral Load ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Acute Hepatitis ◽  
Hepatitis E ◽  
Th2 Cells ◽  
Upward Trend ◽  
Significant Difference ◽  
Acute Hepatitis E ◽  
Ifn Γ

Background and Aims. The involvement of cellular immunity in the development of hepatitis E virus (HEV) infection is rare. We aimed to study the roles of viral load and Th cell responses in acute hepatitis E (AHE) and HEV-related acute liver failure (HEV-ALF). Methods. We evaluated viral load and Th1/Th2 cytokine levels in 34 patients with HEV infection, including 17 each with AHE or HEV-ALF. Seventeen healthy controls (HCs) were also included who were negative for anti-HEV IgM and IgG. Results. There was no significant difference in viral load and HEV RNA in the AHE and HEV-ALF groups (both P > 0.05 ). The Th lymphocyte levels (CD3+, CD4+) in the AHE and HEV-ALF groups were significantly higher than those in the HC group (both P < 0.05 ), but there was no significant difference between the AHE and HEV-ALF groups ( P > 0.05 ). Both IFN-γ and IL-10 showed gradual upward trend from the HC group to the AHE (both P < 0.01 ), but IFN-γ showed a sharp downward trend from the AHE group to the HEV-ALF group ( P < 0.01 ) and IL-4 showed gradual upward trend from the AHE group to the HEV-ALF group ( P < 0.01 ).There was no significant difference in Th1 and Th2 cytokines between the HEV RNA(+) group and HEV RNA(-) group (all P > 0.05 ). Th2 bias was observed from the AHE ( ratio = 58.65 ) to HEV-ALF ( ratio = 1.20 ) groups. The level of IFN-γ was associated with the outcome of HEV-ALF patients. Conclusions. HEV viral load was not associated with aggravation of AHE, and the HEV-ALF patients showed significant Th2 bias, which may be involved in the aggravation of AHE.

scholarly journals Sa1014 The Clinical Features and Prognosis of Acute Liver Failure Due to Ischemic Liver Damage

2014 ◽  
Vol 146 (5) ◽  
pp. S-937
Author(s):  
Yasuhiro Tsuda ◽  
Keisuke Yokohama ◽  
Hideko Ohama ◽  
Tetsuya Sujishi ◽  
Yusuke Tsuchimoto ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Clinical Features ◽  
Liver Damage
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