scholarly journals Jie-Du-Hua-Yu Granules Promote Liver Regeneration in Rat Models of Acute Liver Failure: miRNA-mRNA Expression Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Tingshuai Wang ◽  
Na Wang ◽  
Rongzhen Zhang ◽  
Shaodong Huang ◽  
Hua Qiu ◽  
...  
Keyword(s):  
Dna Replication ◽  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Liver Regeneration ◽  
Signaling Pathways ◽  
Metabolic Ratio ◽  
Therapeutic Effects ◽  
Biological Processes ◽  
Rat Models

Purpose. Jie-Du-Hua-Yu (JDHY) granules are a traditional Chinese medicine with known therapeutic effects for the treatment of acute liver failure (ALF). This study explored the potential molecular mechanism(s) of JDHY granules in promoting liver regeneration and preventing ALF. Methods. Rat models of ALF were constructed through administration of D-galactosamine (D-GalN) (600 mg/kg) and lipopolysaccharides (LPS) (20 μg/kg). Rats were gavaged with JDHY granules, and serum and liver samples were collected at 12 h post-D-GalN/LPS administration. The degree of liver injury was evaluated through hepatic pathology and alanine/aspartate aminotransferase (ALT/AST) activity. miRNA chips were used to detect the miRNA expression profiles of rat models. Bioinformatics analysis was used to identify the biological processes and cell signaling pathways mediating the therapeutic effects of JDHY. Real-time PCR (RT-PCR) and western blotting were used to validate the data. Results. JDHY granules could effectively decrease the levels of ALT and AST, relieve D-GalN/LPS-induced liver injury, and improve hepatic function. JDHY granules were found to regulate the expression of 20 miRNAs and 19 mRNAs, which influenced 21 biological processes and 9 signaling pathways. Upon analysis of the therapeutic mechanism(s) governing the effects of JDHY granules on liver regeneration, enhanced DNA replication and an improved cholesterol metabolic ratio were identified. JDHY granules were also found to increase the expression of MCM3, CDK4, and TC, confirming the involvement of these pathways. Moreover, JDHY granules were found to promote hepatocyte mitosis and inhibit the progression of ALF. Conclusion. JDHY granules protect against D-GalN/LPS-induced ALF in rats by promoting liver regeneration through enhanced DNA replication and an improved cholesterol metabolic ratio.

Epiregulin promotes the emergence and proliferation of adult liver progenitor cells

2014 ◽  
Vol 307 (1) ◽  
pp. G50-G57 ◽  
Author(s):  
Kyoko Tomita ◽  
Hiroaki Haga ◽  
Kei Mizuno ◽  
Tomohiro Katsumi ◽  
Chikako Sato ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Liver Regeneration ◽  
Progenitor Cells ◽  
Serum Levels ◽  
Dependent Manner ◽  
Portal Area ◽  
Injury Model

We have previously reported that epiregulin is a growth factor that seems to act on liver progenitor cells (LPCs) during liver regeneration. However, the relationship between epiregulin and LPCs has remained unclear. The aim of the present study was to clarify the role of epiregulin during liver regeneration. The serum levels of epiregulin in patients with acute liver failure were examined. A liver injury model was developed using mice fed a diet containing 0.1% 3.5-diethoxycarbonyl-1.4-dihydrocollidine (DDC) to induce LPCs. We then evaluated the expression of epiregulin and LPCs in these mice. The proliferation of epithelial cell adhesion molecule + LPCs cultured with epiregulin was examined in vitro, and finally epiregulin was overexpressed in mouse liver. In patients with acute liver failure, serum epiregulin levels were elevated significantly. In DDC mice, LPCs emerged around the portal area. Epiregulin was also detected around the portal area during the course of DDC-induced liver injury and was partially coexpressed with Thy1. Serum epiregulin levels in DDC mice were also significantly elevated. Recombinant epiregulin augmented the proliferative capacity of the LPCs in a dose-dependent manner. In mice showing overexpression of epiregulin, the expression of PCNA on hepatocytes was increased significantly. Finally, LPCs emerged around the portal area after epiregulin gene delivery. We concluded that epiregulin promotes the proliferation of LPCs and DNA synthesis by hepatocytes and is upregulated in the serum of patients with liver injury. Furthermore, induction of epiregulin leads to the appearance of LPCs. Epiregulin would be a useful biomarker of liver regeneration.

scholarly journals Tc-99m GSA scintigraphy within the first 3 days after admission as an early predictor of outcome in severe acute liver injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuji Suzuki ◽  
Keisuke Kakisaka ◽  
Takuro Sato ◽  
Ryouichi Mikami ◽  
Hiroaki Abe ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Acute Liver Injury ◽  
Area Under The Curve ◽  
Region Of Interest ◽  
Free Survival ◽  
Risk Of Death ◽  
Poor Outcome

AbstractPatients with severe acute liver injury (SLI) usually recover spontaneously. However, some SLI patients progress to acute liver failure with varying degrees of hepatic encephalopathy. Acute liver failure is associated with high mortality and can be substantially reduced by liver transplantation. Therefore, distinguishing SLI patients who might progress to acute liver failure and are at a risk of death is important when evaluating patients needing liver transplantation. The present study aimed to determine whether technetium-99m-diethylenetriaminepentaacetic acid galactosyl human serum albumin (Tc-99m GSA) scintigraphy can predict the prognosis of patients with SLI. This prospective observational study included 69 SLI patients. The accuracy of Tc-99m GSA for predicting death or liver transplantation for 6 months was assessed. Between the two groups of patients stratified based on the cut-off values from the receiver operating characteristic curves, 6-month transplant-free survival was compared. Sixteen (23.2%) patients died or underwent liver transplantation from admission (poor outcome). The hepatic accumulation index was calculated by dividing the radioactivity of the liver region of interest by that of the liver-plus-heart region of interest at 15 min (i.e., LHL15). The LHL15 in the 16 patients (0.686) was significantly lower than that in survivors (0.836; P < 0.0001). The optimal LHL15 cut-off for distinguishing poor outcome and survival was 0.737 with a sensitivity of 81.3%, specificity of 88.7%, and area under the curve of 0.907 (95% CI, 0.832–0.981). When patients were divided into two groups based on the LHL15 cut-off value, the 6-month transplant-free survival was significantly lower in patients with an LHL15 level ≤ 0.737. Tc-99m GSA scintigraphy may help predict the prognosis of patients with SLI.

Assay to detect inhibitors of liver regeneration in acute liver failure

1998 ◽  
Vol 28 ◽  
pp. 63
Author(s):  
C. Anderson ◽  
M.I. Thabrew ◽  
R.D. Hughes
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Liver Regeneration

Hepatoprotective effects of ginsenoside Rk3 in acetaminophen-induced liver injury in mice by activation of autophagy

2021 ◽  
Author(s):  
Linlin Qu ◽  
Rongzhan Fu ◽  
xiaoxuan Ma ◽  
Daidi Fan
Keyword(s):  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Acute Liver Injury ◽  
Common Causes ◽  
Hepatoprotective Effects

Acetaminophen (APAP)-induced acute liver injury (AIALI) is one of the most common causes of acute liver failure. Owing to the limitations of N-acetylcysteine (NAC), which is the only antidote currently...

Acute Fulminant Hepatic Failure in a Woman Treated With Phenytoin and Trimethoprim-Sulfamethoxazole

2000 ◽  
Vol 124 (12) ◽  
pp. 1800-1803 ◽  
Author(s):  
Marius J-M. Ilario ◽  
Jose E. Ruiz ◽  
Constantine A. Axiotis
Keyword(s):  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Fulminant Hepatic Failure ◽  
Hepatic Failure ◽  
Acute Hepatic Failure ◽  
Hepatic Necrosis ◽  
Rare Occurrence ◽  
Autopsy Findings ◽  
Massive Hepatic Necrosis

Abstract Massive hepatic necrosis following exposure to phenytoin and trimethoprim-sulfamethoxazole is a rare occurrence and to the best of our knowledge has not been reported previously. Acute hepatic failure following administration of trimethoprim-sulfamethoxazole has rarely been seen, and only 4 cases have been well documented pathologically. We report a case of acute liver failure in a 60-year-old woman following ingestion of phenytoin and trimethoprim-sulfamethoxazole concomitantly over a 9-day period. Autopsy findings revealed acute fulminant hepatic failure. This case demonstrates the effects of chemical-chemical interactions in the potentiation of hepatotoxicity of single agents and specifically illustrates the need for discontinuing trimethoprim-sulfamethoxazole in the presence of early liver injury.

scholarly journals Complement System as a Target for Therapies to Control Liver Regeneration/Damage in Acute Liver Failure Induced by Viral Hepatitis

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Juliana Gil Melgaço ◽  
Carlos Eduardo Veloso ◽  
Lúcio Filgueiras Pacheco-Moreira ◽  
Claudia Lamarca Vitral ◽  
Marcelo Alves Pinto
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Liver Regeneration ◽  
Viral Hepatitis ◽  
Complement System ◽  
Immune Cell ◽  
Ex Vivo ◽  
Heat Inactivation ◽  
Plasma Samples ◽  
The Complement System

The complement system plays an important role in innate immunity inducing liver diseases as well as signaling immune cell activation in local inflammation regulating immunomodulatory effects such as liver damage and/or liver regeneration. Our aim is to evaluate the role of complement components in acute liver failure (ALF) caused by viral hepatitis, involving virus-induced ALF in human subjects using peripheral blood, samples of liver tissues, and ex vivo assays. Our findings displayed low levels of C3a in plasma samples with high frequency of C3a, C5a, and C5b/9 deposition in liver parenchyma. Meanwhile, laboratory assays using HepG2 (hepatocyte cell line) showed susceptibility to plasma samples from ALF patients impairing in vitro cell proliferation and an increase in apoptotic events submitting plasma samples to heat inactivation. In summary, our data suggest that the complement system may be involved in liver dysfunction in viral-induced acute liver failure cases using ex vivo assays. In extension to our findings, we provide insights into future studies using animal models for viral-induced ALF, as well as other associated soluble components, which need further investigation.

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