Focal liver necrosis appears early after partial hepatectomy and is dependent on T cells and antigen delivery from the gut

Rudich, Noam; Zamir, Gideon; Pappo, Orit; Shlomai, Zipora; Faroja, Muhamad; Weiss, Ido D.; Wald, Hanna; Galun, Eithan; Peled, Amnon; Wald, Ori

doi:10.1111/j.1478-3231.2009.02048.x

Cited by 20 publications

(15 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After mice were euthanized, the livers were removed and small pieces from different lobes of the livers were fixed in 10% neutral buffered formalin, embedded in paraffin, sectioned at 5 μM, and stained with hematoxylin and eosin (H&E) for necrosis and other structural changes. The degree of tissue necrosis was evaluated and scored as previously reported (Rudich et al, 2009). The necrotic score indicated the number of necrotic foci per low-power magnification field (×100) in at least 10 fields per slide.…”

Section: Methodsmentioning

confidence: 99%

Alisol B 23-acetate protects against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes involved in bile acid homeostasis

Meng

Chen

Wang

et al. 2015

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

Section: Methodsmentioning

confidence: 99%

Alisol B 23-acetate protects against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes involved in bile acid homeostasis

Meng

Chen

Wang

et al. 2015

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

“…LPS as a toll-like receptor 4 ligand has been reported to play a central role in the initiation of liver regeneration [23, 24]. Rudich et al even found reduced hepatocyte proliferation in partial hepatectomized mice after removing LPS from the gut via antibiotic pretreatment [25]. In addition, hepatocyte-specific deletion of NEMO, the regulatory subunit of the NF-κB complex, leads to impaired liver regeneration after partial hepatectomy independent of an inflammation [26].…”

Section: Discussionmentioning

confidence: 99%

“…A moderate inflammatory stimulus seems to be essential for the initiation of liver regeneration, whereas marked inflammatory reactions have a negative impact [27, 28]. Thus, complete elimination of LPS via antibiotic bowel decontamination [25] prevents the stimulatory effect. Tail vein injection of LPS in rats [29] or intraperitoneally application in mice induces the accumulation of neutrophils in the liver [30].…”

Section: Discussionmentioning

confidence: 99%

Impact of NKT Cells and LFA-1 on Liver Regeneration under Subseptic Conditions

et al. 2016

View full text Add to dashboard Cite

BackgroundActivation of the immune system in terms of subseptic conditions during liver regeneration is of paramount clinical importance. However, little is known about molecular mechanisms and their mediators that control hepatocyte proliferation. We sought to determine the functional role of immune cells, especially NKT cells, in response to partial hepatectomy (PH), and to uncover the impact of the integrin lymphocyte function-associated antigen-1 (LFA-1) on liver regeneration in a subseptic setting.MethodsWild-type (WT) and LFA-1-/- mice underwent a 2/3 PH and low-dose lipopolysaccharid (LPS) application. Hepatocyte proliferation, immune cell infiltration, and cytokine profile in the liver parenchyma were determined.ResultsLow-dose LPS application after PH results in a significant delay of liver regeneration between 48h and 72h, which is associated with a reduced number of CD3+ cells within the regenerating liver. In absence of LFA-1, an impaired regenerative capacity was observed under low-dose LPS application. Analysis of different leukocyte subpopulations showed less CD3+NK1.1+ NKT cells in the liver parenchyma of LFA-1-/- mice after PH and LPS application compared to WT controls, while CD3-NK1.1+ NK cells markedly increased. Concordantly with this observation, lower levels of NKT cell related cytokines IL-12 and IL-23 were expressed in the regenerating liver of LFA-1-/- mice, while the expression of NK cell-associated CCL5 and IL-10 was increased compared to WT mice.ConclusionA subseptic situation negatively alters hepatocyte proliferation. Within this scenario, we suggest an important impact of NKT cells and postulate a critical function for LFA-1 during processes of liver regeneration.

show abstract

“…Focal and/or patchy necrosis is an important finding after hepatectomy 24–27 . Progressive necrosis was confirmed from the early postoperative period, 24,25,27 and we collected all samples at 6 h after 90% hepatectomy. There were eight mice in each group.…”

Section: Methodsmentioning

confidence: 99%

Effect of specific activation of γ‐aminobutyric acid receptor in vivo on oxidative stress‐induced damage after extended hepatectomy

Gardner¹,

Hori

Chen³

et al. 2012

Hepatology Research

View full text Add to dashboard Cite

Aim Gamma-aminobutyric acid (GABA) is a multifunctional molecule with various physiological effects throughout the body. The regulation of GABA receptor (GABAR) plays a key role in reducing the damage mediated by oxidative stress (OS). Extended hepatectomy causes fatal OS-induced injury in the liver remnant. We aimed to investigate the effect of a GABAR agonist in extended hepatectomy. Methods Saline or a GABAR agonist (43.56 nmol/g body weight of muscimol) was given intravenously at 4 h preoperatively. C57BL/6 mice were divided into three groups: laparotomy only, 90% hepatectomy with saline and 90% hepatectomy with a GABAR agonist. Liver samples were obtained at 6 h after surgery. Results Survival curves were prolonged by the GABAR agonist. Histopathological findings and biochemical profiles showed that the GABAR agonist reduced liver damage. Immunohistological assessment demonstrated that the GABAR agonist prevented apoptotic induction. As shown by 4-hydroxynonenal, which reflects OS-induced damage, 90% hepatectomy caused OS and the GABAR agonist reduced OS. We measured ATM, H2AX, Akt and free radical scavenging enzymes since they may be affected by GABAR regulation, and found that Akt was greatly decreased after 90% hepatectomy, but it recovered with the GABAR agonist. Conclusions GABAR is activated by a specific agonist in the liver in vivo. This activation reduces OS-madiated damage after extended hepatectomy in vivo, and the mechanism via an Akt-dependent pathway may be a key.

show abstract

Focal liver necrosis appears early after partial hepatectomy and is dependent on T cells and antigen delivery from the gut

Cited by 20 publications

References 32 publications

Alisol B 23-acetate protects against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes involved in bile acid homeostasis

Alisol B 23-acetate protects against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes involved in bile acid homeostasis

Impact of NKT Cells and LFA-1 on Liver Regeneration under Subseptic Conditions

Effect of specific activation of γ‐aminobutyric acid receptor in vivo on oxidative stress‐induced damage after extended hepatectomy

Contact Info

Product

Resources

About