Hepatic protection by glycyrrhizin and inhibition of iNOS expression in concanavalin A-induced liver injury in mice

Tsuruoka, Noriko; Abe, Kazuki; Wake, Kenjirou; Takata, Masaru; Hatta, Akira; Sato, Tositugu; Inoue, Hideo

doi:10.1007/s00011-009-0024-8

Cited by 33 publications

(22 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, the production of NO and the expression of iNOS in lung tissues increased significantly after LPS administration, which were markedly inhibited by GL pretreatment in a dose-dependent manner. These effects are in agreement with the study, indicating that GL attenuated concanavalin A-induced acute liver injury by reducing the expression of iNOS mRNA and protein [16]. Likewise, in the animal model of acute liver injury induced by carbon tetrachloride, the increase in iNOS protein level was significantly attenuated by GL treatment [19].…”

Section: Discussionsupporting

confidence: 92%

See 1 more Smart Citation

Glycyrrhizin Treatment Is Associated with Attenuation of Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting Cyclooxygenase-2 and Inducible Nitric Oxide Synthase Expression

Kuai

et al. 2011

Journal of Surgical Research

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 92%

“…It has been attributed to numerous pharmacologic effects like anti-inflammatory, antiviral, anti-tumor, and hepatoprotective activities [14]. It has been shown that GL inhibited the inflammation in mice model of liver injury [15,16]. To date, unfortunately, the protective role of GL in ALI is not well characterized.…”

Section: Introductionmentioning

confidence: 97%

Glycyrrhizin Treatment Is Associated with Attenuation of Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting Cyclooxygenase-2 and Inducible Nitric Oxide Synthase Expression

Kuai

et al. 2011

Journal of Surgical Research

View full text Add to dashboard Cite

“…Further, HIF-1α upregulates iNOS expression leading to nitric oxide production which is necessary for pro-inflammatory macrophage function 56 . Accordingly, nitric oxide has a well-described role in perpetuating Con-A-induced liver injury 57, 58 . Our data suggests that pharmacologic blockade of C/EBPβ and HIF-1α is protective in Con-A hepatitis and is associated with decreased iNOS expression in various leukocyte subtypes.…”

Section: Discussionmentioning

confidence: 99%

Mincle Signaling Promotes Con A Hepatitis

Greco

Torres‐Hernandez

Kalabin

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

Concanavalin-A (Con-A) hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor (CLR) that is critical in the immune response to mycobacteria and fungi, but does not have a well-defined role in pre-clinical models of non-pathogen mediated inflammation. Since Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con-A hepatitis. Acute liver injury was assessed in the murine Con-A hepatitis model using C57BL/6, Mincle−/−, and Dectin-1−/− mice. The role of C/EBPβ and HIF-1α signaling was assessed using selective inhibitors. We found that Mincle was highly expressed in hepatic innate inflammatory cells and endothelial cells in both mice and humans. Furthermore, sterile Mincle ligands and Mincle signaling intermediates were increased in the murine liver in Con-A hepatitis. Most significantly, Mincle deletion or blockade protected against Con-A hepatitis whereas Mincle ligation exacerbated disease. Bone marrow chimeric and adoptive transfer experiments suggested that Mincle signaling in infiltrating myeloid cells dictates disease phenotype. Conversely, signaling via other CLRs did not alter disease course. Mechanistically, we found that Mincle blockade decreased the NF-κβ related signaling intermediates, C/EBPβ and HIF-1α, both of which are necessary in macrophage-mediated inflammatory responses. Accordingly, Mincle deletion lowered production of nitrites in Con-A hepatitis and inhibition of both C/EBPβ and HIF1-α reduced the severity of liver disease. Our work implicates a novel innate immune driver of Con-A hepatitis and, more broadly, suggests a potential role for Mincle in diseases governed by sterile inflammation.

show abstract

“…The NF-κB is a transcription factor that promotes the expression of pro-inflammatory genes that activate immune responses 46 . The roles of iNOs, PAI-1, and MCP-1 are involved in Con A-mediated hepatitis 47–49 . Therefore, the expressions of these inflammatory cytokines in our studies demonstrated that the condition of aging is more susceptible to immunosenescence-mediated inflammatory injury in livers challenged with Con A.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Pretreatment Attenuates Concanavalin A-induced Hepatitis through Reverse of Aberration in the Immune Response and Regenerative Capacity in Aged Mice

Huang

Chen

Liu³

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Loss of regenerative capacity plays a critical role in age-related autoimmune hepatitis. Evidence implicates SIRT1 and p66shc in cell senescence, apoptosis, oxidative stress, and proliferation. This study investigated the effect of resveratrol on concanavalin A (Con A)-induced hepatitis in aged mice and the roles of SIRT1 and p66shc. Aged mice were administrated resveratrol (30 mg/kg orally) seven times at an interval of 12 h before a single intravenous injection of Con A (20 mg/kg). Results showed that the cytokines, TNF-α, IL-6, IFN-γ, and MCP-1, as well as infiltration of macrophages, neutrophils, and T lymphocytes in liver were dramatically enhanced in the mice given only Con A. The aged mouse livers showed markedly raised oxidative stress and cell apoptosis. This oxidative stress further aggravated regenerative dysfunction as indicated by the decreased levels of Ki67, PCNA, Cyclin D1, and Cdk2. Conversely, these phenomena were attenuated by pretreatment with resveratrol. Moreover, resveratrol suppressed the elevation of p66shc in the liver by reversing Con-A-mediated downregulation of SIRT1. The findings suggest that resveratrol protected against Con A-induced hepatitis in aged mice by attenuating an aberration of immune response and liver regeneration, partially via the mechanism of SIRT1-mediated repression of p66shc expression.

show abstract

Hepatic protection by glycyrrhizin and inhibition of iNOS expression in concanavalin A-induced liver injury in mice

Abstract: The present study suggests that the prevention by GL of Con A-induced hepatitis is due partly to the modulation of hepatic iNOS induction and of degeneration of hepatocytes.

Cited by 33 publications

References 31 publications

Glycyrrhizin Treatment Is Associated with Attenuation of Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting Cyclooxygenase-2 and Inducible Nitric Oxide Synthase Expression

Glycyrrhizin Treatment Is Associated with Attenuation of Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting Cyclooxygenase-2 and Inducible Nitric Oxide Synthase Expression

Mincle Signaling Promotes Con A Hepatitis

Resveratrol Pretreatment Attenuates Concanavalin A-induced Hepatitis through Reverse of Aberration in the Immune Response and Regenerative Capacity in Aged Mice

Contact Info

Product

Resources

About