TNF-α suppression by glutathione preconditioning attenuates hepatic ischemia reperfusion injury in young and aged rats

Arumugam, Suyavaran; Ramamurthy, Chitteti; Mareeswaran, Ramachandran; Subastri, Ariraman; Rao, Polaki Lokeswara; Thirunavukkarasu, Chinnasamy

doi:10.1007/s00011-014-0785-6

Cited by 25 publications

(23 citation statements)

References 58 publications

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“…The Western blotting of liver homogenate was performed to evaluate the expression patterns of inflammatory markers (TNF‐α, IL‐1β, N‐terminal cleavage fragment of PARP‐1), MAPK signals (ERK and P38MAPK), apoptotic markers (Caspase 8, Caspase 9, and Caspase 3), mitochondrial apoptosis regulators (Bcl‐xl, Bcl‐2, Bax, & Bad) and markers for neutrophil infiltration β‐2 integrin, macrophage inflammatory protein‐2 (MIP2), cytokine induced neutrophil chemoattractant‐2 (CINC1), and heme oxygenase‐1 (HO‐1) by previously described method (Suyavaran et al, ). The expressions were quantified by enhanced chemiluminescence reaction and analyzed by imageJ analysis software (NIH, Bethesda, Rockville, MD).…”

Section: Methodsmentioning

confidence: 99%

Neutrophil extracellular traps in acrolein promoted hepatic ischemia reperfusion injury: Therapeutic potential of NOX2 and p38MAPK inhibitors

Arumugam

Subbiah

Kemparaju³

et al. 2017

Journal Cellular Physiology

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Neutrophil is a significant contributor to ischemia reperfusion (IR) induced liver tissue damage. However, the exact role of neutrophils in IR induced innate immune activation and liver damage is not quite clear. Our study sheds light on the role of chronic oxidative stress end products in worsening the IR inflammatory process by neutrophil recruitment and activation following liver surgery. We employed specific inhibitors for molecular targets-NOX2 (NADPH oxidase 2) and P38 MAPK (Mitogen activated protein kinase) signal to counteract neutrophil activation and neutrophil extracellular trap (NET) release induced liver damage in IR injury. We found that acrolein initiated neutrophil chemotaxis and induced NET release both in vitro and in vivo. Acrolein exposure caused NET induced nuclear and mitochondrial damage in HepG2 cells as well as aggravated the IR injury in rat liver. Pretreatment with F-apocynin and naringin, efficiently suppressed acrolein induced NET release in vitro. Notably, it suppressed the expression of inflammatory cytokines, P38MAPK-ERK activation, and apoptotic signals in rat liver exposed to acrolein and subjected to IR. Moreover, this combination effectively attenuated acrolein induced NET release and hepatic IR injury. In the current study we have shown that the acrolein accumulation in liver due to chronic stress, is responsible for neutrophil recruitment and its activation leading to NET induced liver damage during surgery. Our study shows that therapeutic targeting of NOX2 and P38MAPK signaling in patients with chronic hepatic disorders would improve post operative hepatic function and survival.

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Section: Methodsmentioning

confidence: 99%

Neutrophil extracellular traps in acrolein promoted hepatic ischemia reperfusion injury: Therapeutic potential of NOX2 and p38MAPK inhibitors

Arumugam

Subbiah

Kemparaju³

et al. 2017

Journal Cellular Physiology

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“…With the progress of molecular science, the involvement of many cytokines has been determined. Closely related to cytokine involvement are the roles of hepatic nonparenchymal cells that have recently been reported [1-5]. Among the hepatic nonparenchymal cells, the HSC is thought to be the mechanically functioning cell that regulates sinusoidal diameters [22, 23], although its relationship with some special molecules acting in the inflammatory cytokine network is yet to be investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Kupffer cells, for example, have been shown to play an initial role in cytokine release during I/R [1-3], and the subsequent injury of sinusoidal endothelial cells, that is provoked by inflammatory cytokines as well as adhesion molecules, is the leading cause of hepatic microcirculatory disturbances thereafter [4, 5]. This vicious cycle adds further damage to I/R injury.…”

Section: Introductionmentioning

confidence: 99%

Hepatic Stellate Cells Play a Functional Role in Exacerbating Ischemia-Reperfusion Injury in Rat Liver

et al. 2019

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Purpose: The involvement of hepatic stellate cells (HSCs) with ischemia-reperfusion (I/R) injury in rat liver was examined using gliotoxin, which is known to induce HSC apoptosis. Methods: Male Sprague-Dawley rats were used. HSC was represented by a glial fibrillary acidic protein (GFAP)-positive cell. Liver ischemia was produced by cross-clamping the hepatoduodenal ligament. The degree of I/R injury was evaluated by a release of aminotransferases. Sinusoidal diameter and sinusoidal perfusion rates were examined using intravital fluorescence microscopy. Results: Gliotoxin significantly decreased the number of GFAP-positive cells 48 h after dosing (2.50 ± 0.19% [mean ± SD] in the nontreated group vs. 1.91 ± 0.46% in the gliotoxin-treated group). Liver damage was significantly suppressed by the pretreatment with gliotoxin. Sinusoidal diameters in zone 3 were wider in the gliotoxin group (10.25 ± 0.35 µm) than in the nontreated group (8.21 ± 0.50 µm). The sinusoidal perfusion rate was maintained as well in the gliotoxin group as in normal livers, even after I/R. Conclusions: Pretreatment with gliotoxin significantly reduced the number of HSCs in the liver and further suppressed liver injury following I/R. It is strongly suggested that HSCs play a functional role in exacerbating the degree of I/R injury of the liver.

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“…At the same time, endoplasmic reticulum (ER) stress of KCs in evoking liver inflammation following reperfusion contributed to the conversion of natural Tregs to Th17 cells due to IL-6 release, resulting in liver injury [151]. Whereas the inhibition of high-mobility group box 1 production by KCs after I/R in rats could prevent liver injury [152], suppression of TNF-α-mediated apoptotic signaling by glutathione (GSH) pretreatment can attenuate hepatic I/R injury in young and aged rats [153].…”

Section: Kupffer Cells In Liver Ischemia-reperfusion Injurymentioning

confidence: 99%

The Biological Function of Kupffer Cells in Liver Disease

Ma¹,

Yang²,

He³

et al. 2017

Biology of Myelomonocytic Cells

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Kupffer cells, which have a characteristic morphology and a kind of phenotype, are the resident macrophages in liver, serve as the largest population mononuclear phagocytes in the body, and are localized in the periportal zone. They have phagocytosis capacity and release all kinds of cytokines, chemokines, and soluble biological mediators. Owing to the different functions of Kupffer cells, they play an important role in liver diseases. In this chapter, we review the role of Kupffer cells in infectious disease, fatty liver disease, liver fibrosis, liver ischemia-reperfusion injury, liver transplantation immunology, as well as liver cancer and metastases.

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TNF-α suppression by glutathione preconditioning attenuates hepatic ischemia reperfusion injury in young and aged rats

Abstract: Restoration of GSH/GSSG ratio through GSH pre-conditioning inhibits TNF-α and apoptosis in hepatic I/R injury. Hence, GSH pre-conditioning may be utilized in both young and aged individuals during liver transplantation/surgery for better post-operative outcomes.

Cited by 25 publications

References 58 publications

Neutrophil extracellular traps in acrolein promoted hepatic ischemia reperfusion injury: Therapeutic potential of NOX2 and p38MAPK inhibitors

Neutrophil extracellular traps in acrolein promoted hepatic ischemia reperfusion injury: Therapeutic potential of NOX2 and p38MAPK inhibitors

Hepatic Stellate Cells Play a Functional Role in Exacerbating Ischemia-Reperfusion Injury in Rat Liver

The Biological Function of Kupffer Cells in Liver Disease

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