Interleukin 1 Receptor Blockade Reduces Tumor Necrosis Factor Production, Tissue Injury, and Mortality After Hepatic Ischemia-Reperfusion in the Rat1

Shito, Masaya; Wakabayashi, Go; Ueda, Masafumi; Shimazu, Motohide; Shirasugi, Nozomu; Endo, Makoto; Mukai, Manabu; Kitajima, Masaki

doi:10.1097/00007890-199701150-00026

Cited by 142 publications

(93 citation statements)

References 31 publications

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“…26 IL-1 induces Kupffer cells to produce TNF-␣ and also upregulates free radical production. The role of both cytokines is further confirmed by experiments in which their neutralization decreased severity of reperfusion injury, as evidenced by decreased PMN infiltration and reduced damage to the parenchyma, 27 the same effects we have achieved with BV therapy. Recently, a putative mechanism through which IL-1␤ is able to stimulate iNOS expression in hepatocytes has been proposed.…”

Section: Discussionsupporting

confidence: 75%

Biliverdin therapy protects rat livers from ischemia and reperfusion injury

et al. 2004

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Heme oxygenase (HO-1) provides a cellular defense mechanism during oxidative stress and catalyzes the rate-limiting step in heme metabolism that produces biliverdin (BV). The role of BV and its potential use in preventing ischemia/reperfusion injury (IRI) had never been studied. This study was designed to explore putative cytoprotective functions of BV during hepatic IRI in rat liver models of ex vivo perfusion and orthotopic liver transplantation (OLT) after prolonged periods of cold ischemia. In an ex vivo hepatic IRI model, adjunctive BV improved portal venous blood flow, increased bile production, and decreased hepatocellular damage. These findings were correlated with amelioration of histological features of IRI, as assessed by Suzuki's criteria. Following cold ischemia and syngeneic OLT, BV therapy extended animal survival from 50% in untreated controls to 90% to 100%. This effect correlated with improved liver function and preserved hepatic architecture. Additionally, BV adjuvant after OLT decreased endothelial expression of cellular adhesion molecules (P-selectin and intracellular adhesion molecule 1), and decreased the extent of infiltration by neutrophils and inflammatory macrophages. BV also inhibited expression of inducible nitric oxide synthase and proinflammatory cytokines (interleukin 1␤, tumor necrosis factor ␣, and interleukin 6) in OLTs. Finally, BV therapy promoted an increased expression of antiapoptotic molecules independently of HO-1 expression, consistent with BV being an important mediator through which HO-1 prevents cell death. In conclusion, this study documents and dissects potent cytoprotective effects of BV in well-established rat models of hepatic IRI. Our results provide the rationale for a novel therapeutic approach using BV to maximize the function and thus the availability of donor organs. (HEPATOLOGY 2004;40:1333-1341 I schemia and reperfusion injury (IRI), an antigen-independent component of the insult to the liver during "harvesting," represents an important problem affecting liver transplantation. IRI causes up to 10% of early liver failures and can lead to a higher incidence of acute and chronic rejection. 1 Moreover, with the increasing donor shortage, more functionally "suboptimal" or "marginal" livers are being used. Such livers are more susceptible to the damage caused by IRI compared with normal livers. 2 Indeed, minimizing the adverse effects of IRI could significantly increase the number of patients that successfully undergo liver transplantation.Liver IRI is mediated by several processes that lead to hepatocellular damage, which is triggered when the liver is transiently deprived of oxygen during the organ procurement for transplantation, and later reoxygenated during reperfusion. The structural changes promoted by cold ischemia and reperfusion become more prominent with increased storage time. 3 The sinusoidal endothelial cells are very sensitive to IRI, thus affecting the delicate balance that maintains homeostasis in the microcirculation with

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Section: Discussionsupporting

confidence: 75%

Biliverdin therapy protects rat livers from ischemia and reperfusion injury

et al. 2004

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“…16 Interleukin 1β can stimulate the production of TNF-α, while inducing the aggregation of neutrophils by upregulating expression of intercellular adhesion molecule 1. 17 In our study, TNF-α and IL-1β levels significantly increased after 1 hour of reperfusion when hepatic injury was not so severe. However, when injury became quite severe at 6 hours, TNF-α and IL-1β levels decreased.…”

Section: Discussionsupporting

confidence: 50%

Untitled

2016

Exp Clin Transplant

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Objectives: Our objective was to evaluate the effects of contrast-enhanced ultrasonography in monitoring microcirculation after rat liver ischemia-reperfusion injury. Materials and Methods: Male Wistar rats (n = 36) were divided into sham-operated and ischemia-reperfusion groups. Rats in the ischemia-reperfusion groups underwent normothermic liver ischemia for 15 minutes followed by 1, 6, or 24 hours of reperfusion. At different time points, contrast-enhanced ultrasonography was performed to determine peak intensity in monitoring hepatic microcirculation. In addition, serum levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor α, and interleukin 1β levels were measured. Histopathologic changes were also observed. Results: One hour after reperfusion, peak intensity values decreased, and serum levels of alanine aminotransferase, tumor necrosis factor α, and interleukin 1β increased significantly in the ischemiareperfusion group compared with the sham-operated group. Histology results showed mild injury. Six hours after reperfusion, peak intensity values decreased continuously, serum levels of alanine aminotransferase, tumor necrosis factor α, and interleukin 1β decreased, and aspartate aminotransferase levels increased. Histology results showed severe injury compared with 1 hour after reperfusion. Twenty-four hours after reperfusion, peak intensity values increased, alanine aminotransferase and aspartate aminotransferase levels decreased, and histology results showed moderate injury compared with 6 hours after reperfusion. Peak intensity values were negatively correlated to alanine aminotransferase (P < .05; γ = -0.38) and aspartate aminotransferase (P < .01; γ = -0.78) levels. Conclusions: Microcirculation dysfunction after liver ischemia-reperfusion injury can be monitored by contrast-enhanced ultrasonography. The perfusion of contrast agents negatively correlates to the severity of injuries.

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“…In other studies with similar models, the IL-1 receptor blockade was shown to decrease tissue damage and thus decrease mortality (16,17). This evidence suggests that the anesthetic agent that greatly prevents the increase in TNF-α, IL-1, and MDA levels will have the best protective effects against tissue damage.…”

Section: Discussionmentioning

confidence: 80%