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Hepatic Ischemia (hepatic + ischemia)
Selected AbstractsMethimazole protects lungs during hepatic ischemia,reperfusion injury in rats: An effect not induced by hypothyroidismJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2007Tanju Tütüncü Abstract Background:, Hepatic ischemia,reperfusion injury may lead to remote organ failure with mortal respiratory dysfunction. The aim of the present study was to analyze the possible protective effects of methimazole on lungs after hepatic ischemia,reperfusion injury. Methods:, Forty male Wistar albino rats were randomized into five groups: a control group, in which bilateral pulmonary lobectomy was done; a hepatic ischemia,reperfusion group, in which bilateral pulmonary lobectomy was done after hepatic ischemia,reperfusion; a thyroidectomy,ischemia,reperfusion group (total thyroidectomy followed by, 7 days later, bilateral pulmonary lobectomy after hepatic ischemia,reperfusion); a methimazole,ischemia,reperfusion group (following methimazole administration for 7 days, bilateral pulmonary lobectomy was done after hepatic ischemia,reperfusion); and a methimazole +l -thyroxine,ischemia,reperfusion group (following methimazole and l -thyroxine administration for 7 days, bilateral pulmonary lobectomy was performed after hepatic ischemia,reperfusion). Pulmonary tissue specimens were evaluated histopathologically and for myeloperoxidase and malondialdehyde levels. Results:, All of the ischemia,reperfusion intervention groups had higher pulmonary injury scoring indices than the control group (P < 0.001). Pulmonary injury index of the ischemia,reperfusion group was higher than that of both the methimazole-supplemented hypothyroid and euthyroid groups (P = 0028; P = 0,038, respectively) and was similar to that of the thyroidectomized group. Pulmonary tissue myeloperoxidase and malondialdehyde levels in the ischemia,reperfusion group were similar with that in the thyroidectomized rats but were significantly higher than that in the control, and both the methimazole-supplemented hypothyroid and euthyroid groups. Conclusion:, Methimazole exerts a protective role on lungs during hepatic ischemia,reperfusion injury, which can be attributed to its anti-inflammatory and anti-oxidant effects rather than hypothyroidism alone. [source] Interleukin 18 causes hepatic ischemia/reperfusion injury by suppressing anti-inflammatory cytokine expression in miceHEPATOLOGY, Issue 3 2004Dan Takeuchi Hepatic ischemia/reperfusion injury is a clinically important problem. While the mechanisms of the initial event and subsequent neutrophil-dependent injury are somewhat understood, little is known about the regulation of endogenous hepatoprotective effects on this injury. Interleukin 12 (IL-12) plays a role in the induction of this injury, but involvement of interleukin 18 (IL-18) has not been clarified. Using a murine model of partial hepatic ischemia and subsequent reperfusion, the aim of the current study was to determine whether IL-18 is up-regulated during hepatic ischemia/reperfusion and to determine the role of endogenous IL-18 in the development and regulation of inflammatory hepatic ischemia/reperfusion injury. Hepatic IL-18 expression was up-regulated from 1 to 8 hours after reperfusion. Hepatic ischemia/reperfusion induced nuclear factor-,B (NF-,B) and activator protein 1 (AP-1) activation, as defined by electrophoretic mobility shift assay, and caused significant increases in liver neutrophil recruitment, apoptosis, hepatocellular injury, and liver edema as defined by liver myeloperoxidase content, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end-labeling (TUNEL) staining, serum aminotransferase levels, and liver wet-to-dry weight ratios. In mice treated with neutralizing antibody to IL-18, ischemia/reperfusion-induced increases in CXC chemokine expression, activation of NF-,B and AP-1, and apoptosis were greatly reduced. Furthermore, under blockade of IL-18, anti-inflammatory cytokines such as IL-4 and IL-10 were greatly up-regulated. Signal transducer and activator of transcription 6 (STAT6) was significantly activated under blockade of IL-18. These conditions also caused significant reduction in liver neutrophil sequestration and liver injury. In conclusion, the data suggest that IL-18 is required for facilitating neutrophil-dependent hepatic ischemia/reperfusion injury through suppressing anti-inflammatory cytokine expression. (HEPATOLOGY 2004;39:699,710.) [source] Low-dose TNF-, protects against hepatic ischemia-reperfusion injury in mice: Implications for preconditioningHEPATOLOGY, Issue 1 2003Narci Teoh Tumor necrosis factor , (TNF-,) is implicated in the pathogenesis of hepatic ischemia reperfusion injury but can also prime hepatocytes to enter the cell cycle. Ischemic preconditioning protects against ischemia-reperfusion (IR) liver injury and is associated with activation of nuclear factor ,B (NF-,B) and cell cycle entry. We examined the pattern of TNF-, release during hepatic IR in the presence or absence of ischemic preconditioning, and we tested whether a single low-dose injection of TNF could mimic the biologic effects of ischemic preconditioning. In naďve mice, hepatic and plasma levels of TNF-, rose during hepatic ischemia, reaching high levels after 90 minutes; values remained elevated during reperfusion until 44 hours. Following the ischemic preconditioning stimulus, there was an early rise in hepatic and serum TNF-, levels, but, during a second prolonged ischemic interval peak, TNF-, values were lower than in naďve mice and declined to negligible levels by 2 hours reperfusion. An injection with 1 ,g or 5 ,g/kg body weight TNF-, 30 minutes prior to hepatic IR substantially reduced liver injury determined by liver histology and serum alanine aminotransferase (ALT) levels. As in ischemic preconditioning, TNF-, pretreatment activated NF-,B DNA binding, STAT3, cyclin D1, cyclin-dependent kinase 4 (cdk4) expression, and cell cycle entry, determined by proliferating cell nuclear antigen (PCNA) staining of hepatocyte nuclei. In conclusion, the hepatoprotective effects of "preconditioning" can be simulated by TNF-, injection, which has identical downstream effects on cell cycle entry. We propose that transient increases in TNF-, levels may substitute for, as well as, mediate the hepatoprotective effects of ischemic preconditioning against hepatic IR injury. [source] Methimazole protects lungs during hepatic ischemia,reperfusion injury in rats: An effect not induced by hypothyroidismJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2007Tanju Tütüncü Abstract Background:, Hepatic ischemia,reperfusion injury may lead to remote organ failure with mortal respiratory dysfunction. The aim of the present study was to analyze the possible protective effects of methimazole on lungs after hepatic ischemia,reperfusion injury. Methods:, Forty male Wistar albino rats were randomized into five groups: a control group, in which bilateral pulmonary lobectomy was done; a hepatic ischemia,reperfusion group, in which bilateral pulmonary lobectomy was done after hepatic ischemia,reperfusion; a thyroidectomy,ischemia,reperfusion group (total thyroidectomy followed by, 7 days later, bilateral pulmonary lobectomy after hepatic ischemia,reperfusion); a methimazole,ischemia,reperfusion group (following methimazole administration for 7 days, bilateral pulmonary lobectomy was done after hepatic ischemia,reperfusion); and a methimazole +l -thyroxine,ischemia,reperfusion group (following methimazole and l -thyroxine administration for 7 days, bilateral pulmonary lobectomy was performed after hepatic ischemia,reperfusion). Pulmonary tissue specimens were evaluated histopathologically and for myeloperoxidase and malondialdehyde levels. Results:, All of the ischemia,reperfusion intervention groups had higher pulmonary injury scoring indices than the control group (P < 0.001). Pulmonary injury index of the ischemia,reperfusion group was higher than that of both the methimazole-supplemented hypothyroid and euthyroid groups (P = 0028; P = 0,038, respectively) and was similar to that of the thyroidectomized group. Pulmonary tissue myeloperoxidase and malondialdehyde levels in the ischemia,reperfusion group were similar with that in the thyroidectomized rats but were significantly higher than that in the control, and both the methimazole-supplemented hypothyroid and euthyroid groups. Conclusion:, Methimazole exerts a protective role on lungs during hepatic ischemia,reperfusion injury, which can be attributed to its anti-inflammatory and anti-oxidant effects rather than hypothyroidism alone. [source] A20 protects mice from lethal liver ischemia/reperfusion injury by increasing peroxisome proliferator-activated receptor-, expressionLIVER TRANSPLANTATION, Issue 11 2009Haley E. Ramsey The nuclear factor-,B inhibitory protein A20 demonstrates hepatoprotective abilities through combined antiapoptotic, anti-inflammatory, and pro-proliferative functions. Accordingly, overexpression of A20 in the liver protects mice from toxic hepatitis and lethal radical hepatectomy, whereas A20 knockout mice die prematurely from unfettered liver inflammation. The effect of A20 on oxidative liver damage, as seen in ischemia/reperfusion injury (IRI), is unknown. In this work, we evaluated the effects of A20 upon IRI using a mouse model of total hepatic ischemia. Hepatic overexpression of A20 was achieved by recombinant adenovirus (rAd.)-mediated gene transfer. Although only 10%-25% of control mice injected with saline or the control rAd., galactosidase survived IRI, the survival rate reached 67% in mice treated with rAd.A20. This significant survival advantage in rAd.A20-treated mice was associated with improved liver function, pathology, and repair potential. A20-treated mice had significantly lower bilirubin and aminotransferase levels, decreased hemorrhagic necrosis and steatosis, and increased hepatocyte proliferation. A20 protected against liver IRI by increasing hepatic expression of peroxisome proliferator-activated receptor alpha (PPAR,), a regulator of lipid homeostasis and of oxidative damage. A20-mediated protection of hepatocytes from hypoxia/reoxygenation and H2O2 -mediated necrosis was reverted by pretreatment with the PPAR, inhibitor MK886. In conclusion, we demonstrate that PPAR, is a novel target for A20 in hepatocytes, underscoring its novel protective effect against oxidative necrosis. By combining hepatocyte protection from necrosis and promotion of proliferation, A20-based therapies are well-poised to protect livers from IRI, especially in the context of small-for-size and steatotic liver grafts. Liver Transpl 15:1613,1621, 2009. © 2009 AASLD. [source] Ischemic preconditioning and intermittent clamping improve murine hepatic microcirculation and Kupffer cell function after ischemic injuryLIVER TRANSPLANTATION, Issue 4 2004Katarína Vajdová The aim of this study was to evaluate whether the protective effect of intermittent clamping and ischemic preconditioning is related to an improved hepatic microcirculation after ischemia/reperfusion injury. Male C57BL/6 mice were subjected to 75 or 120 min of hepatic ischemia and 1 or 3 hours of reperfusion. The effects of continuous ischemia, intermittent clamping, and ischemic preconditioning before prolonged ischemia on sinusoidal perfusion, leukocyte-endothelial interactions, and Kupffer cell phagocytic activity were analyzed by intravital fluorescence microscopy. Kupffer cell activation was measured by tissue levels of tumor necrosis factor (TNF)-,, and the integrity of sinusoidal endothelial cells and Kupffer cells were evaluated by electron microscopy. Continuous ischemia resulted in decreased sinusoidal perfusion rate and phagocytic activity of Kupffer cell, increased leukocyte-endothelial interactions and TNF-, levels. Both protective strategies improved sinusoidal perfusion, leukocyte-endothelial interactions and phagocytic activity of Kupffer cells after 75-minutes of ischemia, and intermittent clamping also after 120 minutes ischemia. TNF-, release was significantly reduced and sinusoidal wall integrity was preserved by both protective procedures. In conclusion, both strategies are protective against ischemia/reperfusion injury by maintaining hepatic microcirculation and decreasing Kupffer cell activation for clinically relevant ischemic periods, and intermittent clamping appears superior for prolonged ischemia. (Liver Transpl 2004;10:520,528.) [source] Hyperbaric oxygen therapy protects the liver from apoptosis caused by ischemia-reperfusion injury in ratsMICROSURGERY, Issue 7 2009José C. Chaves M.D., M.Sc. Purpose: The present paper aimed to investigate the role of hyperbaric oxygen treatment (HBO) and the apoptosis in rat liver ischemia-reperfusion injury (IRI). Methods: Thirty-seven male Wistar rats were subjected to 30 minutes of hepatic ischemia and 30 minutes of reperfusion and randomly distributed into six groups: G-I/R (n = 8), control without HBO; G-HBO/I (n = 8), HBO only during the ischemia period; G-HBO/R (n = 8), HBO only during the reperfusion period; G-HBO-I/R (n = 8), HBO during both the ischemia and reperfusion periods; G-Sh (n = 3), HBO without ischemia or reperfusion as sham group; G-C (n = 2) for control of current apoptosis expression on the normal liver tissue. HBO was carried out using a transparent, cylindrical acrylic chamber with a pressure of 2.0 ATA. Hepatic samples were stained for caspase-3 cleavage. Results: Apoptotic cells were identified in all groups. In the hepatic specimens of animals HBO-treated during ischemia (GHBO-I), there was a significant decrease (P < 0.001) in the number of cells undergoing apoptosis (1.62 ± 0.91). The apoptotic index showed no significant difference in the animals HBO-treated during ischemia/reperfusion (5.75 ± 1.28) compared with the G-I/R (3.5 ± 0.75), which had no HBO treatment. The apoptosis index (11.25 ± 1.90) was significantly higher (P < 0.01) in HBO-treated animals during the reperfusion period when compared with any of the other groups. Conclusion: A favorable effect was obtained when hyperbaric oxygen was administered early during ischemia. The hyperbaric oxygen in later periods of reperfusion was associated with a more severe apoptosis index. © 2009 Wiley-Liss, Inc. Microsurgery 2009. [source] Cytoprotective Effects of a Cyclic RGD Peptide in Steatotic Liver Cold Ischemia and Reperfusion InjuryAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009C. Fondevila The serious need for expanding the donor population has attracted attention to the use of steatotic donor livers in orthotopic liver transplantation (OLT). However, steatotic livers are highly susceptible to hepatic ischemia,reperfusion injury (IRI). Expression of fibronectin (FN) by endothelial cells is an important feature of hepatic response to injury. We report the effect of a cyclic RGD peptide with high affinity for the ,5,1, the FN integrin receptor, in a rat model of steatotic liver cold ischemia, followed by transplantation. RGD peptide therapy ameliorated steatotic IRI and improved the recipient survival rate. It significantly inhibited the recruitment of monocyte/macrophages and neutrophils, and depressed the expression of pro-inflammatory mediators, such as inducible nitric oxide synthase (iNOS) and interferon (IFN)-,. Moreover, it resulted in profound inhibition of metalloproteinase-9 (MMP-9) expression, a gelatinase implied in leukocyte migration in damaged livers. Finally, we show that RGD peptide therapy reduced the expression of the 17-kDa active caspase-3 and the number of apoptotic cells in steatotic OLTs. The observed protection against steatotic liver IRI by the cyclic RGD peptides with high affinity for the ,5,1 integrin suggests that this integrin is a potential therapeutic target to allow the successful utilization of marginal steatotic livers in transplantation. [source] | ||||||||||