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Sinusoidal Endothelial Cell Injury (sinusoidal + endothelial_cell_injury)
Selected AbstractsRole of neutrophils in sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic ratsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2000Masayuki Ohtsuka Abstract Background and Aims: The authors have shown previously that sinusoidal endothelial cell injury developed concomitantly with the accumulation of neutrophils in the hepatic sinusoidal space in cholestatic rats after extensive hepatectomy. The aim of the present study was to investigate the role of neutrophils in the development of this kind of endothelial cell injury. Methods: Rats underwent 78% partial hepatectomy after 2 weeks of cholestasis, and subsequent external biliary drainage for 5 days. To decrease the number of neutrophils, antirat neutrophil serum was administered intraperitoneally. Some serum parameters and histological specimens were examined 48 h after partial hepatectomy. Results: Anti-neutrophil serum significantly reduced the number of accumulated neutrophils in the hepatic sinusoids. Although the purine nucleoside phosphorylase : alanine aminotransferase ratio, a marker of non-parenchymal cell injury, was increased in cholestatic-hepatectomized rats, this abnormality was significantly attenuated by the treatment with antineutrophil serum. Electron microscopically, focal detachment of cytoplasms of sinusoidal endothelial cells was observed occasionally in cholestatic-hepatectomized rats, but was not found in the antirat neutrophil serum-treated rats. Conclusion: These results indicate that accumulated neutrophils might be important effector cells in the pathogenesis of sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats, even after appropriate external biliary drainage. [source] Red blood cells attenuate sinusoidal endothelial cell injury by scavenging xanthine oxidase-dependent hydrogen peroxide in hyperoxic perfused rat liverLIVER INTERNATIONAL, Issue 3 2000Satoru Motoyama Abstract:Aims/Background: Rat liver perfused with an oxygenated buffered solution alone results in degenerative changes even when the perfusion flow is accelerated to give a sufficient oxygen supply. On the other hand, perfusion media supplemented with red blood cells (RBCs) preserve the viability of the liver. The present study was conducted to clarify how RBCs protect the isolated perfused liver. Methods: The liver was perfused with and without RBCs in a perfusate equilibrated with supra-physiological oxygen tension at regulated inflow pressures, and controlled hepatic oxygen consumption. We examined alanine aminotransferase and purine nucleoside phosphorylase activity in the perfusate as specific markers of liver cells injury. Hydrogen peroxide (H2O2) production and morphological changes were determined using cerium electron microscopy. Apoptosis was detected by measuring CPP 32 protease activity and using TdT-mediated dUTP-digoxigenin nick end-labeling. Results: When the liver was perfused with RBC-free buffer, H2O2 production and consequent injury progressing to apoptosis were initiated in the sinusoidal endothelial cells (SECs). After SECs were injured, H2O2 appeared in the hepatocytes. H2O2 production and associated degenerative changes were attenuated both morphologically and enzymatically by the addition of RBCs, a specific xanthine oxidase (XOD) inhibitor and the H2O2 radical scavenger, catalase. Conclusions: In the liver perfused with RBC-free buffer, H2O2 production and consequent injury were initiated in SECs. RBCs attenuate liver injury by scavenging XOD-dependent H2O2. [source] The cytoprotective effects of addition of activated protein C into preservation solution on small-for-size grafts in ratsLIVER TRANSPLANTATION, Issue 1 2010Naohisa Kuriyama Small-for-size liver grafts are a serious obstacle for partial orthotopic liver transplantation. Activated protein C (APC), a potent anticoagulant serine protease, is known to have cell-protective properties due to its anti-inflammatory and antiapoptotic activities. This study was designed to examine the cytoprotective effects of a preservation solution containing APC on small-for-size liver grafts, with special attention paid to ischemia-reperfusion injury and shear stress in rats. APC exerted cytoprotective effects, as evidenced by (1) increased 7-day graft survival; (2) decreased initial portal pressure and improved hepatic microcirculation; (3) decreased levels of aminotransferase and improved histological features of hepatic ischemia-reperfusion injury; (4) suppressed infiltration of neutrophils and monocytes/macrophages; (5) reduced hepatic expression of tumor necrosis factor , and interleukin 6; (6) decreased serum levels of hyaluronic acid, which indicated attenuation of sinusoidal endothelial cell injury; (7) increased hepatic levels of nitric oxide via up-regulated hepatic endothelial nitric oxide synthesis expression together with down-regulated hepatic inducible nitric oxide synthase expression; (8) decreased hepatic levels of endothelin 1; and (9) reduced hepatocellular apoptosis by down-regulated caspase-8 and caspase-3 activities. These results suggest that a preservation solution containing APC is a potential novel and safe product for small-for-size liver transplantation, alleviating graft injury via anti-inflammatory and antiapoptotic effects and vasorelaxing conditions. Liver Transpl 16:1,11, 2010. © 2009 AASLD. [source] Dietary Steatotic Liver Attenuates Acetaminophen Hepatotoxicity in MiceMICROCIRCULATION, Issue 1 2006YOSHIYA ITO ABSTRACT Objective: To determine whether hepatic steatosis is susceptible to acetaminophen (APAP) hepatotoxicity. Methods: Male C57Bl/6 mice were fed a "Western-style" diet (high fat and high carbohydrate) for 4 months to develop severe hepatic steatosis with mild increases in alanine aminotransferase (ALT) levels. These were compared to mice fed a standard chow diet. Results: Treatment with APAP (300 mg/kg, orally) to mice fed a regular chow increased ALT levels (519-fold) and caused hepatic centrilobular injury at 6 h. APAP increased hepatic cytochrome-P (CYP)-2E1 mRNA levels (17-fold). In vivo microscopic studies showed that APAP caused a 30% decrease in sinusoidal perfusion and the infiltration of red blood cells into the space of Disse. Electron microscopy demonstrated that numerous gaps were formed in sinusoidal endothelial cells. Mice fed the "Western-style" diet were protected from APAP hepatotoxicity as evidenced by 89% decrease in ALT levels and less centrilobular injury, which was associated with 42% decrease in CYP2E1 mRNA levels. The APAP-induced liver microcirculatory dysfunction was minimized in mice fed the "Western-style" diet. Conclusions: These results suggest that hepatic steatosis elicited by the "Western-style" diet attenuated APAP-induced hepatotoxicity by inhibiting CYP2E1 induction and by minimizing sinusoidal endothelial cell injury, leading to protection of liver microcirculation. [source] | ||||||||||