Poly(ADP-ribose) polymerase triggers the microvascular mechanisms of hepatic ischemia-reperfusion injury

Abstract

(ADP-ribose) polymerase triggers the microvascular mechanisms of hepatic ischemia-reperfusion injury. Am J Physiol Gastrointest Liver Physiol 283: G553-G560, 2002. First published May 22, 2002 10.1152/ajpgi.00085.2002.-Activation of poly(ADP-ribose) polymerase (PARP) mediates oxidative stress-induced cell injury. We tested the hypothesis that PARP contributes to ischemia-reperfusion (I/R) damage of the liver by triggering the mechanisms of microcirculatory failure. Leukocyte-and platelet-endothelial cell interactions as well as sinusoidal perfusion were analyzed by intravital fluorescence microscopy after lobar hepatic I/R (90 min/30 min) in C57BL/6 ϫ 129/Sv wild-type (PARPϩ/ϩ) and PARP-deficient (PARPϪ/Ϫ) mice. Hepatic I/R induced leukocyte/platelet-endothelial cell interactions and tissue injury in PARPϩ/ϩ mice, as indicated by impaired sinusoidal perfusion and increased alanine aminotransferase (ALT)/aspartate aminotransferase (AST) serum activities. In PARPϪ/Ϫ mice, however, the postischemic increase in the numbers of rolling/adherent leukocytes and platelets was significantly lower. In addition, I/R-induced translocation of CD62P as well as mRNA expression of CD62E, CD54, and CD106 were attenuated. The degree of perfusion failure was reduced and the increase in the ALT/AST activities was lower in PARPϪ/Ϫ mice compared with PARPϩ/ϩ mice. We conclude that PARP contributes to hepatic microvascular injury by triggering the expression/translocation of adhesion molecules and modulating leukocyte/platelet-endothelial cell interactions.

Ultrafine Particles Exert Prothrombotic but Not Inflammatory Effects on the Hepatic Microcirculation in Healthy Mice In Vivo

“…Therefore, the character of UFP-induced platelet-endothelial cell interactions seems to be different from that of inflammation-associated interactions of platelets with the endothelium as observed in the postischemic liver in our previous investigations. 21,22,26 After hepatic ischemiareperfusion, in contrast to UFP exposure, platelet rolling precedes permanent adhesion, and platelet adhesion is not restricted to venules and sinusoids but rather is also observed in terminal arterioles. 20 Although UFPs were recently shown to enhance ADPinduced platelet activation, 14 we addressed the issue of whether platelet recruitment can be mediated by prothrombotic changes on the hepatic endothelium in response to the systemic infusion of particles.…”

“…Next, fluorescein isothiocyanate (FITC)-labeled dextran (MW 150 000; 0.1 mL, 5%, Sigma-Aldrich) was infused and liver acini were scanned using an I2/3 filter block (excitation, 450 to 490 nm; emission, Ͼ515 nm; Leitz) for assessment of sinusoidal perfusion and microvascular permeability. 20,21 Twenty minutes was required to complete intravital microscopy.…”

Investigation the effects of cilostazol and rosuvastatin on kidney and heart: An experimental acute kidney and heart injury model

“…Density and intensity of dye uptake of the TNF-a antibody was evaluated, as described by Khandoga et al [9] The TNF-a was evaluated as no staining (-), slight staining (+) and intense staining (++). Immunohistochemical findings according to the groups were calculated as 0 points for no staining (-), 1 point for slight staining (+) and 2 points for intense staining (++).…”

Protective Effect of Glutathione Against Liver Warm Ischemia‐Reperfusion Injury in Rats is Associated with Regulation of P‐Selectin and Neutrophil Infiltration

“…The peroxidase reaction was developed with 3,3-diaminobenzidine tetrahydro-chloride (Beijing Zhongshan Biotechnology Co. Ltd.). In each experimental group, 15 sections from each of 15 individual animals (10 observation fields per section) were examined by light microscopy, and CD62P expression was analyzed semiquantitatively in a blinded manner using a grading system of 0-2: 0, no staining; 1, weak staining; 2, strong staining (Khandoga et al, 2002).…”