Remote Liver Injury is Attenuated by Adenovirus‐Mediated Gene Transfer of Heme Oxygenase‐1 During the Systemic Inflammatory Response Syndrome

McCarter, Sarah D.; Badhwar, Amit; Scott, Jeffrey R.; Akyea, Thelma; Bihari, Aurelia; Dungey, Alison A.; Harris, Kenneth A.; Potter, Richard F.

doi:10.1080/10739680490503384

Cited by 16 publications

(10 citation statements)

References 48 publications

(66 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with this study, some investigators detected microvascular perfusion deficits following limb I/R [44]. Other investigators attributed damaged hepatocytes to the microvascular reorganization of hepatic parenchyma [45].…”

Section: Discussionsupporting

confidence: 74%

The possible protective effect of exercise on liver damage following hind-limb ischemia–reperfusion injury in the adult male albino rat

Mohamed¹

2014

The Egyptian Journal of Histology

View full text Add to dashboard Cite

BackgroundHind-limb ischemia-reperfusion (I/R) injury is not limited to the lower extremities; it also causes damage to remote organs. Aim of the work This study was undertaken to investigate the role of exercise in attenuating remote hepatic damage following hind-limb I/R injury. Materials and methodsForty-five adult male rats were divided into three groups: the control group, the I/R group, and the exercise+I/R group. The rats were left to swim for 1 h, five times a week, for 4 weeks before I/R. Bilateral hind-limb ischemia was induced by application of rubber bands above the greater trochanter for 3 h. Blood samples were taken after 3 h of reperfusion for determination of malondialdehyde, superoxide dismutase, tumor necrosis factor-α, and interleukin-6. Liver specimens were processed for light and electron microscopic study. ResultsIn the I/R group, the superoxide dismutase level decreased and plasma levels of malondialdehyde, tumor necrosis factor-α, and interleukin-6 significantly increased when compared with the control group. Light microscopic examination showed hepatocytes with vacuolated cytoplasm, dilated blood sinusoids, and portal vessels. An extensive amount of collagen fibers around portal tracts and intense immune reaction for caspase-3 were observed. The ultrastructure showed hepatocytes with swollen mitochondria and disrupted cristae and others with an electron-dense matrix. Kupffer cells showed apoptotic bodies. Ito cells appeared surrounded by wide areas of collagen fibers. The exercise+I/R group showed significant attenuation of the biochemical and histological alterations of I/R-induced liver injury. ConclusionExercise could attenuate remote liver damage following hind-limb I/R injury.

show abstract

Section: Discussionsupporting

confidence: 74%

The possible protective effect of exercise on liver damage following hind-limb ischemia–reperfusion injury in the adult male albino rat

Mohamed¹

2014

The Egyptian Journal of Histology

View full text Add to dashboard Cite

show abstract

“…In regard to the above, several studies (27,28,32,42) have demonstrated beneficial anti-inflammatory effects of CO in preventing microvascular perfusion deficits and cellular injury Fig. 7.…”

Section: Discussionmentioning

confidence: 97%

CORM-3-derived CO modulates polymorphonuclear leukocyte migration across the vascular endothelium by reducing levels of cell surface-bound elastase

Mizuguchi

Stephen²,

Bihari³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Recently, it has been shown that carbon monoxide (CO)-releasing molecule (CORM)-released CO can suppress inflammation. In this study, we assessed the effects and potential mechanisms of a ruthenium-based water-soluble CO carrier [tricarbonylchloroglycinate-ruthenium(II) (CORM-3)] in the modulation of polymorphonuclear leukocyte (PMN) inflammatory responses in an experimental model of sepsis. Sepsis in mice was induced by cecal ligation and puncture. CORM-3 (3 mg/kg iv) was administered 15 min after the induction of cecal ligation and puncture. PMN accumulation in the lung (myeloperoxidase assay), bronchoalveolar lavage (BAL) fluid, and lung vascular permeability (protein content in BAL fluid) were assessed 6 h later. In in vitro experiments, human PMNs were primed with LPS (10 ng/ml) and subsequently stimulated with formyl-methionyl-leucylphenylalanine (fMLP; 100 nM). PMN production of ROS (L-012/dihydrorhodamine-123 oxidation), degranulation (release of elastase), and PMN rolling, adhesion, and migration to/across human umbilical vein endothelial cells (HUVECs) were assessed in the presence or absence of CORM-3 (1-100 muM). The obtained results indicated that systemically administered CORM-3 attenuates PMN accumulation and vascular permeability in the septic lung. Surprisingly, in in vitro experiments, treatment of PMNs with CORM-3 further augmented LPS/fMLP-induced ROS production and the release of elastase. The latter effects, however, were accompanied by an inability of PMNs to mobilize elastase to the cell surface (plasma membrane), an event required for efficient PMN transendothelial migration. The CORM-3-induced decrease in cell surface levels of elastase was followed by decreased PMN rolling/adhesion to HUVECs and complete prevention of PMN migration across HUVECs. In contrast, treatment of HUVECs with CORM-3 had no effect on PMN transendothelial migration. Taken together, these findings indicate that, in sepsis, CORM3-released CO, while further amplifying ROS production and degranulation of PMNs, concurrently reduces the levels of cell surface-bound elastase, which contributes to suppressed PMN transendothelial migration.

show abstract

“…Vice versa, HO inhibition, which is achieved with the use of chromium mesoporphyrin (CrMP), significantly reduces sinusoidal diameters and volumetric flow and causes significantly increased numbers of stationary leukocytes and microvascular perfusion deficits. This results in increased hepatocellular injury and hepatocyte death in models of remote hepatic injury and systemic SIRS (538,912).…”

Section: A Antioxidative Antiadhesive and Anti-inflammatory Approamentioning

confidence: 98%

The Hepatic Microcirculation: Mechanistic Contributions and Therapeutic Targets in Liver Injury and Repair

Vollmar

Menger²

2009

Physiological Reviews

426

368

View full text Add to dashboard Cite

The complex functions of the liver in biosynthesis, metabolism, clearance, and host defense are tightly dependent on an adequate microcirculation. To guarantee hepatic homeostasis, this requires not only a sufficient nutritive perfusion and oxygen supply, but also a balanced vasomotor control and an appropriate cell-cell communication. Deteriorations of the hepatic homeostasis, as observed in ischemia/reperfusion, cold preservation and transplantation, septic organ failure, and hepatic resection-induced hyperperfusion, are associated with a high morbidity and mortality. During the last two decades, experimental studies have demonstrated that microcirculatory disorders are determinants for organ failure in these disease states. Disorders include 1) a dysregulation of the vasomotor control with a deterioration of the endothelin-nitric oxide balance, an arterial and sinusoidal constriction, and a shutdown of the microcirculation as well as 2) an overwhelming inflammatory response with microvascular leukocyte accumulation, platelet adherence, and Kupffer cell activation. Within the sequelae of events, proinflammatory mediators, such as reactive oxygen species and tumor necrosis factor-alpha, are the key players, causing the microvascular dysfunction and perfusion failure. This review covers the morphological and functional characterization of the hepatic microcirculation, the mechanistic contributions in surgical disease states, and the therapeutic targets to attenuate tissue injury and organ dysfunction. It also indicates future directions to translate the knowledge achieved from experimental studies into clinical practice. By this, the use of the recently introduced techniques to monitor the hepatic microcirculation in humans, such as near-infrared spectroscopy or orthogonal polarized spectral imaging, may allow an early initiation of treatment, which should benefit the final outcome of these critically ill patients.

show abstract

Remote Liver Injury is Attenuated by Adenovirus‐Mediated Gene Transfer of Heme Oxygenase‐1 During the Systemic Inflammatory Response Syndrome

Abstract: These data indicate that gene transfer of inducible HO is an effective method to protect the liver during SIRS, providing incentive for further investigation into gene therapy strategies exploiting this anti-inflammatory enzyme.

Cited by 16 publications

References 48 publications

The possible protective effect of exercise on liver damage following hind-limb ischemia–reperfusion injury in the adult male albino rat

The possible protective effect of exercise on liver damage following hind-limb ischemia–reperfusion injury in the adult male albino rat

CORM-3-derived CO modulates polymorphonuclear leukocyte migration across the vascular endothelium by reducing levels of cell surface-bound elastase

The Hepatic Microcirculation: Mechanistic Contributions and Therapeutic Targets in Liver Injury and Repair

Contact Info

Product

Resources

About