New method of delivering gene-altered Kupffer cells to rat liver: Studies in an ischemia-reperfusion model

Froh, Matthias; Wheeler, Michael D.; Smutney, Olivia M; Zhong, Zhi; Bradford, Blair U.; Thurman, Ronald G.

doi:10.1053/gast.2003.50002

Cited by 12 publications

(10 citation statements)

References 31 publications

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“…rats pretreated with antioxidants. Our result is similar to that in a recent study by Froh et al (13), in which the injection of transducer Kupffer cells encoding the Cu/Zn-SOD gene significantly blunted the increase in the serum AST level and tissue injury in the liver subjected to ischemia-reperfusion injury.…”

Section: Discussionsupporting

confidence: 92%

Sympathetic vesicovascular reflex induced by acute urinary retention evokes proinflammatory and proapoptotic injury in rat liver

Hong¹,

Lin²,

Lee³

et al. 2005

American Journal of Physiology-Renal Physiology

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. Sympathetic vesicovascular reflex induced by acute urinary retention evokes proinflammatory and proapoptotic injury in rat liver. Am J Physiol Renal Physiol 288: F1005-F1014, 2005. First published December 21, 2004; doi:10.1152/ajprenal.00223.2004.-Increased hepatic sympathetic activity affects hepatic metabolism and hemodynamics and subsequently causes acute hepatic injury. We examined whether the vesicovascular reflex evoked by bladder overdistension could affect hepatic function, specifically reactive oxygen species (ROS)-induced inflammation and apoptosis, through activation of the hepatic sympathetic nerve. We evaluated the hepatic hemodynamics, hepatic sympathetic nervous activities, and cystometrograms in anesthetized rats subjected to acute urinary retention. We used a chemiluminescence method, an in situ nitro blue tetrazolium perfusion technique, and a DNA fragmentation/apoptosis-related protein assay to demonstrate de novo and colocalize superoxide production and apoptosis formation in rat liver. Acute urinary retention increased the hepatic sympathetic-dependent vesicovascular reflex, which caused hepatic vasoconstriction/hypoxia and increased superoxide anion production from the periportal Kupffer cells and hepatocytes, which were aggravated by the increase in volume and duration of urinary retention. The ROS-enhanced proinflammatory NF-B, activator protein-1, and ICAM-1 expression also promoted proapoptotic mechanisms, including increases in the Bax/Bcl-2 ratio, CPP32 expression, poly-(ADP-ribose)-polymerase cleavages, and DNA fragmentation and apoptotic cells in the liver. The proinflammatory and proapoptotic mechanisms were significantly attenuated in rats treated with hepatic sympathetic nerve denervation or catechin (antioxidant) supplement. In conclusion, our results suggest that acute urine retention enhances hepatic sympathetic activity, which causes hepatic vasoconstriction and evokes proinflammatory and proapoptotic oxidative injury in the rat liver. Reduction of the hepatic sympathetic tone or antioxidant supplement significantly attenuates these injuries. reactive oxygen species; apoptosis URINARY RETENTION OCCURS FREQUENTLY in patients with bladder outlet obstruction or neurogenic voiding dysfunction. Acute urinary retention (AUR) with a volume beyond physiological tolerance (overdistension) can become a physiological or pathological stressor, resulting in bladder injury (40). In addition, excessive stimulation of mechanical afferents in the overdistended urinary bladder could evoke a sympathetic nerve-mediated vesicovascular reflex, which could lead to vasoconstriction and functional impairment of the heart and kidney (7, 23) and, likely, in other visceral organs. Consequently, hypertension, tachycardia, and abnormal renal function are commonly seen in patients with AUR.Animal experiments have shown that increased hepatic sympathetic activity may cause hepatic injury through alterations of hepatic metabolism and hemodynamics (2,16,17,25,39) or through reactive oxygen species (ROS)-me...

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Section: Discussionsupporting

confidence: 92%

Sympathetic vesicovascular reflex induced by acute urinary retention evokes proinflammatory and proapoptotic injury in rat liver

Hong¹,

Lin²,

Lee³

et al. 2005

American Journal of Physiology-Renal Physiology

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“…Indeed, the ex-vivo gene modified BMM local infusion upregulated hepatic HO-1/LC3B expression and alleviated IRI in a mouse OLT model. This regimen makes Ad-related adverse effects negligible (51), while direct BMM infusion into the liver improves macrophage transfer efficacy as a cellular delivery system for HO-1 trafficking into the disease site (52). The present study using ex-vivo gene modified HO-1-overexpressing BMM in a clinically relevant mouse model is likely to validate and support future experiments in translational and clinical settings.…”

Section: Discussionmentioning

confidence: 99%

Heme oxygenase-1 regulates sirtuin-1–autophagy pathway in liver transplantation: From mouse to human

Nakamura

Kageyama

Shi

et al. 2018

American Journal of Transplantation

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Liver ischemia-reperfusion injury (IRI) represents a major risk factor of early graft dysfunction and a key obstacle to expanding the donor pool in orthotopic liver transplantation (OLT). Although graft autophagy is essential for resistance against hepatic IRI, its significance in clinical OLT remains unknown. Despite recent data identifying heme oxygenase-1 (HO-1) as a putative autophagy inducer, its role in OLT and interactions with sirtuin-1 (SIRT1), a key autophagy regulator, have not been studied. We aimed to examine HO-1-mediated autophagy induction in human OLT and in a murine OLT model with extended (20 hours) cold storage, as well as to analyze the requirement for SIRT1 in autophagy regulation by HO-1. Fifty-one hepatic biopsy specimens from OLT patients were collected under an institutional review board protocol 2 hours after portal reperfusion, followed by Western blot analyses. High HO-1 levels correlated with well-preserved hepatocellular function and enhanced SIRT1/LC3B expression. In mice, HO-1 overexpression by genetically modified HO-1 macrophage therapy was accompanied by decreased OLT damage and increased SIRT1/LC3B expression, whereas adjunctive inhibition of SIRT1 signaling diminished HO-1-mediated hepatoprotection and autophagy induction. Our translational study confirms the clinical relevance of HO-1 cytoprotection and identifies SIRT1-mediated autophagy pathway as a new essential regulator of HO-1 function in IR-stressed OLT.

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“…Narrowing of the sinusoidals is the consequence. Within minutes after reperfusion, enhanced levels of reactive oxygen species (ROS), such as superoxide (O 2 − ), hydrogen peroxide (H 2 O 2 ) and hydroxyl radical (OH • ), can be measured [8, 9, 11, 27]. Cellular sources for these ROS are mitochondrial metabolism, hepatocyte-derived xanthine oxidase, and KC- and SEC-associated NADPH oxidase [8, 9, 11, 28].…”

Section: Altered Redox Status and Reduced Microcirculatory Blood Flowmentioning

confidence: 99%

Ischemia/Reperfusion Injury in Liver Surgery and Transplantation: Pathophysiology

et al. 2012

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Liver ischemia/reperfusion (IR) injury is caused by a heavily toothed network of interactions of cells of the immune system, cytokine production, and reduced microcirculatory blood flow in the liver. These complex networks are further elaborated by multiple intracellular pathways activated by cytokines, chemokines, and danger-associated molecular patterns. Furthermore, intracellular ionic disturbances and especially mitochondrial disorders play an important role leading to apoptosis and necrosis of hepatocytes in IR injury. Overall, enhanced production of reactive oxygen species, found very early in IR injury, plays an important role in liver tissue damage at several points within these complex networks. Many contributors to IR injury are only incompletely understood so far. This paper tempts to give an overview of the different mechanisms involved in the formation of IR injury. Only by further elucidation of these complex mechanisms IR injury can be understood and possible therapeutic strategies can be improved or be developed.

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New method of delivering gene-altered Kupffer cells to rat liver: Studies in an ischemia-reperfusion model

Cited by 12 publications

References 31 publications

Sympathetic vesicovascular reflex induced by acute urinary retention evokes proinflammatory and proapoptotic injury in rat liver

Sympathetic vesicovascular reflex induced by acute urinary retention evokes proinflammatory and proapoptotic injury in rat liver

Heme oxygenase-1 regulates sirtuin-1–autophagy pathway in liver transplantation: From mouse to human

Ischemia/Reperfusion Injury in Liver Surgery and Transplantation: Pathophysiology

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