rHuEPo Reduces Ischemia-Reperfusion Injury and Improves Survival After Transplantation of Fatty Livers in Rats

Schmeding, Maximilian; Rademacher, Sebastian; Boas-Knoop, Sabine; Roecken, Christoph; Lendeckel, Uwe; Neumann, Ulf

doi:10.1097/tp.0b013e3181c425fd

Cited by 20 publications

(17 citation statements)

References 43 publications

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“…Twenty-six of included 40 articles are observational studies [14,, while the remaining are interventional studies [7,8,[15][16][17][18][43][44][45][46][47][48][49][50][51]. Nine in vitro cell culture studies were reported using various cell lines.…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

“…The 31 included animal studies score ranging from 2 to 6 (see Table 2), and contained 4 studies ranked A [18,19,45,50], 23 ranked B [15][16][17]23,24,27,28,[30][31][32][33][34][35][36][37][38]43,44,[46][47][48][49]51], and 4 ranked C [26,29,39,42]. In subject classification, the study of intervention gets the highest marks, owing to better control of temperature and blinded assessment of outcome.…”

Section: Quality Assessment Of Included Studiesmentioning

confidence: 99%

“…In animal hypoxia models, oxygen concentration was varied from 0% to 21% (asphyxia, hypoxia, and normoxia) with time spans from acute hypoxia to tolerant hypoxia. In 21 IR animal models, 11 adopted 70% liver (left and middle lobe) IR (I: 1-6 h, R: 0.5-12 h) [15,16,23,24,36,37,39,43,46,47,51], 4 liver transplantation induced IR (I: 6-24 h, R: 2 h-14 d) [18,19,44,50] …”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

“…To our knowledge, there has not been a systematic review of the literature using similar criteria. Five [15][16][17][18][19] of these studies were suitable for meta-analysis.…”

Section: Literature Search and Selectionmentioning

confidence: 99%

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Systematic review with meta-analysis: HIF-1α attenuates liver ischemia–reperfusion injury

Guo

Zhou

et al. 2015

Transplantation Reviews

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Section: Characteristics Of Included Studiesmentioning

confidence: 99%

Section: Quality Assessment Of Included Studiesmentioning

confidence: 99%

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

“…To our knowledge, there has not been a systematic review of the literature using similar criteria. Five [15][16][17][18][19] of these studies were suitable for meta-analysis.…”

Section: Literature Search and Selectionmentioning

confidence: 99%

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Systematic review with meta-analysis: HIF-1α attenuates liver ischemia–reperfusion injury

Guo

Zhou

et al. 2015

Transplantation Reviews

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“…5,10 In stark contrast to our findings, hypoxia has been viewed by most as detrimental to liver regeneration, 28 and abrogating hypoxia through surgical maneuvers, like portal vein arterialization, has been considered beneficial to the regenerating liver. 25 Recently, investigators described the presence of the master regulator of hypoxia HIF-1a in regenerating livers after resection, 29,30 not just in response to hypoxic injury but as an important regulator of hepatic metabolism in general. 31,32 It also has been demonstrated that liver regeneration is actually increased in mice deficient for PHD-1 and that increased HIF-1a activity in the regenerating liver not only induced a protective response, but also accelerated liver regeneration.…”

Section: Article In Pressmentioning

confidence: 99%

Hypoxia of the growing liver accelerates regeneration

Schadde

Tsatsaris

Swiderska‐Syn

et al. 2017

Surgery

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Background. After portal vein ligation of 1 side of the liver, the other side regenerates at a slow rate. This slow growth may be accelerated to rapid growth by adding a transection between the 2 sides, i.e., performing portal vein ligation and parenchymal transection. We found that in patients undergoing portal vein ligation and parenchymal transection, portal vein hyperflow in the regenerating liver causes a significant reduction of arterial flow due to the hepatic arterial buffer response. We postulated that the reduction of arterial flow induces hypoxia in the regenerating liver and used a rat model to assess hypoxia and its impact on kinetic growth. Methods. A rat model of rapid (portal vein ligation and parenchymal transection) and slow regeneration (portal vein ligation) was established. Portal vein flow and pressure data were collected. Liver regeneration was assessed in rats using computed tomography, proliferation with Ki-67, and hypoxia with pimonidazole and HIF-1a staining. Results. The rat model confirmed acceleration of regeneration in portal vein ligation and parenchymal transection as well as the portal vein hyperflow seen in patients. Additionally, tissue hypoxia was observed after portal vein ligation and parenchymal transection, while little hypoxia staining was detected after portal vein ligation. To determine if hypoxia is a consequence or an inciting stimulus of rapid liver regeneration, we used a prolylhydroxylase blocker to activate hypoxia signaling pathways in the slow model. This clearly accelerated slow to rapid liver regeneration. Inversely, abrogation of hypoxia led to a blunting of rapid growth to slow growth. The topical application of prolyl-hydroxylase inhibitors on livers in rats induced spontaneous areas of regeneration. Conclusion. This study shows that pharmacologically induced hypoxic signaling accelerates liver regeneration similar to portal vein ligation and parenchymal transection. Hypoxia is likely an accelerator of liver regeneration. Also, prolyl-hydroxylase inhibitors may be used to enhance liver regeneration pharmaceutically. Background. After portal vein ligation of 1 side of the liver, the other side regenerates at a slow rate. This slow growth may be accelerated to rapid growth by adding a transection between the 2 sides, i.e., performing portal vein ligation and parenchymal transection. We found that in patients undergoing portal vein ligation and parenchymal transection, portal vein hyperflow in the regenerating liver causes a significant reduction of arterial flow due to the hepatic arterial buffer response. We postulated that the reduction of arterial flow induces hypoxia in the regenerating liver and used a rat model to assess hypoxia and its impact on kinetic growth. Methods. A rat model of rapid (portal vein ligation and parenchymal transection) and slow regeneration (portal vein ligation) was established. Portal vein flow and pressure data were collected. Liver regeneration was assessed in rats using computed tomography, proliferation with Ki-6...

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A novel synergistic effect of iron depletion on antiangiogenic cancer therapy

Ohara

Noma

Urano

et al. 2012

Intl Journal of Cancer

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Iron is an essential element for both normal and cancer cells in humans. Treatment to reduce iron levels has been shown to suppress tumor growth in vivo. However, iron depletion monotherapy by iron decreased treatment has not been thought to be superior to ordinary chemotherapy and is not part of the standard therapeutic strategy for the treatment of cancer. Iron depletion is also known to reduce serum hemoglobin and oxygen supply to the tissue, which indicates that iron depletion may induce angiogenesis. Therefore, we hypothesized that iron depletion with antiangiogenic therapy can have a novel therapeutic effect in the treatment of cancer. Human nonsmall cell carcinoma cell lines A549 and H1299 were used in our study. An iron-deficient diet and an iron chelator were used to simulate an iron-depleted condition. The antitumor effects of iron depletion and antiangiogenic therapy were determined on A549 xenograft mice. The iron-depleted condition produced by an iron-deficient diet suppressed tumor growth. Tumor tissue from the iron-deficient diet group showed that cancer cell proliferation was suppressed and hypoxia was induced. Microvessel density of this group was increased which suggested that the iron-depleted condition induced angiogenesis. Bevacizumab administration had a synergetic effect on inhibiting the tumor growth on Day 39. An iron-depleted condition inhibited cancer cell proliferation and reciprocally induced angiogenesis. Bevacizumab synergistically enhanced the iron-depleted antitumor effect. Treatment to deplete iron levels combined with anti-angiogenic therapy could induce a novel therapeutic effect in the treatment of cancer.

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rHuEPo Reduces Ischemia-Reperfusion Injury and Improves Survival After Transplantation of Fatty Livers in Rats

Abstract: Erythropoietin improves marginal graft function and recipient survival after transplantation of fatty livers in rats.

Cited by 20 publications

References 43 publications

Systematic review with meta-analysis: HIF-1α attenuates liver ischemia–reperfusion injury

Systematic review with meta-analysis: HIF-1α attenuates liver ischemia–reperfusion injury

Hypoxia of the growing liver accelerates regeneration

A novel synergistic effect of iron depletion on antiangiogenic cancer therapy

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