Effect of erythropoietin on liver regeneration in an experimental model of partial hepatectomy

Gül, Mesut; Comert, Mustafa; Çakmak, Güldeniz Karadeniz; Kertiş, Gürkan; Ugurbas, Ebru; Öner, Muzaffer Önder

doi:10.1016/j.ijsu.2012.11.012

Cited by 17 publications

(11 citation statements)

References 27 publications

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“…There are various studies about the method and EPO dosage for use in animals, with some suggesting 3.000 UI of EPO/kg subcutaneously [1], 4.000 (UI of EPO/kg intraperitoneal [10]. This study showed that a dose of 200 UI EPO/kg subcutaneously, in spite of being considered a low dose, significantly reduced the regenerative ability of the remaining tissue after liver resection.…”

Section: Discussionmentioning

confidence: 81%

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The Use of Erythropoietin in Liver Regeneration in Pigs after Partial Hepatectomy

Wiederkehr¹,

Carvalho²,

Wiederkehr³

et al. 2015

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A partial hepatectomy is a surgical procedure performed during the living-donor liver transplantation and sometimes the only option for patients with hepatocarcinoma. However the remnant liver after the hepatectomy is still a major concern. Therefore, the process of liver regeneration has been a constant theme of study in order to optimize this process. Erythropoietin, a hormone produced by the kidney and involved in protecting organs like heart, liver and kidney itself against injuries can be one of these factors that could accelerate the liver regeneration. This study aims to observe if erythropoietin can accelerate the process of liver regeneration after partial hepatectomy in pigs. Methods: 8 pigs were classified into 2 groups of 4 pigs each: the control group and the test group. The animals in the first group underwent an application of saline solution subcutaneous on the day before the hepatectomy. Instead of saline solution, the test groups received a subcutaneous injection of 200 UI/lg of recombinant erythropoietin also on the day before the surgical procedure. After 7 days since the hepatectomy, in each animal the liver was biopsied in two regions, one next to the hepatectomy section and other far from it. The liver regeneration was analyzed using Ki-67. Results: Pigs from control group presented the following results: Control pig I: 30% of regeneration in the hepatectomy section and 10% in the region far from it; control pig II 24% and 4%; control pig III 27% and 7%. The test group presented no significant liver regenera-* Corresponding author. H. A. Wiederkehr et al. 519tion since Ki-67 could not identify cell proliferation in neither the biopsied areas. Conclusion: Since the number of pigs was not statistically significant, we could not conclude any further hypothesis. We strong believe that enhancing the number of pigs and testing different doses, we will be able to reach further conclusions.

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Section: Discussionmentioning

confidence: 81%

“…One of the distinctive and unique characteristics of the liver is its regenerative ability [1]. Partial hepatic resection is many times the only option for patients suffering with hepatocellular carcinoma and is a procedure frequently used in living-donor liver transplants.…”

Section: Introductionmentioning

confidence: 99%

The Use of Erythropoietin in Liver Regeneration in Pigs after Partial Hepatectomy

Wiederkehr¹,

Carvalho²,

Wiederkehr³

et al. 2015

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“…To our knowledge, the effect of EPO on hepatic tissue after renal I/R injury was not investigated before. However, the direct effect of EPO on hepatic tissue regeneration was previously investigated and showed that, systemic administration of highdose EPO increases hepatic tissue regeneration after liver resection and improved liver function and histopathology [20] . In addition, a reduction of hepatic apoptosis and necrosis was reported in EPO-treated graft livers [21,22] which might indicate a possible role for EPO in protection of the liver following renal I/R injury.…”

Section: Discussionmentioning

confidence: 99%

“…Gul and his team [20] demonstrated that, systemic administration of high-dose erythropoietin promotes regeneration of hepatic tissue by affecting biochemical and histopathological parameters after liver resection. Moreover, Schmeding et al, [21] reported an increase of regenerative capacity in EPO treated rats after major hepatectomy.…”

Section: Introductionmentioning

confidence: 99%

Potential Hepatic Protection by Erythropoietin and Ischemic Conditioning in a Rat Model of Renal Ischemia-Reperfusion Injury

Ibrahim¹,

Megahed

Fathy³

et al. 2018

The Medical Journal of Cairo University

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Background: Renal ischemia reperfusion injury is a common consequence of many clinical conditions including renal transplantation, sepsis, trauma, and shock and usually leads to acute kidney injury. Its adverse effects extend to other organs including the liver leading to remote organ injury. Erythropoietin and ischemic conditioning have an antiinflammatory, anti-oxidant and anti-apoptotic effects and were reported to have a protective effect against ischemia reperfusion injury in different organs. Aim of the Study:To evaluate the possible protective effect of erythropoietin and ischemic conditioning on the liver following renal ischemia reperfusion injury and to declare some of the possible mechanisms involved. Material and Methods:This study was conducted on 66 adult male albino rats divided into 6 equal groups: Group I: Sham group; Group II: Renal ischemia reperfusion group (I/R); Group III: Erythropoietin pre-treatment renal ischemia reperfusion group (EPO pre-I/R); Group IV: Erythropoietin post-treatment renal ischemia reperfusion group (EPO post-I/R); Group V: Ischemic pre-conditioning-renal ischemia reperfusion group (IPC) and Group VI: Ischemic postconditioning-renal ischemia reperfusion group (IPOC).Results: Group II showed significant increase in serum creatinine, blood urea, blood urea nitrogen, AST and ALT levels with significant increase in renal and hepatic injury score indicating renal and hepatic injury following renal ischemia reperfusion. In the same group, a significant increase in serum IL6, TNFa , MDA and a significant decrease in serum SOD were found. Both group III and IV revealed a significant decrease in serum creatinine, blood urea, blood urea nitrogen, AST, ALT, renal and hepatic injury score. Levels of IL6, TNFa , and MDA significantly decrease and SOD significantly increased in both groups relative to group II and these changes were significantly higher in group III relative to group IV. In group V and VI, a significant decrease in serum creatinine, blood urea, blood urea nitrogen and renal injury score was found in both groups, while serum AST, ALT and hepatic injury score were significantly decreased in group VI but remained insignificantly changed in group V versus group II. Serum IL6 and TNFa significantly decreased in both groups, while MDA significantly decreased and SOD significantly Correspondence to: Maha A. Fathy, Email: y_maha_m@hotmail.com increased in group VI only and no significant change was noticed in group V versus group II.Conclusion: Erythropoietin pre and post treatment significantly improved renal and hepatic function and morphology following renal ischemia reperfusion injury with better results for erythropoietin pre-treatment. Ischemic post-conditioning induced significant decrease in renal and hepatic injury, while ischemic pre-conditioning provided renal protective effect which didn't extend to involve the liver.

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“…EPO is a glycoprotein that promotes the proliferation and differentiation of erythrocyte precursors. It was reported that high-dose EPO increases liver regeneration by affecting the biochemical, morphological, and histopathological parameters after liver resection [58]. EPO increases brown fat gene expression [59].…”

Section: Liver Group Consists Of Epo Renin Sod Akr and Gshmentioning

confidence: 99%

The closed-loop pathways of signaling molecules

Liu

2017

Preprint

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The pathways of signaling molecules are important to understanding how signaling molecules regulate physiological function and also in predicting the pathological development which is important to therapeutic strategy, however the thorough knowledge of these pathways is still lack. In this paper, we used the big data concept to analyze the pathways of signaling molecules and categorize these molecules into five groups according to their origin and effect on the five organs of heart-spleen-lung-kidney-liver. Heart group includes IGF, Ang and Mg; spleen group includes ANP, aldosterone, retinoic acid and ghrelin; lung group includes FGF7, VEGF, ascorbic acid and HIF; kidney group includes calcitonin, PTHrP, Wnt and NO; and liver group includes EPO, renin, SOD, AKR and GSH.We found that each group of molecules have assisting effect on the other organ in the order of heart-spleen-lung-kidney-liver-heart, and have regulating effect on the other organ in the order of heart-lung-liver-spleen-kidney-heart. Moreover, the pathways of molecules of each group also follow these two arrangements, in which the pathways of molecules form a closed-loop that may lead to new therapeutic strategies.

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Effect of erythropoietin on liver regeneration in an experimental model of partial hepatectomy

Abstract: Our study showed that systemically administering high-dose EPO increases regeneration by affecting the biochemical, morphological, and histopathological parameters after liver resection.

Cited by 17 publications

References 27 publications

The Use of Erythropoietin in Liver Regeneration in Pigs after Partial Hepatectomy

The Use of Erythropoietin in Liver Regeneration in Pigs after Partial Hepatectomy

Potential Hepatic Protection by Erythropoietin and Ischemic Conditioning in a Rat Model of Renal Ischemia-Reperfusion Injury

The closed-loop pathways of signaling molecules

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