Pretreatment of Small-for-Size Grafts<i>In Vivo</i>by<i>γ</i>-Aminobutyric Acid Receptor Regulation against Oxidative Stress-Induced Injury in Rat Split Orthotopic Liver Transplantation

Hori, Tomohide; Üemoto, Shinji; Walden, Lindsay B.; Chen, Feng; Baine, Ann-Marie T.; Hata, Toshiyuki; Nguyen, Justin H.

doi:10.1155/2013/149123

Cited by 8 publications

(7 citation statements)

References 57 publications

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“…The mechanisms of attenuated β‐catenin activation are unclear. Significant oxidant stress and markedly increased free radical production in SFSG may be one reason, as many studies have shown that hypoxia or I/R injury could downregulate Wnt/β‐catenin signaling . However, Funato et al.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanisms of attenuated β-catenin activation are unclear. Significant oxidant stress and markedly increased free radical production in SFSG 32,40,41 may be one reason, as many studies have shown that hypoxia or I/R injury could downregulate Wnt/β-catenin signaling. 19,35,42,43 However, Funato et al showed that treatment of cells with a low dose of reactive oxygen species (ROS) induces rapid stabilization of β-catenin and a concomitant increase in the expression of endogenous Wnt target genes.…”

Section: Figurementioning

confidence: 99%

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Wnt agonist stimulates liver regeneration after small‐for‐size liver transplantation in rats

et al. 2015

Hepatology Research

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Aim: Liver regeneration is inhibited in small-for-size grafts, which plays a role in the failure of partial liver grafts after transplantation. The Wnt/β-catenin signaling pathway plays a critical role in liver development, regeneration and homeostasis. In this study, we investigated whether pharmacological activation of Wnt signaling improves liver regeneration after small-for-size liver transplantation. Tissue and blood samples were collected at various times after transplantation, and a survival study was performed. Methods:Results: Hepatic expression of active β-catenin and its downstream target gene Axin2 were decreased in 30% of liver grafts after transplantation while the Wnt agonist increased their expression similar to the 50% liver grafts. The Wnt agonist reversed inhibition of cyclin D1 expression and adenosine triphosphate production in the 30% liver grafts compared with the 50% grafts. The Wnt agonist also attenuated hepatocellular injury and increased the hepatocyte proliferation response, liver regeneration rate and survival after transplantation of the 30% liver graft.Conclusion: Activation of Wnt/β-catenin signaling in liver grafts by pharmacological pretreatment can accelerate regeneration in a partial liver transplant model.

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Section: Discussionmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Wnt agonist stimulates liver regeneration after small‐for‐size liver transplantation in rats

et al. 2015

Hepatology Research

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“…Oxidative stress and inflammatory reactions induced by the trauma caused by OLT are considered to be the main mechanisms for the formation of AKI resulting from ischemia and toxins ( 26 , 27 ). Ischemia-reperfusion injury, intestinal endotoxemia and the disruption of the internal environmental balance prompt the deterioration of AKI.…”

Section: Discussionmentioning

confidence: 99%

Ulinastatin ameliorates acute kidney injury following liver transplantation in rats and humans

Chi

et al. 2014

Experimental and Therapeutic Medicine

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Acute kidney injury (AKI) is a common complication following orthotopic liver transplantation (OLT) that evidently affects prognosis. However, no effective treatment exists for AKI. The aim of the present study was to elucidate whether ulinastatin application during OLT in humans can reduce kidney damage and improve renal function. In addition, the underlying mechanisms of ulinastatin were investigated on a rat autologous OLT (AOLT) model. In total, 60 patients undergoing an OLT were randomly selected to receive ulinastatin (U group; n=30) or saline (C group; n=30) during the OLT surgery. The patient demographics, AKI incidence rate, recovery indicators and renal injury indexes were measured during the perioperative period. In addition to the clinical trials, 40 rats were subjected to an AOLT and were divided into the control (C-R), sham-operation and ulinastatin treatment groups. Pathological renal damage, biomarkers of inflammation and oxidative stress were measured to investigate the effects and possible mechanisms of ulinastatin on AKI. In the clinical trials, ulinastatin application was shown to attenuate the incidence of AKI following OLT (P<0.05) and reduce the serum levels of cystatin C and urinary β2 microglobulin within 24 h of the OLT (P<0.05). Furthermore, ulinastatin was found to significantly improve the recovery of patients by reducing the time spent in the intensive care unit (P<0.01 vs. C group), the ventilation time and the hemodialysis rates (P<0.05 vs. C group). In the rat AOLT model, ulinastatin application was also shown to relieve renal pathological damage by reducing the serum cystatin C and creatinine levels. Notably, the levels of tumor necrosis factor-α, interleukin-6, hydrogen peroxide and reactive oxygen species were evidently reduced, while the level of superoxide dismutase was increased in the ulinastatin groups (P<0.05, vs. C-R group). In conclusion, ulinastatin application was demonstrated to protect against AKI following OLT by inhibiting inflammation and oxidation.

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“…In rat P-OLT, the most popular techniques for sealing the hepatic pedicles are (1) classic mass ligation/lobe ligation [34,54,60], (2) vessel-oriented/-piercing suturing [64], and (3) hemostatic MicroClips [38,65,66]. Scarce evidence can be found on the use of alternative, modified resection protocols in rat P-OLT [67,68].…”

Section: Technical Issues Concerning P-olt In Ratsmentioning

confidence: 99%

“…However, a second graft washout with saline or Ringer solution immediately before implantation - as used by some authors [66] - is not indispensable; it might prevent deleterious hyperkalemia following liver reperfusion [91]. Rinsing the liver graft in solutions at room or body temperature right before implantation, as applied by others [50,51,52], also could exert a positive effect on microvascular reperfusion [92,93], even though it might at the same time increase warm ischemia [92].…”

Section: Technical Issues Concerning P-olt In Ratsmentioning

confidence: 99%

Improving Research Practice in Rat Orthotopic and Partial Orthotopic Liver Transplantation: A Review, Recommendation, and Publication Guide

Czigány

Iwasaki²,

Yagi³

et al. 2015

Eur Surg Res

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Background: Due to a worldwide shortage of donor organs for liver transplantation, alternative approaches, such as split and living donor liver transplantations, were introduced to increase the donor pool and reduce mortality on liver transplant waiting lists. Numerous details concerning the mechanisms and pathophysiology of liver regeneration, small-for-size syndrome, rejection, and tolerance in partial liver transplantation facilitated the development of various animal models. The high number of preclinical animal studies contributed enormously to our understanding of many clinical aspects of living donor and partial liver transplantations. Summary: Microsurgical rat models of partial orthotopic liver transplantation are well established and widely used. Nevertheless, several issues regarding this procedure are controversial, not clarified, or not yet properly standardized (graft rearterialization, size reduction techniques, etc.). The major aim of this literature review is to give the reader a current overview of rat orthotopic liver transplantation models with a special focus on partial liver transplantation. The aspects of model evolution, microsurgical training, and different technical problems are analyzed and discussed in detail. Our further aim in this paper is to elaborate a detailed publication guide in order to improve the quality of reporting in the field of rat liver transplantation according to the ARRIVE guidelines and the 3R principle. Key Messages: Partial orthotopic liver transplantation in rats is an indispensable, reliable, and cost-efficient model for transplantation research. A certain consensus on different technical issues and a significant improvement in scientific reporting are essential to improve transparency and comparability in this field as well as to foster refinement.

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Pretreatment of Small-for-Size GraftsIn Vivobyγ-Aminobutyric Acid Receptor Regulation against Oxidative Stress-Induced Injury in Rat Split Orthotopic Liver Transplantation

Cited by 8 publications

References 57 publications

Wnt agonist stimulates liver regeneration after small‐for‐size liver transplantation in rats

Wnt agonist stimulates liver regeneration after small‐for‐size liver transplantation in rats

Ulinastatin ameliorates acute kidney injury following liver transplantation in rats and humans

Improving Research Practice in Rat Orthotopic and Partial Orthotopic Liver Transplantation: A Review, Recommendation, and Publication Guide

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