Relaxin as a Protective Substance in Preservation Solutions for Organ Transplantation, as Shown in an Isolated Perfused Rat Liver Model

Boehnert, Markus; Armbruster, Franz-Paul; Hilbig, Heidegard

doi:10.1016/j.transproceed.2008.03.038

Cited by 17 publications

(15 citation statements)

References 6 publications

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“…Our findings are in keeping with previous studies from our and other research groups showing that RLX exerts beneficial effects against organ ischaemic damage by reducing local leucocyte recruitment and oxidative stress 3,4. Accordingly, RLX has also been proposed as a protective substance in preservation solutions for lung and liver transplantation 5,35. Despite these intriguing data and the evidence that the kidney is the organ of greatest uptake of exogenously administered RLX 19, the specific signal transduction pathway by which RLX exerts its effects in the kidney remains to be fully elucidated.…”

Section: Discussionsupporting

confidence: 90%

Acute treatment with relaxin protects the kidney against ischaemia/reperfusion injury

Collino

Rogazzo

Pini

et al. 2013

J Cellular Molecular Medi

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Although recent preclinical and clinical studies have demonstrated that recombinant human relaxin (rhRLX) may have important therapeutic potential in acute heart failure and chronic kidney diseases, the effects of acute rhRLX administration against renal ischaemia/reperfusion (I/R) injury have never been investigated. Using a rat model of 1-hr bilateral renal artery occlusion followed by 6-hr reperfusion, we investigated the effects of rhRLX (5 μg/Kg i.v.) given both at the beginning and after 3 hrs of reperfusion. Acute rhRLX administration attenuated the functional renal injury (increase in serum urea and creatinine), glomerular dysfunction (decrease in creatinine clearance) and tubular dysfunction (increase in urinary excretion of N-acetyl-β-glucosaminidase) evoked by renal I/R. These beneficial effects were accompanied by a significant reduction in local lipid peroxidation, free radical-induced DNA damage and increase in the expression/activity of the endogenous antioxidant enzymes MnSOD and CuZnSOD superoxide dismutases (SOD). Furthermore, rhRLX administration attenuated the increase in leucocyte activation, as suggested by inhibition of myeloperoxidase activity, intercellular-adhesion-molecule-1 expression, interleukin (IL)-1β, IL-18 and tumour necrosis factor-α production as well as increase in IL-10 production. Interestingly, the reduced oxidative stress status and neutrophil activation here reported were associated with rhRLX-induced activation of endothelial nitric oxide synthase and up-regulation of inducible nitric oxide synthase, possibly secondary to activation of Akt and the extracellular signal-regulated protein kinase (ERK) 1/2, respectively. Thus, we report herein that rhRLX protects the kidney against I/R injury by a mechanism that involves changes in nitric oxide signalling pathway.

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Section: Discussionsupporting

confidence: 90%

Acute treatment with relaxin protects the kidney against ischaemia/reperfusion injury

Collino

Rogazzo

Pini

et al. 2013

J Cellular Molecular Medi

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“…Relaxin not only protects the myocardium from ischemia-reperfusion (IR) injury (see above) but also protects other tissues. Thus, there is protection from IR injury in rat liver (Boehnert et al, 2005(Boehnert et al, , 2008(Boehnert et al, , 2009) by attenuating oxidative stress, leukocyte activation, and improving oxygen supply. In kidney IR in rats, relaxin reduces renal apoptosis and TNF-a levels as well as creatinine and urea levels .…”

mentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides

Halls¹,

Bathgate²,

Sutton³

et al. 2015

Pharmacol Rev

118

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“…A total of 5 publications analyzing RLX potency in liver were identified. 3 publications by Boehnert et al evaluated the role of RLX in a perfused rat liver model [32][33][34]. In the first experimental model, University of Wisconsin (UW) solution was used for preservation and the reperfusion was performed with a hemoglobin free solution, additional doses of 32 ng/mL and 64 ng/mL of RLX were added, respectively.…”

Section: Liver Transplantation (Ltx)mentioning

confidence: 99%

“…Liver ischemia was induced for 3.5 h applying either 20 • C (warm) or 4 • C (cold) preservation conditions [34]. In the second experimental model, liver ischemia was induced for 5 h, and instead of UW, the HTK solution was used with 64 ng/mL of RLX in the preservation solution [32,33]. The authors concluded that RLX had a protective effect against IRI, which was indicated by reduced levels of malondialdehyde (MDA) and myeloperoxidase (MPO) and by the increased scattered light intensity (indicates increased oxygen supply).…”

Section: Liver Transplantation (Ltx)mentioning

confidence: 99%

Relaxin Positively Influences Ischemia—Reperfusion Injury in Solid Organ Transplantation: A Comprehensive Review

Jakubauskiene

Jakubauskas

Leber

et al. 2020

IJMS

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In recent decades, solid organ transplantation (SOT) has increased the survival and quality of life for patients with end-stage organ failure by providing a potentially long-term treatment option. Although the availability of organs for transplantation has increased throughout the years, the demand greatly outweighs the supply. One possible solution for this problem is to extend the potential donor pool by using extended criteria donors. However, organs from such donors are more prone to ischemia reperfusion injury (IRI) resulting in higher rates of delayed graft function, acute and chronic graft rejection and worse overall SOT outcomes. This can be overcome by further investigating donor preconditioning strategies, graft perfusion and storage and by finding novel therapeutic agents that could reduce IRI. relaxin (RLX) is a peptide hormone with antifibrotic, antioxidant, anti-inflammatory and cytoprotective properties. The main research until now focused on heart failure; however, several preclinical studies showed its potentials for reducing IRI in SOT. The aim of this comprehensive review is to overview currently available literature on the possible role of RLX in reducing IRI and its positive impact on SOT.

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Relaxin as a Protective Substance in Preservation Solutions for Organ Transplantation, as Shown in an Isolated Perfused Rat Liver Model

Cited by 17 publications

References 6 publications

Acute treatment with relaxin protects the kidney against ischaemia/reperfusion injury

Acute treatment with relaxin protects the kidney against ischaemia/reperfusion injury

International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides

Relaxin Positively Influences Ischemia—Reperfusion Injury in Solid Organ Transplantation: A Comprehensive Review

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