Xanthine Oxidoreductase and Preservation Injury in Human Liver Transplantation

Martí, Ramón; Murio, E.; Varela, Encarna; Bilbao, Itxarone; Pascual, C; Margarit, C; Segura, Ramón

doi:10.1097/01.tp.0000120384.52033.bc

Cited by 9 publications

(7 citation statements)

References 20 publications

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“…The results of the present study showed that, in stable maintenance hemodialysis patients, plasma XOR activity was significantly and independently associated with serum uric acid levels, and alanine transaminase; both of which are well known markers of elevated XOR 4 , 5 , 18 . Liver is the main sources of serum XO and hepatic damage caused by a variety of toxic agents has been reported to be associated with elevated serum XOR levels 4 .…”

Section: Discussionsupporting

confidence: 51%

Xanthine oxidoreductase activity is associated with serum uric acid and glycemic control in hemodialysis patients

Nakatani

Ishimura

et al. 2017

Sci Rep

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Xanthine oxidoreductase activity (XOR-a) plays an important role as a pivotal source of reactive oxygen species. In the present study, we investigated factors associated with plasma XOR-a in 163 hemodialysis patients (age 67.3 ± 10.9 years; 89 males and 74 females), using a newly established, highly-sensitive assay based on [13C2,15N2] xanthine and liquid chromatography/triple quadrupole mass spectrometry. Plasma glucose and serum uric acid levels correlated significantly and positively with plasma XOR-a. In multiple regression analyses, the presence of type 2 diabetes mellitus (T2DM) and plasma glucose were associated significantly, independently, and positively with plasma XOR-a. While serum uric acid correlated significantly and positively with plasma XOR-a in hemodialysis patients without T2DM, plasma glucose and serum glycated albumin, a new marker of glycemic control in diabetic hemodialysis patients, correlated significantly and positively with plasma XOR-a in those with T2DM. Multivariate analyses in those with T2DM revealed that plasma glucose and serum glycated albumin were associated significantly and independently with plasma XOR-a, and that serum uric acid was associated significantly and independently with XOR-a in those without T2DM. Our results suggested that glycemic control in hemodialysis patients may be important in regard to a decrease in ROS induced by XOR.

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Section: Discussionsupporting

confidence: 51%

Xanthine oxidoreductase activity is associated with serum uric acid and glycemic control in hemodialysis patients

Nakatani

Ishimura

et al. 2017

Sci Rep

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“…Therefore, predicting and estimating EAD is very important [ 35 ]. The clinical impact of effluent parameters on EAD has not been studied in detail [ 14 , 36 – 38 ]. In a review article, Bolondi et al suggested that the donor-risk index and extended criteria donor score cannot determine short-term graft and patient survival [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…These findings were confirmed in humans; higher effluent aminotransferase and LDH levels correlated with 1-month survival in liver transplant recipients [ 12 , 13 ]. Likewise, levels of xanthine oxidoreductase, pro-inflammatory cytokines, hyaluronic acid, von Willebrand factor, and other immune responses in caval effluent correlated with early graft dysfunction (EAD) [ 14 – 18 ].…”

Section: Introductionmentioning

confidence: 99%

Association of Graft Effluent Parameters with Donor Body Mass Index, Graft Quality, and Post-Transplant Events

et al. 2018

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BackgroundWe evaluated whether effluent parameters prior to reperfusion correlate with post-transplant outcomes in liver transplant recipients.Material/MethodsConcentrations of high mobility group box 1 protein (HMGB1), uncleaved cytokeratin-18 (M65), caspase-cleaved cytokeratin 18 fragment (M30), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP) were measured in effluent samples from 53 adult liver recipients (42 survived for 1 year and 11 did not survive).ResultsEffluent concentrations of ALP (p=0.006), AST (p=0.050), and Ca++ (p=0.003) were higher in patients with bacteriemia in the first post-transplant year and ALP (p=0.015) was higher in patients with early graft dysfunction (EAD). Multivariate analysis of effluent parameters showed that Ca++ >0.30 mmol/l (p=0.012, odds ratio [OR]=7.12, confidence interval [CI]=1.56–32.58), and ALP ≥27 IU/l (p=0.033, OR=5.31, CI=1.14–27.74) were significantly associated with 1-year post-transplant bacteriemia, whereas ALP ≥27 IU/l (p=0.020, OR=5.56, CI=1.32–23.46) was significantly associated with EAD. HMGB1 >54 pg/ml (p=0.008, OR=6.05, CI=1.59–23.00) was significantly associated with the donor body mass index (p=0.008, OR=6.05, CI=1.59–23.00) and fatty liver (p=0.005, OR=11.68, CI=2.10–64.01).ConclusionsEffluent parameters are indicators of liver quality and predict the outcome of liver transplantation. High effluent Ca++ and ALP are risk factors of post-transplant bacteriemia. In addition, high ALP is a risk factor of EAD, and high HMGB1 is an indicator of liver quality.

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“…Lipid peroxidation products, such as malondialdehyde and hydroxynonenal[ 13 , 36 , 54 - 56 ] have been widely used as a biomarkers of oxidative stress in IRI. The accelerated ROS production in post-ischemic tissues has been attributed to enzymes capable of reducing molecular oxygen and forming superoxide: xantine oxidase[ 57 - 59 ], NADPH oxidase[ 60 ] and nitric oxide synthase[ 11 ]. The contribution of each of these enzymes in IRI is assessed in the excellent review by Granger and Kvietys[ 28 ].…”

Section: The Role Of Oxidative Stress In Irimentioning

confidence: 99%

“…The contribution of each of these enzymes in IRI is assessed in the excellent review by Granger and Kvietys[ 28 ]. All this indicates that radicals can be formed from different sources, and consequently several protective strategies to decrease liver IRI have targeted different sources of ROS: xanthine oxidase (using allopurinol[ 59 , 61 ]) or NADPH oxidase[ 62 ], for example. Other strategies have included pharmacological interventions with antioxidants resulting in the neutralization of ROS effects[ 63 - 66 ].…”

Section: The Role Of Oxidative Stress In Irimentioning

confidence: 99%

Ubiquitin-proteasome system and oxidative stress in liver transplantation

Alva

Panisello‐Roselló

Flores

et al. 2018

WJG

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A major issue in organ transplantation is the development of a protocol that can preserve organs under optimal conditions. Damage to organs is commonly a consequence of flow deprivation and oxygen starvation following the restoration of blood flow and reoxygenation. This is known as ischemia-reperfusion injury (IRI): a complex multifactorial process that causes cell damage. While the oxygen deprivation due to ischemia depletes cell energy, subsequent tissue oxygenation due to reperfusion induces many cascades, from reactive oxygen species production to apoptosis initiation. Autophagy has also been identified in the pathogenesis of IRI, although such alterations and their subsequent functional significance are controversial. Moreover, proteasome activation may be a relevant pathophysiological mechanism. Different strategies have been adopted to limit IRI damage, including the supplementation of commercial preservation media with pharmacological agents or additives. In this review, we focus on novel strategies related to the ubiquitin proteasome system and oxidative stress inhibition, which have been used to minimize damage in liver transplantation.

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Xanthine Oxidoreductase and Preservation Injury in Human Liver Transplantation

Abstract: XOR release and neutrophil activation are produced during LT, and they are potentially injurious mechanisms associated with this therapy.

Cited by 9 publications

References 20 publications

Xanthine oxidoreductase activity is associated with serum uric acid and glycemic control in hemodialysis patients

Xanthine oxidoreductase activity is associated with serum uric acid and glycemic control in hemodialysis patients

Association of Graft Effluent Parameters with Donor Body Mass Index, Graft Quality, and Post-Transplant Events

Ubiquitin-proteasome system and oxidative stress in liver transplantation

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