Oxidative stress, hepatocellular integrity, and hepatic function after initial reperfusion in human hepatic transplantation

Grezzana, Tomáz Jesus Maria; Corso, Carlos Otávio; Zanotelli, Maria Lúcia; Marroni, Cláudio Augusto; Brandão, Ajácio; Schlindwein, Eduardo; Leipnitz, Ian; Meine, M.H.; Fleck, Alfeu de Medeiros; Cassal, Alvaro; Hope, Lynn; Hoppen, Ricardo Antônio; Kiss, Guillermo; Gleisner, A; Cerski, Thadeu; Belló‐Klein, Adriane; Severo, Vitor Estevam; Innocenti, Claudia; Cantisani, Guido Pio Cracco

doi:10.1016/j.transproceed.2004.03.100

Cited by 6 publications

(5 citation statements)

References 8 publications

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“…This is in direct contrast to NMP, where γ-glutamylcysteine concentrations increase during perfusion and glutathione stores are able to be maintained. This is a clinically relevant finding given prior studies demonstrating an acute depletion of reduced glutathione stores following graft reperfusion in clinical liver transplantation studies [18,19]. Though no clinical reports of transplantation of steatotic human livers after SNMP exist, these grafts may suffer severe ischemic-reperfusion injury (IRI) at reperfusion and could potentially experience higher rates of early allograft dysfunction (EAD) or post-reperfusion syndrome (PRS) as a result of glutathione depletion.…”

Section: Discussionmentioning

confidence: 69%

Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion

et al. 2019

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There continues to be significant debate regarding the most effective mode of ex situ machine perfusion of livers for transplantation. Subnormothermic (SNMP) and normothermic machine perfusion (NMP) are two methods with different benefits. We examined the metabolomic profiles of discarded steatotic human livers during three hours of subnormothermic or normothermic machine perfusion. Steatotic livers regenerate higher stores of ATP during SNMP than NMP. However, there is a significant depletion of available glutathione during SNMP, likely due to an inability to overcome the high energy threshold needed to synthesize glutathione. This highlights the increased oxidative stress apparent in steatotic livers. Rescue of discarded steatotic livers with machine perfusion may require the optimization of redox status through repletion or supplementation of reducing agents.

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Section: Discussionmentioning

confidence: 69%

Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion

et al. 2019

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“…Glutathione provides major protection in oxidative injury by participating in a cellular system of defense against oxidative damage. Several reports have indicated that tissue injury induced by various stimuli are coupled with glutathione depletion (18), and the maintenance of high levels of glutathione is essential to reduce oxidative stress during organ reoxygeneration (4,5,11). Therefore, the decrease in glutathione levels during I/R was probably due to its consumption during oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Beneficial effects of rutin andl-arginine coadministration in a rat model of liver ischemia-reperfusion injury

Acquaviva¹,

Lanteri²,

G³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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following liver ischemia results in oxidative stress leading to liver injury. The aim of this study was to investigate the combined effects of two antioxidant agents, rutin and L-arginine, in rat liver ischemia-reperfusion (I/R). Male Wistar rats were divided into five groups: 1) sham operated, 2) I/R, 3) I/R ϩ rutin, 4) I/R ϩ L-arginine, and 5) I/R ϩ rutin ϩ L-arginine. Plasmatic and hepatic levels of alanine transaminase (ALT), aspartate transaminase (AST), lipid peroxides (LOOH), and thiol groups (RSH) were examined, as well as DNA fragmentation and liver histopathology. Furthermore, to elucidate the pathophysiological processes involved in the antioxidant mechanism(s) of rutin and L-arginine, we assessed the expression of inducible (iNOS) and endothelial nitric oxide synthase (eNOS) isoforms and heme oxygenase-1 (HO-1), both playing key roles in the biochemical cascade of liver injury. Significant increase in plasmatic ALT and AST activities were observed in untreated I/R rats compared with sham-operated animals, whereas treatment with rutin or L-arginine in I/R rats reduced hepatic damage. Interestingly, combined therapy with rutin and Larginine resulted in a further reduction of plasmatic ALT and AST activities compared with rutin or L-arginine alone. These results were further confirmed by the analysis of DNA fragmentation, LOOH,

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“…26,27 Presumably, the overproduction of ROS and reactive nitrogen species during reperfusion is mainly mediated by activated Kupffer cells. ROS react with a great number of targets, including membrane lipids, proteins, DNA, and enzymes.…”

Section: Discussionmentioning

confidence: 99%

“…9,28 Their harmful effects are counterbalanced by efficient antioxidant mechanisms, including glutathione (GSH), which are essential for cell integrity. 27,29 Several experimental reports showed that GSH levels continuously decrease during cold storage, and the maintenance of high levels of GSH is essential to reduce oxidative stress during organ reoxygenation. Results in the present study confirm the role of oxidative stress in liver damage, induced by postischemic reperfusion.…”

Section: Discussionmentioning

confidence: 99%

Heme oxygenase 1 expression in postischemic reperfusion liver damage: effect of L‐Arginine

et al. 2006

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Ischemia/reperfusion (I/R) injury is a multifactorial process that affects liver function after transplantation and resectional surgery. Alterations in hepatic microcirculation and decreased hepatic flow can cause local hypoxia and consequently liver damage, which is worsened by reperfusion. The aim of this study was to evaluate if treatment with L-arginine improved hepatic function in rats with I/R injury. Animals were treated with L-arginine, ischemized for 30 min, and reperfused for 3 h. Plasmatic levels of GOT, GPT, lipid hydroperoxides (LOOH), and total thiol groups (RSH) were evaluated. In addition, we analyzed hepatic LOOH and RSH levels, DNA fragmentation, heme oxygenase 1 (HO-1) expression, and histological modifications. Our results demonstrate a significant improvement in hepatic function of I/R rats compared to the control group. Treatment with L-arginine increased the expression of HO-1. These data suggest that L-arginine could be useful in preventing oxidative damage during hepatic surgery.

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Oxidative stress, hepatocellular integrity, and hepatic function after initial reperfusion in human hepatic transplantation

Cited by 6 publications

References 8 publications

Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion

Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion

Beneficial effects of rutin andl-arginine coadministration in a rat model of liver ischemia-reperfusion injury

Heme oxygenase 1 expression in postischemic reperfusion liver damage: effect of L‐Arginine

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