Glutathione Protects the Rat Liver Against Reperfusion Injury After Prolonged Warm Ischemia

Schauer, Rolf; Gerbes, Alexander L.; Vonier, Daniel; Meißner, Herbert; Michl, Patrick; Leiderer, Rosmarie; Schildberg, F. W.; Meßmer, K.; Bilzer, Manfred

doi:10.1097/01.sla.0000110321.64275.95

Cited by 107 publications

(77 citation statements)

References 47 publications

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“…Formation of reactive oxygen species is an important step in the onset of I-R damage [5,6]. Reduced glutathione is known to be a potent radical scavenger and has shown the ability to reduce I-R damage in different models [29,30]. Increased radical scavenging capacity in HP with Celsior solution, as shown by total liver glutathione levels, was most pronounced after 24-h reperfusion but was already visible after 10-min reperfusion.…”

Section: Discussionmentioning

confidence: 99%

Hypothermic in situ perfusion of the porcine liver using Celsior or Ringer-lactate solution

Dinant

Roseboom

Levi

et al. 2008

Langenbecks Arch Surg

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Background Hypothermic perfusion (HP) of the liver is applied during total vascular exclusion (TVE) to reduce ischemic injury during liver resection. No studies have been performed comparing different perfusion solutions for HP. The aim of this experimental study was to compare Ringerlactate solution (RL) with Celsior solution (Cs) for HP in a pig model of 60-min TVE. Method Twenty pigs underwent 60-min TVE of the liver. Groups were TVE without HP (no-HP, n=9), TVE with HP using RL (n=6), and TVE with HP using Cs (n=5). Blood and liver tissue samples were taken before TVE and during 24-h reperfusion. Results In the no-HP group, plasma aspartate aminotransferase values were significantly increased during reperfusion (p<0.05), while liver tissue pO 2 levels (p< 0.01) were decreased when compared to the HP groups. After 24-h reperfusion, bile production and liver tissue glutathione content were significantly higher (p<0.05) in the Cs group (42.0±1.7 mL/h and 44.9±2.2 nmol/mg, respectively) as compared to the RL group (31.5±3.5 mL/h and 19.6±1.8 nmol/mg, respectively). ConclusionThe protective effect of HP during TVE was confirmed in this study. HP with Cs was more effective in reducing ischemic injury as compared to HP with RL.

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Section: Discussionmentioning

confidence: 99%

Hypothermic in situ perfusion of the porcine liver using Celsior or Ringer-lactate solution

Dinant

Roseboom

Levi

et al. 2008

Langenbecks Arch Surg

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“…The slightly increased hepatic glutathione levels at noon were consistent with rats just ending a feeding period. Hepatic glutathione levels reflect the oxidative state of the liver and capacity to respond to injury (Schauer et al, 2004). Hepatic glutathione levels did not correlate with serum ALT levels or with specific genes.…”

Section: Rna Isolationmentioning

confidence: 99%

Variation in the Hepatic Gene Expression in Individual Male Fischer Rats

et al. 2005

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A new tool beginning to have wider application in toxicology studies is transcript profiling using microarrays. Microarrays provide an opportunity to directly compare transcript populations in the tissues of chemical-exposed and unexposed animals. While several studies have addressed variation between microarray platforms and between different laboratories, much less effort has been directed toward individual animal differences especially among control animals where RNA samples are usually pooled. Estimation of the variation in gene expression in tissues from untreated animals is essential for the recognition and interpretation of subtle changes associated with chemical exposure. In this study hepatic gene expression as well as standard toxicological parameters were evaluated in 24 rats receiving vehicle only in 2 independent experiments. Unsupervised clustering demonstrated some individual variation but supervised clustering suggested that differentially expressed genes were generally random. The level of hepatic gene expression under carefully controlled study conditions is less than 1.5-fold for most genes. The impact of individual animal variability on microarray data can be minimized through experimental design.

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“…24,25 Similarly, intravenous administration of GSH also protects hepatocytes from I/R injury and improves animal survival. 26 In our study, hepatic I/R injury resulted in a significant increase in tissue MPO activity (an index of neutrophil infiltration), a decrease in tissue levels of SOD, CAT and GSH (indices of antioxidant capacities), and an increase in the plasma level of MDA (an index of lipid peroxidation). However, SPA0355 treatment dramatically reversed these changes, indicating that SPA0355 protected hepatocytes by reducing the oxidative stress caused by I/R injury.…”

Section: Spa0355 Suppresses Oxidative Stressmentioning

confidence: 95%

SPA0355 Attenuates Ischemia/Reperfusion-Induced Liver Injury in Mice.

et al. 2014

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Hepatic ischemia/reperfusion (I/R) injury leads to oxidative stress and acute inflammatory responses that cause liver damage and have a considerable impact on the postoperative outcome. Much research has been performed to develop possible protective techniques. We aimed to investigate the efficacy of SPA0355, a synthetic thiourea analog, in an animal model of hepatic I/R injury. Male C57BL/6 mice underwent normothermic partial liver ischemia for 45 min followed by varying periods of reperfusion. The animals were divided into three groups: sham operated, I/R and SPA0355 pretreated. Pretreatment with SPA0355 protected against hepatic I/R injury, as indicated by the decreased levels of serum aminotransferase and reduced parenchymal necrosis and apoptosis. Liver synthetic function was also restored by SPA0355 as reflected by the prolonged prothrombin time. To gain insight into the mechanism involved in this protection, we measured the activity of nuclear factor-jB (NF-jB), which revealed that SPA0355 suppressed the nuclear translocation and DNA binding of NF-jB subunits. Concomitantly, the expression of NF-jB target genes such as IL-1b, IL-6, TNF-a and iNOS was significantly downregulated. Lastly, the liver antioxidant enzymes superoxide dismutase, catalase and glutathione were upregulated by SPA0355 treatment, which correlated with the reduction in serum malondialdehyde. Our results suggest that SPA0355 pretreatment prior to I/R injury could be an effective method to reduce liver damage.

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Glutathione Protects the Rat Liver Against Reperfusion Injury After Prolonged Warm Ischemia

Abstract: Intravenous GSH administration during reperfusion of ischemic livers prevents reperfusion injury in rats. Because GSH is well tolerable also in man, this novel approach could be introduced to human liver surgery.

Cited by 107 publications

References 47 publications

Hypothermic in situ perfusion of the porcine liver using Celsior or Ringer-lactate solution

Hypothermic in situ perfusion of the porcine liver using Celsior or Ringer-lactate solution

Variation in the Hepatic Gene Expression in Individual Male Fischer Rats

SPA0355 Attenuates Ischemia/Reperfusion-Induced Liver Injury in Mice.

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