Storage solution containing fructose-1,6-bisphosphate inhibits the excess activation of kupffer cells in cold liver preservation1.

Hirokawa, Fumitoshi; Nakai, Takehiro; Yamaue, Hiroki

doi:10.1097/00007890-200209270-00008

Cited by 22 publications

(17 citation statements)

References 27 publications

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“…It is thought that initial stimulation of Kupffer cells leads to enhanced phagocytosis with minimal secretory activity, whereas continued stimulation (e.g., prolonged cold preservation/reperfusion) increases the release of free radicals, cytokines, and other inflammatory mediators (21). The release of toxic mediators from activated Kupffer cells is a well-described early event in the hepatocellular damage and microcirculatory failure that occurs after cold or warm I/R (2,24,26,37).…”

Section: Discussionmentioning

confidence: 99%

Natural resistance to liver cold ischemia-reperfusion injury associated with the hibernation phenotype

Lindell¹,

Klahn²,

Piazza³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

116

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. Natural resistance to liver cold ischemia-reperfusion injury associated with the hibernation phenotype. Am J Physiol Gastrointest Liver Physiol 288: G473-G480, 2005; doi:10.1152/ajpgi.00223.2004.-The success of liver grafts is currently limited by the length of time organs are cold preserved before transplant. Novel insights to improve viability of cold-stored organs may emerge from studies with animals that naturally experience low body temperatures (T b) for extended periods. In this study, we tested whether livers from hibernating ground squirrels tolerate cold ischemia-warm reperfusion (cold I/R) for longer times and with better quality than livers from rats or summer squirrels. Hibernators were used when torpid (T b Ͻ 10°C) or aroused (Tb ϭ 37°C). Livers were stored at 4°C in University of Wisconsin solution for 0 -72 h and then reperfused with 37°C buffer in vitro. Lactate dehydrogenase (LDH) release after 60 min was increased 37-fold in rat livers after 72 h cold I/R but only 10-fold in summer livers and approximately three-to sixfold in torpid and aroused hibernator livers, despite twofold higher total LDH content in livers from hibernators compared with rats or summer squirrels. Reperfusion for up to 240 min had the least effect on LDH release in livers from hibernators and the greatest effect in rats. Compared with rats or summer squirrels, livers from hibernators after 72 h cold I/R showed better maintenance of mitochondrial respiration, bile production, and sinusoidal lining cell viability, as well as lower vascular resistance and Kupffer cell phagocytosis. These results demonstrate that the hibernation phenotype in ground squirrels confers superior resistance to liver cold I/R injury compared with rats and summer squirrels. Because hibernation-induced protection is not dependent on animals being in the torpid state, the mechanisms responsible for this effect may provide new strategies for liver preservation in humans. transplantation; cold storage; Kupffer cells; sinusoidal lining cells DESPITE MAJOR ADVANCES IN hypothermic preservation of organs before transplant, problems associated with extended cold ischemia-reperfusion (cold I/R) injury still limit the optimal use of transplantation as a therapeutic intervention for organ failure. For example, human livers can be successfully stored at 4°C for up to 12 h in University of Wisconsin (UW) solution, but graft failure is greatly increased after extended storage periods (14,33,34). In the rat liver transplant model, when livers are cold stored in UW for up to 24 h, 100% of the recipients survive (42); in contrast, without nutritional manipulation, none survive after receiving livers stored for 48 h (39).The damaging effects of cold I/R are evident on organ reperfusion with warmed, oxygenated blood, with damage increasing with the length of the cold ischemia period (10,35,40).A variety of pharmacological strategies has been explored to improve graft function after cold I/R to extend cold storage times and provide more flexibility in organ distribut...

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Section: Discussionmentioning

confidence: 99%

Natural resistance to liver cold ischemia-reperfusion injury associated with the hibernation phenotype

Lindell¹,

Klahn²,

Piazza³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

116

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“…Control group (n ϭ 6) received 4°C LRG solution, normothermic group (N-group, n ϭ 6) received 25°C LRG solution, normothermic oxygenated group (N-O group, n ϭ 6) received 25°C oxygenated LRG solution, normothermic FBP group (N-FBP group, n ϭ 6) received a 25°C LRG solution containing 10 mmol/L FBP, normothermic oxygenated FBP group (N-O-FBP group, n ϭ 6) received a 25°C oxygenated LRG solution containing 10 mmol/L FBP. Our preliminary reports clarified that the solution containing 10 mmol/L FBP showed cytoprotective and hepatotrophic effects of hepatocytes and inhibited excess activation of Kupffer cells function [15,16]. Then, we used 10 mmol/L FBP as an optimal dose and defined 25°C as a normothermic temperature.…”

Section: In Situ Evaluation Of Liver Metabolism and Energy Levelmentioning

confidence: 99%

“…Kupffer cells were separated from the rat liver by means of the collagenase perfusion method and metrizamide gradient centrifuga- tion [15,16]. Laparotomy was performed under intraperitoneal anesthesia of pentobarbital.…”

Section: In Vitro Evaluation Of Kupffer Cell Functionmentioning

confidence: 99%

“…Fructose-1, 6-bisphosphate (FBP) is a substrate of the glycolytic pathway whose effects include activation of glycolysis, inhibition of glyconeogenesis, stimulation of phospholipid synthesis, activation of the reticuloendothelial system, and inhibition of the production of free radicals [12][13][14][15]. We have reported previously that intravenous administration of FBP enhanced the DNA synthesis rate, the protein synthesis rate and the labeling index of the liver [14].…”

Section: Introductionmentioning

confidence: 99%

“…These findings indicate that FBP has cytoprotective and hepatotrophic effects on livers with ischemic injury. Moreover, we also have reported that FBP strongly controlled the priming of Kupffer cells, compared with the University of Wisconsin solution [15], has a chelating action on Ca 2ϩ , and that the rise of intracellular Ca 2ϩ concentration was inhibited when the Kupffer cells were pretreated with FBP [16].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effect of Normothermic Perfusion Using Fructose-1,6-Bisphosphate for Maintenance of Liver Function During In Situ Extended Hepatectomy by the Total Hepatic Vascular Exclusion Technique

Uemura

Uchiyama

Ozawa

et al. 2007

Journal of Surgical Research

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Characterization of the high-affinity uptake of fructose-1,6-bisphosphate by cardiac myocytes

Wheeler

Chien

2012

Mol Cell Biochem

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Previously, we reported that fructose-1,6-bisphosphate (FBP) was taken up by rat cardiac myocytes by two processes: a component that was saturable at micromolar levels and a nonsaturable component that dominated at millimolar levels. Here, we continued to characterize the saturable high-affinity component, with the aim of identifying the physiological substrate and role for this activity. ATP, ADP, and AMP inhibited the uptake of FBP with apparent affinities of 0.2-0.5 mM. Fumarate and succinate were very weak inhibitors. Several phosphorylated sugars (ribulose-1,5-phosphate, fructose-1-phosphate, ribose-5-phosphate, and inositol-2-phosphate) inhibited FBP uptake with apparent affinities of 40-500 μM. As in our previous study, no tested compound appeared to bind as well as FBP. The data suggest that the best ligands have two phosphoryl groups separated by at least 8 Å. The rates of FBP uptake were measured from 3° to 37°. The calculated activation energy was 15-50 kJ/mol, similar to other membrane transport processes. Uptake of FBP was tested in several types of cells other than cardiac myocytes, and compared to the uptake of 2-deoxyglucose and L: -glucose. While FBP uptake in excess of that of L: -glucose was observed in some cells, in no case was the uptake as high as in cardiac myocytes. The physiological substrate and role for the high-affinity FBP uptake activity remain unknown.

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Storage solution containing fructose-1,6-bisphosphate inhibits the excess activation of kupffer cells in cold liver preservation1.

Abstract: The storage solution containing FBP controlled the secretion of cytokines and NO from Kupffer cells and maintained phagocytic ability. This solution was considered to be more useful than UW solution for Kupffer cell protection.

Cited by 22 publications

References 27 publications

Natural resistance to liver cold ischemia-reperfusion injury associated with the hibernation phenotype

Natural resistance to liver cold ischemia-reperfusion injury associated with the hibernation phenotype

Effect of Normothermic Perfusion Using Fructose-1,6-Bisphosphate for Maintenance of Liver Function During In Situ Extended Hepatectomy by the Total Hepatic Vascular Exclusion Technique

Characterization of the high-affinity uptake of fructose-1,6-bisphosphate by cardiac myocytes

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