raffinose and fructose-1-6-diphosphate

A safe and effective preservation solution is a precondition for liver transplantation, which is accepted as the radical treatment for patients with end-stage liver disease. The increasing use of marginal donors and non-heart beating donors as well as the establishment of a national organ allocation network call for better preservation. New preservation solutions like histidine-tryptophan-ketoglutarate (HTK) solution and Celsior solution have been introduced to liver preservation, and protective gene intervention and other modifications have also been investigated. In this article, we review recent advances in liver preservation solutions.. An English-language literature search was conducted using MEDLINE (1990-2005) on liver preservation solution, biliary complication, protective gene and other related subjects.. Although the high viscosity of the University of Wisconsin (UW) solution proved harmful to the hepatic microcirculation, three solutions showed equivalent preservation effects. When the cold ischemia time was short, there were no significant differences among the three solutions in the incidence of biliary complications. So far, modifications of preservation solutions have achieved great success. Several types of protective genes like A20, Bcl-2, Bcl-X(L) and HO-1 were reported to have definite liver protective effects. The addition of other substrates like TNF-alpha antibody, tacrolimus (FK506) and fructose-1,6-bisphosphate (FBP) can also improve the preservation effect. However, addition of insulin to UW solution is harmful to the graft.. In centers with highly-developed transplantation techniques, HTK and Celsior solutions are acceptable in liver preservation. Protective gene modification and addition of substrates like TNF-alpha antibody, FK506 and FBP are prominent approaches to improve liver preservation.

Topics: Adenosine; Allopurinol; Animals; Antibodies; Bile Duct Diseases; Disaccharides; Electrolytes; Fructosediphosphates; Glucose; Glutamates; Glutathione; Histidine; Humans; Insulin; Ischemia; Liver; Mannitol; Microcirculation; Organ Preservation Solutions; Potassium Chloride; Procaine; Raffinose; Tacrolimus; Transformation, Genetic; Tumor Necrosis Factor-alpha

Orthotopic liver transplantation (OLT) has been the standard treatment for end-stage acute and chronic liver disease. Ischemia-reperfusion (I/R) injury is one of the major causes of poor graft function early after OLT, and adversely influencing graft and patient survivals. It is unknown whether I/R injury influences liver fibrogenesis.. Livers from 25 adult male Wistar rats were randomly assigned into 5 experimental groups according to the preservation solution: saline solution (SS); University of Wisconsin (UW) solution; Fructose 1, 6-biphosphate (FBP); S-Nitroso-N-Acetylcysteine (SNAC): or UW+SNAC (SNAC+UW). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactic dehydrogenase (LDH) were determined in preservation solution samples at 2, 4, and 6 hours. After 6 hours of cold ischemia, ex situ reperfusion was applied to the liver for 15 minutes. Serum AST, ALT, LDH, and renin levels were determined. Fresh liver slices were processed for histological studies, determination of thiobarbituric acid reactive substances, catalase, and glutathione, and expression of TGF-β1 and angiotensin II AT1 receptor.. AST was significantly lower during cold storage with UW than with the older media (P=.001); ALT was lower in the FBP group (P=.023) and LDH was lower in the FBP and SNAC groups (P=.007). After reperfusion, serum AST, ALT, LDH, and TBARS showed no significant differences among the groups. Catalase was significantly lower in the SS and FBP groups (P=.008 and P=.006, respectively). Compared with UW, glutathione concentrations were significantly higher in SS, FBP, and SNAC 200 (P=.004). Renin levels were significantly lower in the FBP group (P=.022). No histological signs of preservation injury were observed in the hepatic sample. No expressions were detected of TGF-β1 or AT1 receptor.. In this experimental model of early reperfusion injury, preservation changes related to higher levels of renin, which suggest its role in fibrogenesis. FBP was associated with lower renin levels than other solutions including UW.

Topics: Acetylcysteine; Adenosine; Alanine Transaminase; Allopurinol; Animals; Aspartate Aminotransferases; Biomarkers; Catalase; Disease Models, Animal; Fructosediphosphates; Glutathione; Insulin; L-Lactate Dehydrogenase; Liver; Liver Cirrhosis; Liver Transplantation; Male; Organ Preservation Solutions; Raffinose; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Renin; Reperfusion Injury; Thiobarbituric Acid Reactive Substances; Time Factors; Transforming Growth Factor beta1

We assessed the effect of adding exogenous fructose-1,6-biphosphate (F16BP) to the preservation solution (University of Wisconsin storage solution) used during an experimental procedure of small bowel transplantation in rats.. We studied levels of the nucleotides hypoxanthine/xanthine and adenosine in tissue after cold ischemia, as well as histologic changes and associated deleterious processes such as bacterial translocation produced by the reperfusion associated with the transplantation.. The groups of rats treated with F16BP showed the lowest levels of hypoxanthine/xanthine and uric acid, the highest levels of adenosine, and the lowest levels of histologic damage and lactate dehydrogenase release to the bloodstream. Consumption of intestinal hypoxanthine during reperfusion was lowest in the groups treated with F16BP, as was the incidence of bacterial translocation.. This study shows a protective effect of exogenous F16BP added to University of Wisconsin solution during experimental intestinal transplantation in rats. This protective effect, reflected by decreased intestinal damage and bacterial translocation, was related to a decrease in adenosine triphosphate depletion during cold ischemia before intestinal transplantation, and to the reduced availability of xanthine oxidase substrates for free radical generation during reperfusion.

Topics: Adenosine; Adenosine Triphosphate; Allopurinol; Animals; Bacterial Translocation; Cryopreservation; Cytoprotection; Fructosediphosphates; Glutathione; Hypoxanthine; Insulin; Intestine, Small; Intestines; L-Lactate Dehydrogenase; Male; Organ Preservation Solutions; Oxidative Stress; Raffinose; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Uric Acid; Xanthine

Fructose-1,6-bisphosphate (FBP) has been reported to have a protective effect on liver injury following ischemic/reperfusion periods because it maintains ATP levels during cold preservation. In the present study, we evaluated the effects of addition of FBP to storage solutions for cold liver preservation during 12 or 36 hours. Adult male Wistar rats were randomly divided into three experimental groups. The hepatic perfusion and preservation were performed with these solutions: UW; UW plus 10 mmol/L FBP; and FBP 10 mmol/L (FBPS) alone. The biochemical measurements of AST and ALT were performed on samples of the cold storage solution after 12- or 36-hour preservation. UW and FBPS solutions showed similar preservation grades at 12 hours. Addition of 10 mmol/L of FBP to UW solution induced liver injury and a poor preservation grade during 12 or 36 hours. UW solution was better than FBPS after 36 hours preservation. UW solution continues to offer a superior performance for liver preservation during long times; however, FBPS may be an alternative for short cold preservation times.

Topics: Adenosine; Allopurinol; Animals; Fructosediphosphates; Glutathione; Insulin; Liver; Male; Models, Animal; Organ Preservation; Organ Preservation Solutions; Raffinose; Rats; Rats, Wistar

In liver transplantation, the activation of Kupffer cells at the time of cold preservation and reperfusion is considered to play an important role. In the present study, the usefulness of cold storage solution containing fructose-1,6-bisphosphate (FBP) was compared with University of Wisconsin (UW) solution in the function of Kupffer cells.. Kupffer cells were separated from rat liver stored at 4 degrees C in each storage solution. Four kinds of storage solutions were used: UW, simplified UW without FBP (0-FBP), and solutions with 10 or 20 mM FBP (10-FBP, 20-FBP). Lipopolysaccharide (LPS) labeled by fluorescein was loaded after 12 or 24 hr of cold preservation in each solution. The rates of cells uptaking LPS as phagocytic ability were measured using flow cytometry. Tumor necrosis factor-alpha, cytokine-induced neutrophil chemoattractant, and nitric oxide (NO) were measured in the supernatant.. Tumor necrosis factor-alpha values in the 20-FBP group were significantly lower than those in the UW group. Cytokine-induced neutrophil chemoattractant values at 60 min after loading LPS were significantly lower in the 20-FBP group than in the UW group. NO values at 24 hr after loading LPS were significantly lower in the 20-FBP group compared with the UW group. The 20-FBP group was highest in the rates of cells uptaking LPS after 24-hr cold preservation.. 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.

Topics: Adenosine; Allopurinol; Animals; Calcium; Chemotaxis, Leukocyte; Cold Temperature; Cytoprotection; Fructosediphosphates; Glutathione; Insulin; Kupffer Cells; Liver Transplantation; Male; Neutrophils; Nitric Oxide; Organ Preservation; Organ Preservation Solutions; Phagocytosis; Raffinose; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

The renal preservation ability of a flushing solution (F-M) with fructose-1,6-diphosphate (1 g/dl) and mannitol (2 g/dl) during cold ischaemia was studied with the isolated perfused rat kidney model and compared with the Euro-Collins (EC) and University of Wisconsin (UW) solutions. Kidneys were stored in hypothermia for 4 and 18 h after initial flushing with the solution being tested, and then reperfused at 37 degrees C in an isolated perfusion circuit for 90 min with a Krebs-Henseleit solution containing 4.5% albumin. Forty-four kidneys were studied and divided in a control group and six study groups according to the cold ischaemia time and flushing solution used. Renal functional parameters of plasma flow rate (PFR), renal vascular resistance (RVR), urine flow rate (UFR) glomerular filtration rate (GFR), fractional (FRNa) and net (TNa) sodium reabsortion were assessed during reperfusion. Conventional histology and malondialdehyde tissue levels (MDA) were also evaluated. Our results show that PFR, RVR, and UFR were similar in all study groups. After 4 and 18 h of cold ischaemia, GFR, FRNa and TNa were better, and conventional histology worse in F-M than in EC flushed kidneys. After 4 and 18 h of cold ischaemia, GFR, FRNa and TNa, in fact, were not different between F-M and UW flushed kidneys. After 4 h of cold ischaemia, conventional histology was similar in F-M and UW flushed kidneys. Nevertheless, after 18 h of cold ischaemia, UW flushed kidneys showed worse histological parameters than F-M flushed kidneys. After 4 h of cold ischaemia, MDA was similar in kidneys flushed with three solutions. After 18 h of cold ischaemia MDA was higher in EC than in F-M or UW flushed kidneys. In summary, our newly developed cold storage solution shows promising results in renal preservation and its ability to preserve is at least as good as UW solution assessed in the isolated perfused rat kidney.

Topics: Adenosine; Allopurinol; Animals; Cold Temperature; Fructosediphosphates; Glutathione; Hypertonic Solutions; In Vitro Techniques; Insulin; Kidney; Male; Mannitol; Organ Preservation; Organ Preservation Solutions; Perfusion; Raffinose; Rats; Rats, Sprague-Dawley

Topics: Adenosine; Adenosine Triphosphate; Alanine Transaminase; Allopurinol; Animals; Aspartate Aminotransferases; Bile; Fructosediphosphates; Glutathione; Insulin; Liver; Male; Mannitol; Organ Preservation; Organ Preservation Solutions; Oxygen Consumption; Perfusion; Portal System; Raffinose; Rats; Rats, Sprague-Dawley; Solutions; Time Factors; Vascular Resistance