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Purpose: The anti-tumor activity of glucose analogs 2-deoxy-glucose (2-DG) and D-allose was investigated alone or in combination with p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190 or platinum analogs as a strategy to pharmacologically target glycolytic tumor phenotypes. Methods: Hypoxia inducible factor-1 alpha (HIF-1α) protein accumulation in pancreatic cell lines treated with SB202190 alone and in combination with glucose analogs was analyzed by Western blot. HIF-1α transcriptional activity was measured in MIA PaCa-2 cells stably transfected with a hypoxia response element luciferase reporter following treatment with glucose analogs alone, and in combination with SB202190. Induction of cleaved poly(ADP-ribose) polymerase (PARP) was measured by Western blot in the MIA PaCa-2 cells. In vitro anti-proliferative activity of 2-DG and D-allose alone, or in combination with oxaliplatin (pancreatic cell lines), cisplatin (ovarian cell lines), or with SB202190 were investigated using the MTT assay. Results: SB202190 decreased HIF-1α protein accumulation and transcriptional activity. 2-DG demonstrated greater anti-proliferative activity than D-allose. Pre-treatment with SB202190 enhanced activity of both 2-DG and D-allose in MIA PaCa-2, BxPC-3, ASPC-1, and SK-OV-3 cells. The combination of D-allose and platinum agents was additive to moderately synergistic in all but the OVCAR-3 and HEY cells. SB202190 pre-treatment further enhanced activity of D-allose and 2-DG with platinum agents in most cell lines investigated. Conclusions: SB202190 induced sensitization of tumor cells to 2-DG and D-allose may be partially mediated by inhibition of HIF-1α activity. Combining glucose analogs and p38 MAPK inhibitors with chemotherapy may be an effective approach to target glycolytic tumor phenotypes. [ABSTRACT FROM AUTHOR]

Background: Despite the implementation of various cancer therapies, adequate therapeutic efficacy has not been achieved. A growing number of studies have been dedicated to the discovery of new molecules to combat refractory cancer cells efficiently. Recently, the use of a rare type of sugar, D-allose, has attracted the attention of research communities. In combination with the first-line treatment of cancers, including different types of radiotherapies and chemotherapies, D-allose has been detected with favorable complementary effects. Understanding the mechanism of therapeutic target molecules will enable us to develop new strategies for cancer patients that do not currently respond to the present therapies., Objective: We aimed to provide a review of the effects of D-allose in cancer treatment, its mechanisms of action, and gaps in this field that require more investigations., Discussion: With rare exceptions, in many cancer types, including head and neck, lung, liver, bladder, blood, and breast, D-allose consistently has exhibited anticancer activity in vitro and/or in vivo. Most of the D-allose functions are mediated through thioredoxin-interacting protein molecules. D-allose exerts its effects via reactive oxygen species regulation, cell cycle arrest, metabolic reprogramming, autophagy, apoptosis induction, and sensitizing tumors to radiotherapy and chemotherapy., Conclusion: D-allose has shown great promise for combating tumor cells with no side effects, especially in combination with first-line drugs; however, its potential for cancer therapy has not been comprehensively investigated in vitro or in vivo., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

L-Rhamnose isomerase, an aldose-ketose isomerase, is an important enzyme for rare sugar production. In this paper, L-rhamnose isomerase (L-Rhl) from Bacillus subtilis 168 (B. subtilis L-Rhl) was cloned and expressed in Bacillus subtilis WB600 for the production of D-allose. The obtained crude L-Rhl was then purified through a HisTrap HP affinity chromatography column and an anion-exchange chromatography column. The characteristics of purified L-RhI were analyzed subsequently. The enzyme was activated in presence of Mn2+, and it had thermal advantages as its optimum temperature was 70°C, and 85% of its activity was retained after 4 hours' incubation at 60°C. In addition, isothermal titration calorimetry (ITC) was for the first time employed to determine the isomerization of rare sugars, and the kinetic data showed that B. subtilis L-Rhl had relatively low Km values on the substrates of L-rhamnose, L-mannose, D-ribose and D-allose. Using D-psicose as the substrate, no by-products but only D-allose was generated catalyzed by B. subtilis L-Rhl, and the yield of 37.51% was obtained when the reaction reached its equilibrium at 60°C. [ABSTRACT FROM AUTHOR]

Now a days sugar free food are very much popular because of their less calorie content. So food industry uses various artificial sweeteners which are low in calorie content instead of high calorie sugar. U.S. Food and Drug Administration has approved aspartame, acesulfame-k, neotame, cyclamate and alitame for use as per acceptable daily intake (ADI) value. But till date, breakdown products of these sweeteners have controversial health and metabolic effects. On the other hand, rare sugars are monosaccharides and have no known health effects because it does not metabolize in our body, but shows same sweet taste and bulk property as sugar. Rare sugars have no such ADI value and are mainly produced by using bioreactor and so inspite of high demand, rare sugars cannot be produced in the desired quantities. [ABSTRACT FROM AUTHOR]

The article presents a study that examines the anti-proliferative activites of 6-O-acyI-D-allose against the human leukemia MOLT-4F cell line. It describes the method of the study that observes the derivatives of the 6-O-acyI-D-allose which occurred in a furanose form. It also outlines the result of the study which indicates that 6-O-acyI-D-alloses have anti-proliferative effect on human leukemia MOLT-4F cells.

Only d-allose, among various rare monosaccharides tested, induced resistance to Xanthomonas oryzae pv. oryzae in susceptible rice leaves with defence responses: reactive oxygen species, lesion mimic formation, and PR-protein gene expression. These responses were suppressed by ascorbic acid or diphenylene iodonium. Transgenic rice plants overexpressing OsrbohC, encoding NADPH oxidase, were enhanced in sensitivity to d-allose. d-Allose-mediated defence responses were suppressed by the presence of a hexokinase inhibitor. 6-Deoxy-d-allose, a structural derivative of d-allose unable to be phosphorylated, did not confer resistance. Transgenic rice plants expressing Escherichia coli AlsK encoding d-allose kinase to increase d-allose 6-phosphate synthesis were more sensitive to d-allose, but E. coli AlsI encoding d-allose 6-phosphate isomerase expression to decrease d-allose 6-phosphate reduced sensitivity. A d-glucose 6-phosphate dehydrogenase-defective mutant was also less sensitive, and OsG6PDH1 complementation restored full sensitivity. These results reveal that a monosaccharide, d-allose, induces rice resistance to X. oryzae pv. oryzae by activating NADPH oxidase through the activity of d-glucose 6-phosphate dehydrogenase, initiated by hexokinase-mediated conversion of d-allose to d-allose 6-phosphate, and treatment with d-allose might prove to be useful for reducing disease development in rice. [ABSTRACT FROM AUTHOR]

Background: Recently, one of the rare sugars, D-allose, has received attention from many researchers because of its availability for mass production and its various physiological functions. Among these, an antioxidative effect has been strongly suggested. In this study, we investigated whether this effect is also applicable to the field of skin surgery. Methods: In ischemia-reperfusion injury model using the rat abdominal skin island flap (male Wistar rats, n = 110), D-allose was injected intravenously 15 min before 8-h ischemia. The survival area (%) was measured by digital photographic assessment 1 wk after surgery, and multiple comparisons (Fisher's protected least significant difference) were carried out. Histopathological examination (neutrophilic infiltration into dermis in hematoxylin and eosin stain) and immunostaining (of ectodermal dysplasia-1 (ED1)-positive cells/flap) were assessed. Myeloperoxidase (MPO) activity in the skin flap (sampling at the time of 8 h after reperfusion) was measured spectrophotometrically, and Student t-test was performed. Results: D-allose extended the survival of the remaining flaps, and a dose greater than 30 mg (0.1 mg/g) was necessary to be effective. The flap survival rates in the 30, 60, and 150 mg groups were significantly higher than that in the control (saline) group: 75.87 ± 5.90, 79.27 ± 7.81, and 77.87 ± 6.20 versus 50.53 ± 9.66, respectively (P < 0.05). ED1-positive cells/flap in 60 mg of D-allose and control (saline) were 78 ± 25.7 versus 124 ± 15.8, respectively (P = 0.08). The MPO activity in the D-allose 60 mg group was 0.40 ± 0.04, and that in the control (saline) was 0.72 ± 0.12. D-allose significantly reduced the skin tissue MPO activity (P < 0.05) compared with that in the control (saline) group. Conclusions: We proved that D-allose has a reducing effect against ischemia-reperfusion injury on the skin island flap model, and the mechanism is related to inhibiting the activity of neutrophils in the skin tissues. Compared with chemo-synthetic materials, rare sugars are safer for our bodies as well as the environment; therefore, this rare sugar project is expected to lead to the development of a safer antioxidant for skin flap surgery. [ABSTRACT FROM AUTHOR]

We previously reported that a rare sugar d-allose, which is the d-glucose epimer at C3, inhibits the gibberellin-dependent responses such as elongation of the second leaf sheath and induction of α-amylase in embryo-less half seeds in rice (Fukumoto et al. ). d-Allose suppresses expressions of gibberellin-responsive genes downstream of SLR1 protein in the gibberellin-signaling through hexokinase (HXK)-dependent pathway. In this study, we discovered that d-allose induced expression of ABA-related genes including OsNCED1- 3 and OsABA8ox1- 3 in rice. Interestingly, d-allose also up-regulated expression of OsABF1, encoding a conserved bZIP transcription factor in ABA signaling, in rice. The d-allose-induced expression of OsABF1 was diminished by a hexokinase inhibitor, d-mannoheptulose (MNH). Consistently, d-allose also inhibited Arabidopsis growth, but failed to trigger growth retardation in the glucose- insensitive2 ( gin2) mutant, which is a loss-of-function mutant of the glucose sensor AtHXK1. d-Allose activated AtABI5 expression in transgenic gin2 over-expressing wild-type AtHXK1 but not in gin2 over-expressing the catalytic mutant AtHXK1, indicating that the d-allose phosphorylation by HXK to d-allose 6-phosphate (A6P) is the first step for the up-regulation of AtABI5 gene expression as well as d-allose-induced growth inhibition. Moreover, overexpression of OsABF1 showed increased sensitivity to d-allose in rice. These findings indicated that the phosphorylation of d-allose at C6 by hexokinase is essential and OsABF1 is involved in the signal transduction for d-allose-induced growth inhibition. [ABSTRACT FROM AUTHOR]

The gene coding for ribose-5-phosphate isomerase (Rpi) from Thermotoga lettingae TMO was cloned and expressed in E. coli. The recombinant enzyme was purified by Ni-affinity chromatography. It converted d-psicose to d-allose maximally at 75 °C and pH 8.0 with a 32 % conversion yield. The k, turnover number ( k), and catalytic efficiency ( k k) for substrate d-psicose were 64 mM, 6.98 min and 0.11 mM min respectively. [ABSTRACT FROM AUTHOR]

D-Allose, a C3 epimer of D-glucose, has potential to improve human health as a functional food. However, its effect on the intestinal environment remains unknown. Aged humans progressively express changes in the gut, some of which deleteriously affect gastrointestinal health. In this study, we profiled the intestinal microbiome in aged mice and analyzed organic acids produced by bacteria in cecum contents after long-term ingestion of D-allose. D-Allose did not significantly change organic acid concentration. However, long-term ingestion did significantly increase the relative abundance of Actinobacteria and reduce the relative abundance of Proteobacteria. These results suggest that oral D-allose improves the proportion of favorable intestinal flora in aged mice. D-Allose significantly decreased the relative abundance of Lachnospiraceae bacteria, but increased the relative abundance of Bacteroides acidifaciens and Akkermansia muciniphila . Thus, D-allose might serve as a nutraceutical capable of improving the balance of gut microbiome during aging., (2022 by The Japanese Society of Applied Glycoscience.)

Cisplatin (cis-diamminedichloroplatinum II) is a potent antineoplastic agent widely used to treat various forms of cancer. However, its therapeutic use is limited because of dose-dependent nephrotoxicity. Inflammatory mechanisms may play an important role in the pathogenesis of cisplatin nephrotoxicity. D-allose is an aldo-hexose present in nature that recently has been demonstrated to inhibit production of inflammatory mediators in septic kidneys. The purpose of this study was to determine the protective effects of D-allose on cisplatin-induced nephrotoxicity. Cisplatin (20 mg/kg) was administered by intraperitoneal injection to mice in the cisplatin group and the cisplatin plus D-allose group, as was normal saline to control group mice. D-allose was intraperitoneally administered immediately after cisplatin injection. Serum and renal tumor necrosis factor (TNF)-alpha concentrations, renal monocyte chemoattractant protein-1 (MCP-1; a chemotactic factor for monocytes), renal function, histological changes and renal cortex neutrophil infiltration were determined 72 h after cisplatin injection. The serum TNF-alpha concentration in the cisplatin plus D-allose (400 mg/kg body weight) group significantly decreased in comparison with that in the cisplatin group. The renal TNF-alpha and MCP-1 concentrations in the cisplatin plus D-allose group significantly decreased in comparison with those in the cisplatin group. Neutrophil infiltration in the cisplatin plus D-allose group was significantly lower than that in the cisplatin group. Cisplatin-induced renal dysfunction and renal tubular injury scores were attenuated by D-allose treatment. These results reveal that D-allose attenuates cisplatin-induced nephrotoxicity by suppressing renal inflammation. Hence, D-allose may become a new therapeutic candidate for treatment of cisplatin-induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

Abstract: Oxidative stress modulates the osteoclast differentiation via redox systems, and thioredoxin 1 (Trx) promotes the osteoclast formation by regulating the activity of transcription factors. The function of Trx is known to be regulated by its binding partner, thioredoxin-interacting protein (TXNIP). We previously reported that the expression of TXNIP gene is strongly induced by a rare sugar d-allose. In this study, we tested the hypothesis that d-allose could inhibit the osteoclast differentiation by regulating the Trx function. We used a murine Raw264 cell line that differentiates to the osteoclast by the receptor activator of nuclear factor-κB ligand (RANKL) treatment. The effect of sugars was evaluated by tartrate-resistant acid phosphatase staining. The expression and localization of TXNIP and Trx protein were examined by Western blotting and immunohistochemisty. The activity of the nuclear factor-κB, nuclear factor of activated T cells, and activator protein 1 transcription factors was measured by the luciferase reporter assay. The addition of d-allose (25 mmol/L) inhibited the osteoclast differentiation down to 9.53% ± 1.27% of a receptor activator of nuclear factor-κB ligand–only treatment. During the osteoclast differentiation, a significant increase of TNXIP was observed by d-allose treatment. The immunohistochemical analysis showed that both Trx and TXNIP existed in the nucleus in preosteoclasts and osteoclasts. Overexpression of TXNIP by plasmid transfection also inhibited the osteoclast formation, indicating the functional importance of TXNIP for the osteoclast differentiation. Transcriptional activity of the activator protein 1, nuclear factor-κB, and nuclear factor of activated T cells, known to be modulated by Trx, were inhibited by d-allose. In conclusion, our data indicate that d-allose is a strong inhibitor of the osteoclast differentiation, and this effect could be caused by TXNIP induction and a resulting inhibition of the Trx function. [Copyright &y& Elsevier]

Abstract: The anti-oxidative activity of the rare sugar D-allose has recently been reported, but the mechanism is largely unclear. In this study, we evaluated the reactive oxygen species (ROS) scavenging activities of D-allose and then examined the effects of D-allose on ROS production in mitochondria to clarify the antioxidant properties of D-allose. While D-allose did not scavenge hydrogen peroxide and superoxide anions, it eliminated hydroxyl radicals to the same extent as D-glucose. Rotenone, an uncoupler of mitochondrial respiratory complex I, induces ROS production in mouse neuroblastoma Neuro2A cells in the presence of D-glucose. However, in the presence of D-allose, there was no change in the ROS levels in Neuro2A cells following rotenone treatment. Furthermore, treatment with D-allose attenuated the D-glucose-dependent ROS generation induced by rotenone. Whereas treatment with D-glucose enhanced ATP synthesis in Neuro2A cells, D-allose was less effective in producing intracellular ATP than D-glucose. Treatment with D-allose inhibited the ATP synthesis stimulated by D-glucose. These results suggest that D-allose suppresses ROS production in the mitochondria due to competition with D-glucose at the cellular level. [Copyright &y& Elsevier]

One of the rare sugars, d-allose, which is the epimer of d-glucose at C3, has an inhibitory effect on rice growth, but the molecular mechanisms of the growth inhibition by d-allose were unknown. The growth inhibition caused by d-allose was prevented by treatment with hexokinase inhibitors, d-mannoheptulose and N-acetyl- d-glucosamine. Furthermore, the Arabidopsis glucose-insensitive2 ( gin2) mutant, which is a loss-of-function mutant of the glucose sensor AtHXK1, showed a d-allose-insensitive phenotype. d-Allose strongly inhibited the gibberellin-dependent responses such as elongation of the second leaf sheath and induction of α-amylase in embryo-less half rice seeds. The growth of the slender rice1 ( slr1) mutant, which exhibits a constitutive gibberellin-responsive phenotype, was also inhibited by d-allose, and the growth inhibition of the slr1 mutant by d-allose was also prevented by d-mannoheptulose treatment. The expressions of gibberellin-responsive genes were down-regulated by d-allose treatment, and the down-regulations of gibberellin-responsive genes were also prevented by d-mannoheptulose treatment. These findings reveal that d-allose inhibits the gibberellin-signaling through a hexokinase-dependent pathway. [ABSTRACT FROM AUTHOR]

Abstract: We examined the effects of a rare sugar, d-allose, which is 6-carbon monosaccharide, on endocytosis and T cell stimulation by dendritic cells (DCs). The endocytosis of BCG-anti-BCG immune complexes by DCs markedly decreased in d-allose-containing medium. Co-culture with T cells (mixed leukocyte reaction, MLR) of DCs, which had been exposed to BCG in d-allose-supplemented medium, induced apoptosis of CD4+ T cells in a manner dependent on d-allose concentration. After the MLR, DCs cultured in the medium with d-allose expressed less CD40 and more Fas ligands than those cultured without d-allose. It was suggested that the functions of DCs, internalization, processing and the subsequent antigen presentation to T cells, are down-regulated via the action of d-allose. [Copyright &y& Elsevier]

d-Allose has attracted a great deal of attention in recent years due to its many pharmaceutical activities, which include anti-cancer, anti-tumor, anti-inflammatory, anti-oxidative, anti-hypertensive, cryoprotective, and immunosuppressant activities. d-Allose has been produced from d-psicose using d-allose-producing enzymes, including l-rhamnose isomerase, ribose-5-phosphate isomerase, and galactose-6-phosphate isomerase. In this article, the properties, applications, and metabolism of d-allose are described, and the biochemical properties of d-allose-producing enzymes and their d-allose production are reviewed and compared. Moreover, several methods for effective d-allose production are suggested herein. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to investigate the radiosensitizing potential of d-allose in human head and neck cancer cells. HSC-3 cells were treated with or without d-allose for 6h and then irradiated (2–6Gy). The combination of d-allose and radiation was more effective than either agent alone. The radiation enhancement ratios at the 37% survival level were 1.61 and 2.11 for 10mM and 25mM d-allose treatment, respectively. The combination of d-allose and radiation also reduced the cell proliferation in 3D culture experiments. Although the mRNA expression of TXNIP was not increased by radiation alone, combined use with d-allose markedly elevated TXNIP expression. The combination of d-allose and radiation significantly induced intracellular reactive oxygen species (ROS) and apoptosis compared to that induced by either agent alone. This study shows that d-allose enhances the effect of radiation, suggesting a potential clinical application of combination treatment with d-allose and radiation for head and neck cancer. [Copyright &y& Elsevier]

Purpose: To investigate the protective effects of d-allose, a rare sugar, on pressure-induced ischemia during vitrectomy in the rabbit eye. Methods: The rabbits underwent pars plana vitrectomy, and continuous intraocular irrigation at a perfusion pressure of 140 mmHg was performed for 45 min. Intraocular pressure was regulated by adjusting the height of a bottle of balanced saline solution containing d-allose. Morphometric studies were performed to study the effects of d-allose on the histological changes induced by ischemia in the rabbit retina. Electroretinograms (ERGs) were taken before and 1 and 7 days after vitrectomy. Nitroblue tetrazolium was used as an index of superoxide anion (O) generation. Data were analyzed by use of the unpaired Student's t test. Results: Seven days after ischemia, significant reductions in both number of ganglion cells and the thickness of the inner plexiform layer were observed. d-Allose significantly inhibited ischemic injury of the inner retina ( P < 0.05). On postoperative day 7, amplitudes of ERG b-waves were significantly lower in the control group than in the d-allose group ( P < 0.05). d-Allose suppressed the production of O. Conclusions: Intraocular irrigation with d-allose during vitrectomy may protect the retina against ischemia-induced damage. [ABSTRACT FROM AUTHOR]

Ribose-5-phosphate isomerase from Clostridium thermocellum converted d-psicose to d-allose, which may be useful as a pharmaceutical compound, with no by-product. The 12 active-site residues, which were obtained by molecular modeling on the basis of the solved three-dimensional structure of the enzyme, were substituted individually with Ala. Among the 12 Ala-substituted mutants, only the R132A mutant exhibited an increase in d-psicose isomerization activity. The R132E mutant showed the highest activity when the residue at position 132 was substituted with Ala, Gln, Ile, Lys, Glu, or Asp. The maximal activity of the wild-type and R132E mutant enzymes for d-psicose was observed at pH 7.5 and 80°C. The half-lives of the wild-type enzyme at 60°C, 65°C, 70°C, 75°C, and 80°C were 11, 7.0, 4.2, 1.5, and 0.6 h, respectively, whereas those of the R132E mutant enzymes were 13, 8.2, 5.1, 3.1, and 0.9 h, respectively. The specific activity and catalytic efficiency ( k/ K) of the R132E mutant for d-psicose were 1.4- and 1.5-fold higher than those of the wild-type enzyme, respectively. When the same amount of enzyme was used, the conversion yield of d-psicose to d-allose was 32% for the R132E mutant enzyme and 25% for the wild-type enzyme after 80 min. [ABSTRACT FROM AUTHOR]

Abstract: Rare sugars are defined as monosaccharides and their derivatives that rarely exist in nature, according to the International Society of Rare Sugars. d-Allose (3-epi d-glucose) is one of the rare sugars, for which various physiological activities have recently been found, with increasing attention to its applications to bio-industry. Until now, however, there is no convenient method of measuring these sugars in a specific manner. For detecting d-allose, three consecutive enzyme reactions were devised by fabricating of a reaction batch chamber packed with l-rhamnose isomerase (LRI), d-tagatose 3-epimerase (DTE) and a screen-printed electrode, on which d-fructose dehydrogenase (DFDH) was immobilized. To obtain a substantial sensing system, extensive experimental parameters were optimized. These included the concentration of photo-crosslinkable poly (vinyl alcohol) bearing stilbazolium groups (PVA-SbQ), reaction ratios, and temperature of the batch chamber. By adopting the three consecutive enzyme reactions, an undesirable reverse reaction was minimized. As a result, the developed sensor system exhibited a good linear response on d-allose in the range from 0.1 to 50mM (r 2 =0.998). The system has an apparent advantage over the previous chromatography approach in terms of simplicity and inexpensiveness. [Copyright &y& Elsevier]

Objectives: This study was aimed to investigate the relationship between the antiproliferative effects of D-allose and the up-regulation of thioredoxin-interacting protein (TXNIP) in head and neck cancer cells. Methods: For the in vitro study, 5 oral squamous cell carcinoma cell lines (Ca9-22, HSC-3, HSC-4, SAS, and KON) were treated with 25 mmol/L D-allose. For the in vivo study, HSC-3 cells were used in a xenograft model with female athymic nude mice (BALB/c nu/nu; 5 to 6 weeks old). Results: Inhibition of cell growth by D-allose was noted in HSC-3 and Ca9-22 cells, along with significant induction of TXNIP. Although TXNIP up-regulation was also evident, albeit to a lesser extent, in the remaining cell lines, D-allose did not inhibit their growth. With the HSC-3 line, the cell survival fractions decreased and TXNIP expression increased in a D-allose dose-dependent manner. The antiproliferative effects were partially suppressed by concomitant D-glucose treatment, which also reduced TXNIP expression. In the in vivo experiment, the tumor volume at day 15 after D-allose treatment was reduced to 61% of that of the control group. Conclusions: This study showed that D-allose exerts growth inhibitory effects on head and neck cancer cells in vitro and in vivo. The sugar may act as an antiproliferative agent via TXNIP induction and thus may be useful as a novel anticancer drug. [ABSTRACT FROM AUTHOR]

Background An inhibitory effect of D-allose, a rare sugar, on several cancer cell lines has been reported. This study aimed to investigate the growth inhibition of head and neck squamous cell carcinoma cells by D-allose. Methods We treated 3 head and neck carcinoma cell lines with D-allose, D-fructose, D-psicose, and D-glucose. Cell growth assays as well as analyses of messenger RNA (mRNA) expression, cell cycle, apoptosis, and uptake of 14C-glucose were performed. Results D-allose had inhibitory effects on all 3 cell lines and tended to upregulate mRNA expression of glucose transporters, p21 and p53, and downregulate mRNA expression of cyclin A2, cyclin B1, and CDC2. We observed that D-allose tended to interfere with the intracellular uptake of D-glucose and induced apoptosis. Conclusion Our results indicate that D-allose inhibits the growth of head and neck squamous cell carcinoma cells. D-allose has a considerable potential as a new anticancer agent in those patients. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [ABSTRACT FROM AUTHOR]

Abstract: d-Allose, the C-3 epimer of d-glucose, is one of the rare sugars found in nature. In the present study, we have elucidated for the first time that various leukemia cell lines have different susceptibility to anti-proliferative activity of d-allose, and that this difference is related to the difference in induction of thioredoxin interacting protein (TXNIP) expression. We examined 5 leukemia cell lines (MOLT-4F, IM-9, HL-60, BALL-1 and Daudi), and found that MOLT-4F (T-cell lymphoblastic leukemia) had the highest susceptibility to d-allose, and that Daudi (Burkitt''s lymphoma) had the lowest. d-Allose significantly slowed the cell cycle progression without causing apoptosis of MOLT-4F cells. Intracellular TXNIP expression was specifically and markedly enhanced in MOLT-4F cells by d-allose treatment, and subsequent increase of p27kip1, a cell cycle inhibitor, was observed. On the other hand, d-allose did not increase TXNIP and p27kip1 levels at all in Daudi cells. These results indicate that d-allose suppresses MOLT-4F cell proliferation possibly by the inhibition of cell cycle progression via induction of TXNIP expression. [Copyright &y& Elsevier]

• d -allose significantly reduced the IgG/IgE-binding ability of α-lactalbumin (α-LA) glycated. • ELISA and basophil degranulation were used to evaluate the allergenicity of α-LA glycated with d -allose. • The digestibility of α-LA glycated with d -allose was significantly reduced. • The glycation extents in terms of glycated sites and DSP were analyzed by LC Orbitrap MS/MS. • This study gave relationships between allergenicity and digestibility and glycated sites. The mechanism of d -allose in reducing the allergenicity and digestibility of ultrasound-pretreated α-lactalbumin (α-LA) was studied. The intensity reduction and peak red shift occurred in fluorescence spectra of glycated samples. Enzyme-linked immunosorbent assay and basophil degranulation analysis showed that d -allose significantly reduced the allergenicity of α-LA, and ultrasound-pretreated α-LA showed the lowest allergenicity after glycation. Compared with α-LA, the degree of hydrolysis decreased in glycated samples. Size-exclusion high-performance liquid chromatography showed that the glycated α-LA was resistant to digestive enzymes. The glycated sites and average degree of substitution per peptide molecule were determined using LC Orbitrap MS/MS. These results suggested that the masking of linear allergenic epitopes by glycation could reduce the allergenicity. Therefore, the combination of ultrasound pretreatment and glycation is a potential method to reduce protein allergenicity in food processing and provides a useful approach for the application of rare sugars in food processing. [ABSTRACT FROM AUTHOR]

d-Allose is a novel anti-tumor monosaccharide that causes cell growth inhibition, specifically of the cancer cells, by inducing the tumor suppressor gene thioredoxin interacting protein (TXNIP). The commonly used anti-tumor drug, 5-fluorouracil (5-FU), blocks the cell cycle by inhibiting thymidylate synthase, and is also known to induce TXNIP gene expression. In this study, we examined the synergistic effect of d-allose and 5-FU and the role of TXNIP on cancer cell growth. The treatment of HuH-7 cells with d-allose or 5-FU inhibited the cell growth in a dose-dependent manner (75.2±2.7% with 50 mM d-allose and 66.1±2.7% with 0.5 μg/ml 5-FU) and d-allose enhanced the anti-tumor effect of 5-FU (55.3±1.1 %). TUNEL analysis did not show any evidence of apoptosis with either d-allose or 5-FU treatment. 5-FU suppressed the expression of p27kip1, p53, and cyclin E, whereas d-allose induced p53 and reduced cyclins D, A, and E. The expression of p27kip1 remained unchanged by d-allose at transcriptional level, but increased at the protein level suggesting an increase in protein stability by TXNIP. d-Allose and to a lesser extent 5-FU induced TXNIP expression significantly (808.4±122.9% and 186.8±32.9%, respectively) and the combination of both further enhanced TXNIP expression. As d-allose has no known side effects on normal cells, the combination of d-allose and 5-FU might be a potent candidate for cancer therapy. [Copyright &y& Elsevier]

Development of effective agents for treatment of hormone-refractory prostate cancer (HRPC) has become a national medical priority. d-Allose is a monosaccharide (C-3 epimer of glucose) distributed rarely in nature; because of its scarcity and cost, the biological effect has hardly been studied. In the present study, we demonstrated the inhibitory action of d-allose on proliferation of human HRPC cell lines, DU145 and PC-3 in a dose- and time-dependent manner, while human normal prostate epithelial (NPE) cell line, PrEC showed no remarkable effect. In vitro treatment of d-allose resulted in the alteration of Bcl-2/Bax ratio in favor of apoptosis (programmed cell death, PCD) in both the HRPC cell lines, which was associated with the lowering of mitochondrial transmembrane potential (Δψm) and the release of cytochrome C (cyt C), the cleavage of caspase 3 and poly (ADP-ribose) polymerase (PARP), and the elevation of calcium concentration in cytosol ([Ca2+]c). d-Allose also induced G1 phase arrest of the cell cycle in DU145 cell line. This study for the first time suggested the antiproliferative effect of d-allose through induction of PCD in HRPC cell lines, which could be due to the modulation of mitochondria mediated intrinsic apoptotic pathway. [ABSTRACT FROM AUTHOR]

d-Allose is a monosaccharide. We previously reported that d-allose attenuated renal injury by inhibiting the activation of neutrophils after renal ischemia/reperfusion. Lipopolysaccharide (LPS) triggers sepsis syndrome by activating monocytes to produce proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha, which potently stimulates the activation of neutrophils. This study was undertaken to examine the effects of d-allose on renal injury in the systemic inflammatory response induced by LPS administration, with emphasis on systemic TNF-alpha and the activation of neutrophils in the rat kidney. Serum and renal TNF-alpha, renal cytokine-induced neutrophil chemoattractant (CINC)-1, and myeloperoxidase (MPO) concentrations, and renal function after LPS administration were evaluated. d-Allose (400 mg/kg body weight) inhibited LPS-induced increases in serum and renal TNF-alpha concentrations and renal CINC-1 and MPO concentrations after LPS administartion, as well as the subsequent neutrophil-mediated renal injury. These findings may have important implications in understanding the biologic functions of d-allose. d-Allose may prove useful in protecting against acute renal injury in systemic inflammatory responses to LPS. [Copyright &y& Elsevier]

d-Allose, the C-3 epimer of d-glucose, is a monosaccharide present in minute quantities in nature and a rare sugar. The effects of d-allose on diethyl nitrosamine (DEN)-induced hepatocarcinogenesis were examined in male F344 rats by a rat medium-term bioassay based on the two-step model of hepatocarcinogenesis (experiment 1). In addition, a DNA microarray analysis was employed to clarify possible mechanisms of action of d-allose (experiment 2). The antioxidation potential of d-allose solution itself or of serum in rats treated with d-allose was also examined directly by measuring Cu+-reducing antioxidation power (experiment 3). Furthermore, to investigate the effects of d-allose in vivo under conditions of oxidative stress, it was administered with a choline-deficient, l-amino acid-defined diet (CDAA) in the medium-term liver carcinogenesis bioassay (experiment 4). Experiment 1 demonstrated no effects of d-allose on the development of glutathione S-transferase placental form (GST-P) positive foci in the liver. From DNA microarray analysis, several mRNA markers were found to be altered with functions related to apoptosis and cell proliferation (experiment 2), although d-allose itself and serum in vivo exhibited no antioxidation power directly (experiment 3). When d-allose was administered with the CDAA diet, decreases in the area and number of GST-P positive foci were noted with P values of 0.158 for area (%) and 0.061 for number (/cm2) (experiment 4). These results suggest the potential inhibitory effect of d-allose on liver carcinogenesis, particularly under oxidative stress conditions. [Copyright &y& Elsevier]

Abstract: We purified recombinant galactose 6-phosphate isomerase (LacAB) from Lactococcus lactis using HiTrap Q HP and Phenyl-Sepharose columns. The purified LacAB had a final specific activity of 1.79units/mg to produce d-allose. The molecular mass of native galactose 6-phosphate isomerase was estimated at 135.5kDa using Sephacryl S-300 gel filtration, and the enzyme exists as a hetero-octamer of LacA and LacB subunits. The activity of galactose 6-phosphate isomerase was maximal at pH 7.0 and 30°C, and enzyme activity was independent of metal ions. When 100g/L of d-psicose was used as the substrate, 25g/L of d-allose and 13g/L of d-altrose were simultaneously produced at pH 7.0 and 30°C after 12h of incubation. The enzyme had broad specificity for various aldoses and ketoses. The interconversion of sugars with the same configuration except at the C2 position was driven by using a large amount of enzyme in extended reactions. The interconversion occurred via two isomerization reactions, i.e., the interconversion of d-allose↔ d-psicose↔ d-altrose, and d-allose to d-psicose reaction was faster than d-altrose to d-psicose reaction. [Copyright &y& Elsevier]

Abstract: d-Allose, an aldo-hexose, is a rare sugar whose biological functions remain largely unclear. Recently, we demonstrated a novel inhibitory effect of d-allose on production of reactive oxygen species (ROS). Here, we focused on investigating cryoprotective effects of d-allose on cell viability. Mammalian cell lines including OVCAR-3 (human ovarian cancer), HeLa (human cervical cancer), HaCaT (human skin keratinocytes), HDF (human dermal fibroblasts) and NIH3T3 (murine fibroblasts) cells were frozen at −80°C in culture media with various d-allose concentrations. Cells were allowed to recover for 24h, 1 week or 1 month prior to survival assessment using the trypan blue dye exclusion test, when cell proliferation was evaluated by MTT assay. A beneficial protective role of d-allose on cell survival was found, similar to that of trehalose (disaccharide of glucose), a recognized cryoprotectant. The results suggest that d-allose as a sole additive may provide effective protection for mammalian cells during freezing. Practical studies now need to be performed with d-allose, for example to determine optimal freezing protocols and explore potential for preservation of tissues or organs at non-freezing temperatures. [Copyright &y& Elsevier]

d-Allose is one of the rare sugars produced from d-psicose. We examined whether d-allose reduces the extent of rat renal ischemia/reperfusion (I/R) injury by suppressing the activation of neutrophils. The renal concentrations of cytokine-induced neutrophil chemoattractant (CINC)-1 and myeloperoxidase were significantly increased after renal I/R. These increases were significantly inhibited by d-allose administration. Furthermore, d-allose significantly inhibited the increase in the concentrations of blood urea nitrogen (BUN), creatinine, N-acetyl β-d-glucosaminidase (NAG) and histopathologic changes after renal I/R. These findings strongly suggest that d-allose protects against I/R-induced renal injury by inhibiting the activation of neutrophils that play an important role in I/R-induced renal injury. These findings may have important implications in understanding the biologic functions of d-allose. d-Allose may prove useful in renal surgery and transplantation. [Copyright &y& Elsevier]

The rpiB gene, encoding ribose-5-phosphate isomerase (RpiB) from Clostridium thermocellum, was cloned and expressed in Escherichia coli. RpiB converted d-psicose into d-allose but it did not convert d-xylose, l-rhamnose, d-altrose or d-galactose. The production of d-allose by RpiB was maximal at pH 7.5 and 65°C for 30 min. The half-lives of the enzyme at 50°C and 65°C were 96 h and 4.7 h, respectively. Under stable conditions of pH 7.5 and 50°C, 165 g d-allose l− 1 was produced without by-products from 500 g d-psicose l−1 after 6 h. [ABSTRACT FROM AUTHOR]

Abstract: l-Rhamnose isomerase (l-RhI) from Pseudomonas stutzeri LL172 can convert d-psicose to d-allose. Partially purified recombinant l-RhI from Escherichia coli was immobilized on BCW-2510 Chitopearl beads and utilized to produce d-allose. Total 20,000 units of immobilized enzyme converted d-psicose to d-allose without remarkable decrease in the enzyme activity over 17 days. When 50% d-psicose (w/w) was applied to a column with a flow rate of 0.8ml/min at 42°C, approximately 30% d-psicose was isomerized to d-allose for 17 days. However, by reducing the flow rate to 0.4ml/min after 17 days, d-allose was transformed at the same rate for 13 days. The total of 27l reaction mixture was separated by Simulated-Moving-Bed Chromatograph system. Approximately 2.2l/d of 50% (w/w) reaction mixture was separated continuously. After separation, d-allose and d-psicose fractions were 3l of approximately 10% (w/w) with 95% purity and 10l of approximately 8% (w/w) with 95% purity per day, respectively. The separated d-allose solution was concentrated up to about 50% and crystallized gradually by being kept at room temperature. Crystals of d-allose were separated from the syrup by filtration and 1.65kg crystals of 100% purity were obtained. The d-allose crystal yield from the d-psicose substrate was approximately 10%. [Copyright &y& Elsevier]

The Maillard reaction (MR) is an ubiquitous reaction of condensation of a reducing sugar with amino groups of protein, which may improve the functional and/or biological properties of foods. The present study was carried out to determine the degree of α-lactalbumin (α-LA) conjugation with a rare sugar (d-allose, All) and two alimentary sugars (d-fructose, Fru; d-glucose, Glc) through MR and the extent to which these reactions could convey antioxidant activity to α-LA. The MR was generated in dry state at 50 °C and 55% relative humidity for up to 48 h. The results showed that the conjugation rate and fluorescence development of α-LA modified with All were faster than that of those modified with Glc and Fru, respectively. Furthermore, α-LA modified with All exhibited the highest tetrazolium salt (XTT) reducibility and radical cation (ABTS˙+)-scavenging activity. There was a good correlation between the fluorescence temporal patterns and biochemical activity of the different sugar-protein conjugates. Thus, the protein glycated with All could be used in formulated food as a functional ingredient, with a strong antioxidant activity, for scavenging free radicals and delaying deterioration due to oxidation. [Copyright &y& Elsevier]

Mass production of a rare aldohexose d-allose from d-psicose was achieved in a batch reaction by crude recombinant l-rhamnose isomerase (l-RhI) cross-linked with glutaraldehyde. The d-psicose substrate was, in turn, mass produced from a naturally abundant ketohexose d-fructose by immobilized recombinant d-tagatose 3-epimerase (d-TE). At an equilibrium state, 25% of d-psicose was isomerized to d-allose, that is, 25 g of d-allose was obtained from 100 g of d-psicose. The d-allose product was easily separated and crystallized from the reaction mixture that contains 25%d-allose, 8%d-altrose and 67%d-psicose using ethanol. Empirically, approximately 338 g, that is, 90% of a theoretical overall yield for the purification of pure d-allose crystals was produced from 1.5 kg of d-psicose within 30 d using a constructed bioreactor. The cross-linked enzyme had an operative half-life of two months after repeated usages. [Copyright &y& Elsevier]

d-Allose, a rare sugar, is one of the potent inhibitors of ischemia/reperfusion injury of the rat liver. To investigate the potency of this powerful agent we examined its effect against ischemia/reperfusion injury and compared it to that of allopurinol and superoxide dismutase. Male Lewis rats were given water ad libitum preoperatively for 12 h and anesthetized by isoflurane inhalation anesthesia. Drugs were administered through a polyethylene catheter inserted into the portal vein for 2 h ( d-allose), 10 min (allopurinol), or 5 min (superoxide dismutase) before ischemia, and the livers were then subjected to 70% ischemia, induced by crossclamping the vessels to the lateral and median lobes of the liver for 90 min. Rats were divided into four groups: group 1, pretreated with vehicle (normal saline); group 2, treated with d-allose; group 3, treated with allopurinol; and group 4, treated with superoxide dismutase. The effects of the drugs were evaluated by liver hemodynamics, neutrophil count, myeloperoxidase, liver enzymes, and histological studies. d-Allose improved liver hemodynamics ( P < 0.001) and postischemic animal survival ( P < 0.05) significantly compared with the control group and nonsignificantly compared with the allopurinol and superoxide dismutase groups. Myeloperoxidase activity in the postischemic liver tissue was decreased significantly ( P < 0.05) by d-allose compared with all other treatment and control groups. Neutrophil count was also significantly ( P < 0.05) decreased in the d-allose group compared with than that in the control group, as well as the superoxide dismutase group. Only d-allose produced a statistically significant decrease in the level of liver enzymes, compared with levels in the control group. The moderately protective effect of d-allose, which caused no clinical side effects, is encouraging. d-Allose had the best protective effect against neutrophil-related postischemic injury of the liver tissue, followed by allopurinol and superoxide dismutase. However, a more extensive study is needed to ensure the effects as well as the mechanisms of the effect of this rare sugar. [ABSTRACT FROM AUTHOR]

In this report, Shinella zoogloeoides NN6 was discovered to produce two rare sugar producing enzymes, D-allulose 3-epimerase (DAE) and L-rhamnose isomerase (LRhI), when cultured with L-rhamnose as the sole carbon source. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of purified DAE and LRhI revealed that the molecular masses of the monomeric subunits are 37 and 43 kDa, respectively, whereas gel filtration analysis showed that purified DAE and LRhI are 148 and 162 kDa, respectively, indicating that both enzymes form tetramers. The activity of DAE was the highest at 80°C in acetate buffer (pH 6.5) with Co 2+ , whereas LRhI exhibited maximum activity at 60°C in glycine-NaOH buffer (pH 9.0) with Mn 2+ . A co-immobilized biocatalyst was constructed using DAE (3.2 U) and LRhI (40 U). Activity profile analysis of this co-immobilized biocatalyst revealed that DAE activity was highest at 80°C in acetate buffer (pH 5.5), whereas the highest activity for LRhI was observed at 55°C in sodium phosphate buffer (pH 7.0). D-Allose was produced from 2% (w/w) D-fructose via D-allulose at 60°C and pH 9.0 in a one-pot reaction, providing a mixture of D-glucose, D-fructose, D-allulose and D-allose at a ratio of 1.3:62.7:23.6:12.4. This is the first report describing one-pot D-allose production using LRhI and DAE expressed in a single microorganism.

Various cancer cells require massive amounts of glucose as an energy source for their dysregulated growth. Although D‑allose, a rare sugar, inhibits tumor cell growth via inhibition of glucose uptake, a few cells can survive after treatment. However, the mechanism by which D‑allose‑resistant cells are generated remains unclear. Here, we investigated the properties of D‑allose‑resistant cells and evaluated the efficacy of combined treatment with this rare sugar and antitumor drugs. To this end, we established a D‑allose‑resistant tumor cell line and prepared a C57BL/6J mouse tumor xenograft model using Lewis lung carcinoma (LLC) cells. Xenograft‑bearing mice were treated with D‑allose (9 g/kg) and/or hydroxychloroquine (HCQ, 60 mg/kg), an autophagy inhibitor, for two weeks. Although D‑allose inhibited LLC cell growth in a dose‑dependent manner, a few cells survived. The upregulation of LC3‑II, a classical autophagy marker, and the downregulation of mTOR and its downstream molecule Beclin1 were observed in established D‑allose‑resistant LLC cells, which were more sensitive to cell death induced by HCQ. Similarly, in the tumor xenograft model, the tumor volume in mice co‑treated with D‑allose and HCQ was considerably smaller than that in untreated or HCQ‑treated mice. Importantly, the administration of D‑allose induced autophagy selectively at the tumor site of the xenograft‑bearing mice. These results provide a new therapeutic strategy targeting autophagy which is induced in tumor cells by D‑allose administration, and may be used to improve therapies for lung cancer.

The pear quantity is not consistent with the quality of pear paste products due to different proportions of edible cane sugar (sucrose) added during food processing. To determine sucrose addition rate in pear paste, a mathematical model was established to quantify soluble solid concentration, sucrose-adding ratio and d -allose concentration. Gas chromatography-mass spectrometer (GC-MS) results showed that 18 compounds were detected in pear paste. When the total soluble solids (TSS) concentration of pear paste was constant, there was a negative linear relationship between d -allose content and the Ratio of Sucrose Added (RSA) (0.97 ≤R2 ≤ 0.99)., Accordingly, the mathematical model of TSS-RSA-Allose concentration was fitted. It was found that the theoretical values of the pear paste at varied RSAs were comparable with the actual values under different conditions: 85% of the verified values differed by ≤ 10%. This study provides some reference for product testing departments to analyze products and establish the evaluation standard of sucrose ratioin pear paste. [Display omitted] ● 18 compounds of sugar, acid, amino acid and fatty acid in pear paste are found. ● There is a linear relation between Allose concentration and the ratio of sucrose added. ● Allose can be a characteristic component to detect the sucrose added to pear paste. ● The mathematical model of pear paste to detect ratio of added sucrose is fitted. [ABSTRACT FROM AUTHOR]

[Display omitted] • First reported enzyme engineering work on microbial ribose-5-phosphate isomerase A. • A K124A single mutant showed 45 % activity improvement towards D-allose. • Results of mutagenesis were explained by kinetic and molecular dynamic analyses. • Improved activities on most rare sugar substrates implying application potential. Ribose-5-phosphate isomerase A (RpiA) is of great importance in biochemistry research, however its application in biotechnology has not been fully explored. In this study the activity of RpiA from Ochrobactrum sp. CSL1 (OsRpiA) towards D-allose was engineered based on sequential and structural analyses. Strategies of alanine scanning, rational design and saturated mutagenesis were employed to create three mutant libraries. A single mutant of K124A showed a 45 % activity improvement towards D-allose. The reaction properties of the mutant were analyzed, and a shift of optimal pH and higher thermal stability at low reaction temperatures were identified. The conversion of D-allose was also improved by 40 % using K124A, and higher activities on major substrates were found in the mutant's substrate scope, implying its application potential in rare sugar preparation. Kinetics analysis revealed that K m of K124A mutant decreased by 12 % and the catalytic efficiency increased by 65 % towards D-allose. Moreover, molecular dynamics simulation illustrated the binding of substrate and K124A was more stable than that of the wild-type. The shorter distance and more relax bond angle between the catalytic residue of K124A and D-allose explained the activity improvement in detail. This study highlights the potential of OsRpiA as a biocatalyst for rare sugar preparation, and provides distinct evidences for its catalytic mechanism. [ABSTRACT FROM AUTHOR]

The article presents a study which seeks to determine the acute and sub-chronic toxicity of d-allose in rats. The study used male Wistar rats to examine the effects of acute oral administration and sub-chronic in acquiring data regarding the safety of D-allose as a nutritional substrate. Results showed that not a difference was found among the groups in most of the serum chemical and hematological tests, thus, recommend that D-allose is not toxic to rats.

d -allose is one kind of rare sugar and its biological functions and metabolic pathways in several organisms have been reported, but its function in plants' resistance has not been well understood. In this research, we analyzed the function of d -allose in plant immunity in tomato. The plants which were pretreated with 5 mM d -allose increased the resistance to Botrytis cinerea and Pseudomonas syringae pv. tomato (Pst) DC3000 compared with the plants treated with water, with lighter symptom. The d -allose treatment induced the resistance to B. cinerea and Pst DC3000 maybe through regulating reactive oxygen species (ROS) accumulation and the expression levels of defense-related genes. • We determined the optimal concentration and time for d -allose treatment in tomato. • The d -allose treatment have function on the resistance to B. cinerea and Pst DC3000. It was the first time to report d -allose's function on the resistance against pathogens in tomato. • The d -allose regulate the resistance in tomato maybe through regulating ROS accumulation and defense-related gene expression. We explain the reason from molecular level. [ABSTRACT FROM AUTHOR]

The article focuses on the study of the practical production of 6-O-Octanoyl-D-allose and its biological activity on plant growth. The study involves the transesterification of D-allose with vinyl octanoate using Candida antartica lipase in tetrahydrofuran. The result suggests that the growth-inhibiting activity of 6-O-Octanoyl-D-allose on lettuce seedlings was 6-fold larger than D-allose.

d-Allose, one of the rare sugars produced from d-psicose, has been shown to be effective against reperfusion injury after ischemia and partial hepatectomy in cirrhotic rat liver by improving remnant liver blood flow and survival rates, and decreasing liver enzyme levels and liver tissue injury levels. These findings demand further study of the clinical implications of this sugar in view to the advancing fields of liver surgery and transplantation. [Copyright &y& Elsevier]