epiglucan and Necrosis

Carbon tetrachloride (CCl₄) is a well-established model for screening hepato-protective drugs. The aim of the present study was to evaluate the potential protective effects of a novel soluble β-glucan salecan on acute liver injury induced by CCl₄ in mice and to further explore the underlying mechanisms. Mice were given salecan (40 mg kg⁻¹) or phosphate-buffered saline for 3 days prior to treatment with a single intraperitoneal dose of CCl₄ (1 ml kg⁻¹ body weight). Animals were sacrificed at 0, 12, 24, 48, 72 and 96 h post-injection of CCl₄. Serum liver enzyme levels, histology, lipid peroxidation, glutathione (GSH) content, expression of antioxidant enzymes and hepatocyte proliferation were subsequently evaluated. The serum levels of hepatic enzyme markers were markedly reduced in the salecan pretreatment group compared with the control group. Histopathological examination of the livers revealed that hepatocellular degeneration and necrosis were significantly attenuated at an early stage during CCl₄ intoxication and liver recovery was markedly accelerated at a later stage in salecan pre-administered mice. Furthermore, salecan administration remarkably alleviated lipid peroxidation and restored GSH depletion. Meanwhile, the expression of antioxidant genes was significantly elevated in the salecan-treated group. Interestingly, the administration of salecan remarkably enhanced hepatocyte proliferation in the recovery phase after CCl₄ injection. Taken together, these results demonstrated that salecan exhibits a protective action on acute hepatic injury induced by CCl₄ through attenuating oxidative stress and accelerating hepatocyte regeneration.

Topics: Agrobacterium; Animals; beta-Glucans; Carbon Tetrachloride Poisoning; Cell Proliferation; Chemical and Drug Induced Liver Injury; Gene Expression Regulation, Enzymologic; Glutathione; Lipid Peroxidation; Liver; Liver Regeneration; Male; Mice; Mice, Inbred C57BL; Necrosis; Oxidative Stress; Oxidoreductases; Polysaccharides, Bacterial; Protective Agents; Random Allocation; RNA, Messenger; Solubility

The present study was undertaken to determine the histopathological and quantitative effects of the antineoplastic agent, taxol, on the liver. The protective effects of the strong antioxidant, beta-1,3-D-glucan, against liver damage induced by taxol were also investigated. Mice were divided into four main treatment groups: control, taxol, beta-1,3-D-glucan, and taxol+beta-1,3-D-glucan. Each group was further subdivided into six subgroups, according to time of sacrifice (6, 12, 24, and 48 hours and 7 and 14 days). After the experiments, quantitative and histopathological changes in liver were examined by light microscopy and modern stereological systems. Stereological results indicated that the portal triad area of the taxol group was significantly reduced, compared to the controls at 12 hours, whereas in the taxol plus beta-glucan and beta-glucan groups, the means were similar to those of the controls. There was no statistically significant difference in the numerical density of hepatocytes with time between the control and other groups. The histopathological results indicated an increased, time-dependent degeneration and necrosis of the liver tissues in mice in the taxol group. Regenerative changes in livers of mice in the taxol plus beta-glucan group were observed, when compared with those of the taxol group. Stereological and histopathological results suggest that beta-glucan may reduce taxol-induced hepatic damage by blocking the change in the portal area and suppressing processes leading to necrosis.

Topics: Animals; Antioxidants; beta-Glucans; Chemical and Drug Induced Liver Injury; Drug-Related Side Effects and Adverse Reactions; Free Radical Scavengers; Gastrointestinal Diseases; Glucans; Liver; Liver Diseases; Mice; Necrosis; Oxidative Stress; Paclitaxel; Proteoglycans; Rats; Rats, Sprague-Dawley; Rats, Wistar

In order to establish the reliable cut-off value of galactomannan (GM) antigen as well as that for beta-D-glucan for CNPA diagnosis, we conducted the following study. From 2001 to 2008, in a total of 1511 patients we measured GM and anti-aspergillus antibody simultaneously. These patients had chronic pulmonary disease including old tuberculosis, nontuberculous mycobacteriosis, COPD, and had bullous lung, interstitial lung disease or were suspected to have suspected to have interstitial lung disease. We designated cases as probable CNPA when the sample represented a positive anti-aspergillus antibody. We then analyzed the sensitivity and specificity according to various GM antigen values. When using the GM antigen cut-off value at 0.5, the sensitivity and specificity for CNPA were 63.4% and 68.6% respectively. Using 1.0 for cut-off value resulted in the better specificity for CNPA diagnosis. Similar analysis was performed on beta-D-glucan for CNPA diagnosis. When using D-glucan cut-off value as 20 pg/ml, the sensitivity and specificity for CNPA. These results indicate that the cut-off value of serological examination for infectious disease should be considered by the type of disease.

Topics: Antigens, Bacterial; beta-Glucans; Chronic Disease; Galactose; Humans; Mannans; Necrosis; Proteoglycans; Pulmonary Aspergillosis; Sensitivity and Specificity

Chronic granulomatous disease (CGD), a genetic disorder characterized by the absence of a functional phagocyte NADPH oxidase, is a severe immune deficiency. However, non-infectious hyperinflammation is a second hallmark of the disease. In CGD mouse models, sterile hyperinflammation can be induced by A. fumigatus cell wall preparations. In this study, we used subcutaneous injection of microbial cell walls and cell wall components to identify causes of CGD hyperinflammation and to characterize its histological features. Sterile cell wall preparations from fungi (A. fumigatus, C. albicans, S. cerevisiae), but not from bacteria (S. aureus, P. aeruginosa, E. coli), caused prolonged and severe skin inflammation in CGD mice. To identify fungal cell wall elements responsible for this process, we investigated microbial cell wall-derived monosubstances. Injection of beta(1-3)(1-6)-glucan induced severe hyperinflammation in CGD mice, while other fungal cell components [mannan, (1-3) beta-glucan] or bacterial cell wall components (lipopolysaccharide, lipoteichoic acid) caused no or only moderate inflammation. beta-glucan-induced hyperinflammation was predominantly due to a defect in termination of inflammation, as in the initial stage (2 days), the severity of inflammation and the extent of cell death were comparable in wild-type and CGD mice. At later stages (7 days), beta(1-3)(1-6)-glucan-induced inflammation had subsided in wild-type mice. In contrast, CGD mice showed persistent severe inflammation with central necrosis, containing abundant apoptotic and necrotic cells. In summary, branched fungal beta-glucan induces a severe inflammatory reaction in the absence of phagocyte NADPH oxidase. As opposed to the commonly perceived notion that reactive oxygen species are the cause of cell death, our results demonstrate that tissue necrosis can be caused by the absence of a superoxide-producing enzyme.

Topics: Animals; Bacteria; beta-Glucans; Cell Death; Cell Wall; Dermatitis; Disease Models, Animal; Fungi; Granulomatous Disease, Chronic; Injections, Intradermal; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; NADPH Oxidases; Necrosis; Phagocytes; Skin

A large number of functional foods, including those that contain beta-glucan, have been shown to prevent the development of cancer and other chronic diseases. The aim of the present study was to elucidate its mechanism of action, as well as to understand its effects as an antigenotoxic, anticlastogenic agent, and to determine its capacity to preserve cell viability. The investigation was carried out in the CHO-k1 and CHO-xrs5 cell lines. The cytokinesis-blocked micronucleus assay indicated that the different doses of beta-glucan examined (5, 10, 20 and 40 microg/ml) did not show clastogenic effects. In the CHO-k1 cell line, a chemopreventive effect could be observed in all the protocols tested: pre-treatment (% reduction of 35.0-57.3), simultaneous treatment (simple--5 reduction of 19.7-55.6 and with pre-incubation--of 42.7-56.4) and post-treatment (% reduction of 17.9-37.6). This finding indicates mechanisms of action involving desmutagenesis and bioantimutagenesis, albeit the latter having a lesser role. However, in the repair-deficient CHO-xrs5 cells, beta-glucan did not show a protective effect with post-treatment (% reduction of 2.96), thus supporting the involvement of bioantimutagenesis. The comet assay in CHO-k1 cells demonstrated that beta-glucan has neither a genotoxic nor an antigenotoxic effect. Cell viability tests indicated that beta-glucan preserves cell viability in both cell lines, preventing apoptotic events. These findings suggest that beta-glucan, when present in foods, could provide them with nutraceutical characteristics and act as a dietary supplement, or that beta-glucan could be used in new drug development.

Topics: Acridine Orange; Animals; Antigens; Antimutagenic Agents; Apoptosis; beta-Glucans; Cell Survival; CHO Cells; Comet Assay; Cricetinae; Cricetulus; DNA Damage; DNA Repair; Ethidium; Fluorescent Dyes; Micronucleus Tests; Necrosis; Saccharomyces cerevisiae

Water-soluble derivative of chitin-glucan complex used in our study, carboxymethyl chitin-glucan (CM-CG), enables oral administration without harmful side-effects, which can occur upon parenteral administration of the insoluble fungal beta-D-glucans. The aim of this study was to determine in ex vivo experiments the effects of dietary CM-CG on the level of DNA lesions in primary rat hepatocytes induced by various indirectly acting carcinogens. Multiorgan carcinogen benzo[a]pyrene (BaP); two hepatocarcinogens, dimethyldibenzocarbazole (diMeDBC) and N-nitrosomorpholine (NMOR); as well as a complex mixture of organic compounds adsorbed on ambient air particles (TP-S) were used for this purpose. The amount of DNA lesions was assessed using the comet assay and the micronucleus test. In addition, the mitotic indexes and the frequencies of necrotic and apoptotic cells were evaluated as well. Our results showed that the diet enriched with CM-CG (200 mg/kg of body weight) during 21 days did not induce any negative effect on DNA nor did the mitotic indexes and the frequencies of necrotic and apoptotic cells differ statistically from the controls. On the other hand, the hepatocytes isolated from CM-CG fed animals were more resistant to the action of all genotoxins used in our study [BaP (5-20 microM), diMeDBC (0.2-2 microM), NMOR (3.4-10.2 mM), TP-S (5-20 microM)]. We can conclude that in addition to the known immunopotentiating activity of beta-D-glucans, they can efficiently inhibit the genotoxicity of carcinogens requiring metabolic activation in rat heptocytes.

Topics: Animals; Antimutagenic Agents; Apoptosis; beta-Glucans; Carcinogens; Cells, Cultured; Chitin; Comet Assay; DNA Damage; Dose-Response Relationship, Drug; Glucans; Hepatocytes; Male; Micronucleus Tests; Mitosis; Necrosis; Rats; Rats, Sprague-Dawley

The value of the measurement of (1-->3)-beta-D-glucan, a major and common cell wall constituent of fungi, for diagnosing pulmonary aspergillosis was assessed in comparison with that of conventional examinations. The concentrations of (1-->3)-beta-D-glucan in sera was elevated in 7 out of 8 patients with active aspergillosis, but not in cases without active diseases, except for one sample. Further, the concentrations well reflected the activity of the aspergillosis in each case. Regarding conventional examinations, with the immunodiffusion test it was difficult to detect the present activity of the disease. The radioallergosorbent test was useful for diagnosing bronchopulmonary aspergillosis, but not for other types of aspergillosis. The Aspergillus-specific component, galactomannan, was insensitive and the enzyme-linked immunosorbent assay gave highly variable results. Thus, although the assessment of the specificity of the assay is still necessary, compared with other tests, the assay of (1-->3)-beta-D-glucan has the advantage of diagnosing pulmonary aspergillosis and also of assessing the disease activity.

Topics: Antibodies, Fungal; Aspergillosis; Aspergillosis, Allergic Bronchopulmonary; Aspergillus; beta-Glucans; Enzyme-Linked Immunosorbent Assay; Glucans; Humans; Lung Diseases; Lung Diseases, Fungal; Necrosis; Radioallergosorbent Test