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Biomedical subjects

K Asano

Publications and source records attributed to K Asano.

At least 721 records · Page 40Linked to original sources
PubMedDate not supplied

Production of hydrogen peroxide in cancerous tissue by intravenous administration of sodium 5,6-benzylidene-L-ascorbate.

We investigated whether the antitumor action of sodium 5,6-benzylidene-L-ascorbate (SBA) is mediated via oxidation-involved mechanism, in three different systems: 3'-methyl-4-dimethylaminoazobenzene (DAB)-induced rat hepatocellular carcinoma (in vivo), its homogenate (semi in vivo), and cultured cells (in vitro). Oral intake of DAB irreversibly produced hepatocellular carcinoma in rats, with a maximum incidence of carcinogenesis after 4 months. Intravenous administration of SBA induced vacuolar, eosinophilic degeneration and nuclear debris, producing greater amounts of ESR signal of ascorbate radical and hydrogen peroxide (H2O2)-derived chemiluminescence (CL) (H2O2-CL) in the cancerous tissue than in the normal tissue. When SBA was directly added to the homogenates, higher amounts of ascorbate radical and H2O2-CL were generated in cancerous tissues. When SBA was added to the RPMI1640 medium supplemented with 10% fetal bovine serum, methionine was oxidized to methionine sulfoxide and H2O2 was produced in amounts that sufficiently induce apoptotic cell death in human promyelocytic leukemic HL-60 cells. Cytotoxic activity of SBA was significantly reduced by catalase. These data suggest that antitumor activity of SBA in vivo might at least in part be due to H2O2, produced from SBA.

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Influence of anti-allergic agents on in vivo expression of co-stimulatory molecules in normal mice.

The co-stimulatory signal provided by the interaction between CD28 and its ligands, CD80 and CD86, is critical for T cell activation. Engagement of CD40 and CD40L is also essential for IgE synthesis and secretion. In the present study, we examined the influence of anti-allergic drugs on co-stimulatory molecule (CD40, CD80 and CD86) expression in normal mouse splenocytes by flow cytometry. Treatment of BALB/c mice with azelastine (AZ) at a dose of 50.0 micrograms/kg/day, which is the most effective therapeutic dose, for two weeks scarcely affected the expression of co-stimulatory molecules CD40, CD80 and CD86 on splenocytes, whereas a three-week treatment strongly suppressed the expression of these molecules. We also examined the influence of terfenadine (TR) on co-stimulatory molecule expression. The expression of molecules on splenocytes was inhibited when donor mice were treated orally with 2.0 mg/kg/day of TR for three weeks. However, it was not inhibited during a two-week period treatment. These results suggest that the attenuating effects of anti-allergic agents on the diseases may be explained, in part, by their inhibitory action of co-stimulatory molecule expression.

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Suppressive effects of azelastine hydrochloride on CD40 expression in mice.

The present study was designed to examine the influence of an anti-allergic agent, azelastine hydrochloride (AZ) on a co-stimulatory molecule, CD40 expression in actively sensitized mice. BALB/c mice were sensitized by intraperitoneal injection of two doses of dinitrophenylated-ovalbumin and Al(OH)3 at one-week intervals. The mice were treated orally with 0.1 mg/kg of AZ once a day for 14 days starting the same day of booster sensitization. AZ treatment of mice caused the significant suppression of total serum IgE concentration on Day 21 after the first sensitization. However, AZ treatment scarcely affected IL-4 concentration in aqueous spleen extracts. Flowcytometric analysis revealed the suppressive effects of AZ on CD40 expression on sensitized-spleen cells. These data may suggest that AZ suppresses the production of IgE through the inhibition of CD40 expression.

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Inhibitory action of roxithromycin on tumour necrosis factor-alpha production from mast cells in vitro.

This study was designed to evaluate the effects of roxithromycin (RXM), a newly synthesized macrolide antibiotic, on cytokine production from mast cells. Mast cells, induced by long-term culture of spleen cells from BALB/c mice, were stimulated with 2.5 micrograms/ml concanavalin A in the presence or absence of various concentrations of RXM. The culture supernatants were obtained 24 h after stimulation. RXM caused a reduction in TNF-alpha levels in culture supernatants in a dose dependent manner and was first detected at a concentration of as little as 0.5 microgram/ml. Metabolized RXM (RU 39001, RU 44981, and RU45179) also suppressed TNF-alpha production in a dose dependent fashion with a minimum concentration of 0.5 microgram/ml. However, metabolized RXM, RU 28111, scarcely affected TNF-alpha production from cultured mast cells. These results strongly suggest that RXM inhibits mast cell function, especially inflammatory cytokine production and may result in favorable modification in inflammatory diseases.

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Changes in intracellular concentrations of amino acids and polyamines during the apoptosis of HL-60 cells.

Possible changes in the intracellular concentrations of amino acids and polyamines were investigated during the apoptosis of human promyelocytic leukemic HL-60 cells. Treatment of HL-60 cells with sodium 5,6-benzylidene-L-ascorbate (SBA) or sodium ascorbate induced apoptotic cell death characterized by chromatin condensation, nuclear fragmentation, loss of microvilli, and production of numerous vacuoles and apoptotic bodies. The apoptosis was accompanied by a significant increase in the intracellular concentration of almost all neutral and basic amino acids (regardless of their polarity). On the other hand, the concentration of glutamic acid, the most abundant amino acid in the cells, was significantly reduced. These data suggest the reduced amino acid utilization and possible membrane impairment, especially in SBA-treated cells. Among three major polyamines, the intracellular concentration of putrescine rapidly declined, whereas that of spermidine and spermine was almost unchanged during apoptosis. Conversely, the concentration of putrescine, but not that of spermidine and spermine, was significantly increased during the chemically-induced carcinogenesis of mouse liver tissue. The present study demonstrates that the putrescine level is the most sensitive to the proliferation capability of the cells, among three polyamines, and provides an early marker for apoptosis and proliferation.

Amino Acids↗
PubMedDate not supplied

Tumor-specific action of sodium 5,6-benzylidene-L-ascorbate in N-nitrosodiethylamine-administered mouse model.

In order to elucidate the mechanisms of antitumor action of sodium 5,6-benzylidene-L-ascorbate (SBA), we established a mouse hepatocellular carcinoma model by oral administration of N-nitrosodiethylamine (NDA) and examined the ascorbate radical intensity and putrescine content in the liver. The oral intake of NDA induced precancerous lesion and a significant increase in putrescine content among three major polyamines. When the oral intake of NDA was stopped, morphological changes were reversed. ESR spectroscopy showed that the homogenate of precancerous tissues produced greater amounts of ascorbate radical than that of normal liver tissue. Intravenous administration of SBA 30 minutes before removal of the liver prolonged the higher level of ascorbate radical generation in the homogenate of precancerous tissue. The antitumor activity of SBA might be due to the long-term production of radicals in tumor tissues by its prooxidant action.

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PubMedDate not supplied

Stimulation of monocyte iodination and IL-1 production by tannins and related compounds.

Various tannins and related compounds were compared for their ability to stimulate the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood monocytes. The stimulating activity of most of the monomeric and dimeric hydrolyzable tannins was generally higher than that of the trimeric and tetrameric compounds. Compounds that had dehydrohexahydroxydiphenoyl or chebuloyl groups had considerably less activity than those that had other functional groups (hexahydroxydiphenoyl, valoneoyl, dehydrodigalloyl, isodehydrodigalloyl, lactonized valoneoyl, hellinoyl, euphorbinoyl, dehydroeuphorbinoyl or woodfordinoyl group). The methylated derivative, nonacosa-O-methylcoriariin A, was essentially inactive, suggesting the requirement of a phenolic hydroxyl group. Three condensed tannins ((-)-epicatechin 3-O-gallate (ECG)-dimer, ECG-trimer and ECG-tetramer) significantly stimulated both monocyte iodination and their interleukin-1-like factor production. The results suggest the dependence of stimulation of monocyte iodination by tannins and related polyphenols on molecular weight.

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PubMedDate not supplied

Induction of tumor degeneration by sodium benzylideneascorbate.

Intravenous administration of sodium benzylideneascorbate (SBA) rapidly necrotized inoperable human lung cancer, and induced degeneration of 3'-methyl-4-dimethylaminoazobenzene-induced rat hepatocellular carcinoma (vacuolar, eosinophilic degeneration, nuclear debris) without affecting the serum glutamic oxaloacetic transaminase, gamma-glutamyl transpeptidase and total protein levels. Cultured normal human lung and skin fibroblasts, and human glioma and glioblastoma cell lines were relatively resistant to SBA, when compared to human myelogenous leukemic cell lines. SBA had no apparent host immunopotentiation activity such as stimulation of cytokine action or production; activation of monocyte or polymorphonuclear cells; or modulation of poly (ADP-ribose) glycohydrolase activity. The data suggest that the antitumor activity of SBA might be produced by direct action of authentic SBA or its metabolized form(s), rather than by immunopotentiation of the hosts.

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Functional maturation of monocytes/macrophages induced by PSK subfractions.

When mouse resident peritoneal macrophages were cultured with PSK (Krestin), a protein-bound polysaccharide extracted from Coriolus versicolor, they became enlarged and elongated and expressed higher NBT-reducing activity. PSK stimulated the production of differentiation-inducing factor and cytotoxic factor by the mouse macrophage-like cell line J774.1, and iodination (incorporation of radioactive iodine into an acid-insoluble fraction) and interleukin-1-like factor production by human peripheral blood monocytes. Among four different PSK subfractions, the highest molecular weight fraction (MW greater than 200 kD) was the most potent. Natural and chemically modified glucans had little or no activity. The data suggest that some unique structure of the highest molecular weight fraction of PSK directly stimulates the monocytes/macrophages.

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Mitogenic activity of natural and synthetic lignins against cultured splenocytes.

Various natural lignified materials and synthetic dehydrogenation polymers (the so-called synthetic lignins) prepared from several phenylpropenoids were investigated for their mitogenic activity. All of these materials time- and dose-dependently stimulated the DNA synthesis of isolated mouse splenocytes. However, their stimulating activity was significantly decreased when the splenocytes were pretreated with anti-Thy-1.2 monoclonal antibody and rabbit complement. Natural and synthetic lignins demand attention as potential immunopotentiators.

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