Biomedical subjects

K Satoh

Publications and source records attributed to K Satoh.

At least 1,369 records · Page 76Linked to original sources

PubMedDate not supplied

Inhibition of cytotoxic activity of ascorbate by human cancer patient sera.

Cytotoxic activity of sodium ascorbate against a human glioblastoma T98G cell line was concentration-dependently inhibited by serum in the RPMI1640 medium. The inhibitory effect of sera from pancreatic or stomach cancer patients was significantly higher than that of fetal bovine serum (FBS), with or without heat-inactivation. The cytotoxic activity of sodium ascorbate almost completely disappeared in 60-80% of patient sera. ESR spectroscopy revealed that both patient sera and FBS increased the ascorbyl radical intensity, but to significantly lower extents, as compared with that attained by RPMI1640 medium. The present study suggests the importance of re-evaluating the efficacy of not only ascorbate but also other chemotherapeutic drugs under more physiological conditions.

Aged↗

PubMedDate not supplied

Rounded atelectasis formation following decrease of pleural effusion: a case report.

We present a case of rounded atelectasis (RA) observed continuously following decrease of pleural effusion. The collapsed right lower lobe adjacent to pleural effusion changed its shape from wedge-shaped consolidation with air-bronchogram to oval and flat formation at last. The vessels and bronchi curving into RA were detected by CT and we called it horizontal comettail sign. When a mass is detected following decrease of pleural effusion and vessels and bronchi are curving into the mass, the mass may be diagnosed as RA and no further examination may be necessary.

Bronchography↗

PubMedDate not supplied

Effect of metal ions on radical intensity and cytotoxic activity of ascorbate.

Various metal ions were investigated for their ability to modify the radical intensity and cytotoxic activity of sodium ascorbate or ascorbic acid. The addition of metal ions, such as Cu+, Cu2+, Fe2+, Zn2+, Mn2+ and Fe3+, dose-dependently enhanced the ascorbyl radical intensity whereas Na+, K+, Ca2+ and Mg2+ were totally inactive. The enhancement of ascorbyl radical intensity by metal ions was tightly coupled with the accelerated degradation of ascorbate. Addition of either serum or albumin significantly reduced the stimulation effect of Cu2+, and almost completely eliminated that of Fe3+ and Zn2+. The noncytotoxic concentration of Cu2+ significantly enhanced the cytotoxicity of ascorbate against cultured human glioblastoma T98G cell line. The present data suggest the possible role of metal ions in the regulation of the biological activity of ascorbate.

Ascorbic Acid↗

PubMedDate not supplied

Effect of ascorbate oxidase on radical intensity and cytotoxic activity of ascorbate.

In order to test whether ascorbyl radical can directly induce apoptotic cell death, it was produced by the reaction of sodium L-ascorbate with L-ascorbate oxidase. Sodium L-ascorbate induced cytotoxicity against both human glioblastoma and promyelocytic leukemic cell lines. The addition of ascorbate oxidase significantly enhanced both degradation and radical generation of ascorbate, but completely eliminated its cytotoxic activity against both of these cells. These data demonstrate that the ascorbyl radical is not the sole determinant of apoptosis induction.

Antineoplastic Agents↗

PubMedDate not supplied

Stimulation of ascorbate-induced hypoxia by lignin.

Alkali-lignin, lignin sulfonate or protein-bound polysaccharide (PSK) significantly enhanced the ascorbyl radical intensity and cytotoxic activity of ascorbate, but inhibited the intracellular incorporation of [14C]ascorbic acid. These natural products also enhanced ascorbate-induced oxygen consumption, resulting in the rapid depletion of oxygen from culture medium. Enhancement of oxygen consumption was coupled with elevation of oxidation potential. These data suggest that lignin and PSK stimulate the cytotoxic activity of ascorbate by hypoxia.

Ascorbic Acid↗

PubMedDate not supplied

Effect of alpha-tocopherol on cytotoxicity induced by UV irradiation and antioxidants.

The addition of DL-alpha-tocopherol (vitamin E) at the time of UV irradiation only marginally protects cells from UV-induced cytotoxicity. However, a protective effect of alpha-tocopherol emerged when it was added to the cells before UV irradiation, alpha-Tocopherol was progressively and dose-dependently incorporated into the cells. Washout experiments showed that the intracellular concentration of alpha-tocopherol decreased with an approximate half-life of 14-20 hours, due to the release from the cells and dilution by cell proliferation. Pretreatment of the cells with alpha-tocopherol significantly increased the resistancy against the cytotoxic action of UV irradiation and antioxidants such as sodium ascorbate, gallic acid, n-propyl gallate and caffeic acid. ESR spectroscopy showed that alpha-tocopherol enhanced the ascorbyl radical intensity, whereas it reduced caffeic acid radical intensity, without affecting the radical intensity of gallic acid and n-propyl gallate. Both control and treated cell lysates scavenged superoxide anion (generated by xanthine-xanthine oxidase reaction) and hydroxyl radical (generated by Fenton reaction) to a comparable extent. The present study suggests that the protective effect of alpha-tocopherol might be derived from its incorporation into the cell membranes rather than its scavenging activity.

Antioxidants↗

PubMedDate not supplied

Effect of cysteine, N-acetyl-L-cysteine and glutathione on cytotoxic activity of antioxidants.

The effect of twenty amino acids on the radical intensity of four antioxidants (sodium L-ascorbate, sodium 5,6-benzylidene-L-ascorbate, gallic acid, caffeic acid) was investigated, using ESR spectroscopy. Methionine and methional did not significantly affect the radical intensity of these antioxidants. Methionine sulfoxide slightly enhanced the radical intensity of sodium ascorbate and sodium 5,6-benzylidene-L-ascorbate, but did not that of gallic acid and caffeic acid. Cysteine, N-acetyl cysteine and glutathione significantly reduced the radical intensity and cytotoxic activity of these antioxidants except for sodium 5,6-benzylidene-L-ascorbate. The other amino acids were inactive. The present study further supports that these antioxidants induce cytotoxicity via their pro-oxidant action.

Acetylcysteine↗

PubMedDate not supplied

Effect of copper and iron ions on cytotoxicity induced by ascorbate, gallate and caffeate.

Four antioxidants, sodium ascorbate, gallic acid, n-propyl gallate and caffeic acid, induced apoptotic cell death in human promyelocytic leukemic HL-60 cells. The effects of all these compounds were enhanced by CuCl2 or deferoxamine mesylate, an iron chelator, but were reduced by FeCl3. ESR spectroscopy showed that both CuCl2 and FeCl3 enhanced the ascorbyl radical intensity, but reduced the gallate and caffeate radical intensity. The present data demonstrate that copper and iron ions modify the cytotoxic activity of these antioxidants differently and their radical intensity is not the sole determinant of cytotoxic activity.

Antineoplastic Agents↗

PubMedDate not supplied

Effect of methionine depletion on growth and apoptosis in various tumor cell lines.

Sodium ascorbate, sodium 5,6-benzylidene-L-ascorbate (SBA), gallic acid and caffeic acid induced apoptotic cell death in human myelogenous leukemic cell lines, and stimulated oxidation of methionine into methionine sulfoxide in the culture medium. When various tumor cell lines were cultured in methionine-free medium, their growth was nearly terminated at G1 phase of the cell cycle, producing much smaller number of apoptotic cells. Addition of methionine sulfoxide to the methionine-free medium did not stimulate the apoptosis induction. These data suggest that induction of apoptosis by ascorbates, gallate or by caffeate cannot be simply explained by methionine oxidation.

Antioxidants↗

PubMedDate not supplied

Effect of Trolox, a synthetic analog of alpha-tocopherol, on cytotoxicity induced by UV irradiation and antioxidants.

The addition of Trolox, a synthetic analog of alpha-tocopherol, significantly reduced the cytotoxicity induced by UV irradiation and antioxidants, such as ascorbate, gallate and caffeate. Ascorbate and gallate, but not UV irradiation, stimulated the oxidation of methionine to methionine sulfoxide in the culture medium, possibly because of their prooxidant actions. Trolox slightly, but significantly reduced the methionine oxidation. On the other hand, alpha-tocopherol showed a much lower protective effect against ascorbate and gallate-induced cytotoxicity, and failed to reduce the methionine oxidation induced by these agents. ESR spectroscopy showed that both Trolox and alpha-tocopherol did not significantly change the radical intensity of ascorbate and gallate. The present study suggests that the antioxidative efficacy of Trolox surpasses that of alpha-tocopherol.

Antioxidants↗

PubMedDate not supplied

Radical intensity and differentiation-inducing activity of benzo[a]phenothiazines and phenothiazines.

ESR spectroscopy revealed that 12H-benzo [a]phenothiazine, 9-methyl-12H-benzo[a]phenothiazine, 10-methyl-12H-benzo [a]phenothiazine, 11-methyl-12H-benzo[a]phenothiazine and 5-axo-5H-benzo[a]phenothiazine, which induced the differentiation of human myelogenous leukemic cell lines into maturing macrophages, produced radical(s) under an alkaline condition. On the other hand, 6-hydroxy-5-axo-5H-benzo [a]phenothiazine, 6-methyl-5-oxo-5H-benzo[a]phenothiazine and 5H-benzo[a][1,4]benzothiazino-[3,2-c]phenothiazine, and 13 phenothiazines, which had little or no differentiation-inducing activity, produced no detectable amounts of radical(s). Using Hückel molecular orbital (HMO) method, these active benzo[a]phenothiazines were shown to have the elevated n-spin density at the sulfur atom of their molecules. Seven out of 8 benzo[a]phenothiazines significantly enhanced the radical intensity of sodium L-ascorbate and sodium 5,6-benzylidene-L-ascorbate (SBA), whereas only 3 out of 13 phenothiazines showed similar effects. These data suggest that the induction of human leukemic cell differentiation by benzo[a]phenothiazines might be initiated by radical mediated reactions.

Cell Differentiation↗

PubMedDate not supplied

Copper, but not iron, enhances apoptosis-inducing activity of antioxidants.

Addition of either CuCl or CuCl2 significantly enhanced sodium ascorbate or sodium 5,6-benzylidene-L-ascorbate (SBA)-induced cytotoxicity and internucleosomal DNA cleavage in human promyelocytic leukemic HL-60 cells. On the other hand, the addition of either FeCl2 or FeCl3 inhibited the cytotoxic activity of ascorbate. These effects were observed even if the cells were exposed for only 20 minutes to metals and ascorbates. Copper also stimulated the gallate or caffeate-induced apoptotic cell death, whereas iron was inhibitory. Both copper and iron enhanced the radical intensity of ascorbates, but slightly reduced the radical intensity of gallate and caffeate, suggesting that radical intensity is not the sole determinant of apoptosis induction. Metals did not significantly change the methionine oxidation stimulated by ascorbate, gallate or caffeate. Methionine oxidation may not be indispensable for antioxidant-induced apoptosis.

Antioxidants↗

PubMedDate not supplied

Radical modulation activity of benzo[a]phenothiazine.

12H-Benzo[a]phenothiazine generated radical(s) under alkaline conditions, and enhanced the radical intensity of sodium ascorbate and sodium 5,6-benzylidene-L-ascorbate. Phenothiazine and chlorpromazine hydrochloride did not produce radicals, nor affect the radical intensity of ascorbates. 12H-Benzo[a]phenothiazine scavenged the superoxide anion and hydroxyl radical, more efficiently than phenothiazine and chlorpromazine hydrochloride. The radical modulation activity of 12H-benzo[a]phenothiazine might explain at least in part the ability of this compound to induce monocytic differentiation and apoptosis in human myelogenous leukemic cell lines.

Antioxidants↗

PubMedDate not supplied

Methionine oxidation and apoptosis induction by ascorbate, gallate and hydrogen peroxide.

Addition of either ascorbate, gallate, caffeate or hydrogen peroxide to the culture medium stimulated the oxidation of free methionine to methionine sulfoxide, regardless of the presence or absence of the cells. In methionine-free medium, growth of human myelogenous leukemic cell lines was nearly stopped by G1 arrest, without induction of internucleosomal DNA cleavage. Methionine sulfoxide, a major oxidation product of methionine, was neither growth-promoting nor cytotoxic. On the other hand, methional, a deamination and decarboxylation product of methionine, was highly cytotoxic. The present study suggests that the apoptosis induction by these antioxidants and oxidant cannot simply be explained by methionine oxidation or depletion.

Antioxidants↗

PubMedDate not supplied

Effect of metals and their antagonists on the radical intensity and cytotoxicity of ascorbates.

Five heavy metal antagonists were compared for their specificity of chelating action against copper (CuCl, CuCl2) and iron (FeCl2, FeCl3). ESR spectroscopy showed that both copper and iron significantly enhanced the radical intensity of ascorbate and sodium 5,6-benzylidene-L-ascorbate (SBA). Equimolar concentrations of dimercaprol efficiently chelated all these metals, thus significantly reducing their stimulation effects. On the other hand, the chelating action of penicillamine, ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid was limited to CuCl and CuCl2 whereas deferoxamine mesylate (DFO) was a specific iron chelator. The cytotoxic activity of sodium ascorbate was augmented by DFO, but diminished by FeCl3. The simultaneous addition of DFO and FeCl3 counteracted each other, thus neutralizing their individual effects. The cytotoxic activity of both sodium ascorbate and SBA was significantly enhanced by CuCl2 and this stimulation effect of CuCl2 was effectively chelated by DTPA. The present study demonstrates the specificity of the chelating action of these five antagonists, suggesting the possible application of these different types of antagonists for the prevention of the pathogenic diseases catalyzed by the corresponding metals.

Ascorbic Acid↗

PubMedDate not supplied

Relationship between biological activity and dipole moment in benzo[a]phenothiazines.

Relationship between the biological activity and two different dipole moments were investigated in 9 benzo[a]phenothiazines [1-8] by calculating the dipole moment with the PM3 method. 12H-Benzo[a]phenothiazine [1], 9-methyl-12H-benzo[a]phenothiazine [2], 10-methyl-12H-benzo[a]phenothiazine[3] and 11-methyl-12H-benzo[a]phenothiazine [4] induced monocytic differentiation of human myelogenous leukemic cell lines and displayed antitumor activity. These active compounds showed a significantly smaller value of calculated ground-state dipole moment (mu g) and larger value of first excited-state dipole moment (mu e). The mu e/mu g ratio of four active compounds [1-4] ranged from 3.25 to 4.38, whereas that of three inactive compounds [5,6,7] ranged from 1.77 to 2.72. These two different dipole moments might be useful parameters for estimation of the biological activity of benzo[a]phenothiazines [1-8].

Animals↗

PubMedDate not supplied

Rapid determination of ascorbate by ESR spectroscopy.

Optimal conditions for the determination of ascorbate, based on the detection of its radical by ESR spectroscopy, were established. The optimal pH for the measurement of the ascorbate radical was 10, whereas that for the gallate and caffeate radical was much higher. This was due to the liability of the ascorbate radical at higher pH. When the radical intensity of ascorbate vs. concentration was plotted double logarithmically, a linear correlation was established between these two parameters within the ascorbate concentration of 0.03-10 mM. ESR analysis of the homogenates under alkaline condition demonstrated that ascorbate is distributed in various mouse organs and that the ascorbate radical is unstable at neutral pH in the brain and liver, suggesting the presence of metabolizing substances. The present study suggests the applicability of the present technique for the study of ascorbate metabolism and identification of physiological factors which regulate the radical intensity of ascorbate.

Animals↗

PubMedDate not supplied

Modulating factors of radical intensity and cytotoxic activity of ascorbate (review).

Ascorbate acts both as an antioxidant and as an oxidant, depending upon the environment in which the molecule is present. We have reported that millimolar concentrations of ascorbate induced apoptotic cell death, characterized by cell shrinkage, nuclear fragmentation and internucleosomal DNA cleavage, in human myelogenous leukemic cell lines. Ascorbate derivatives, which can induce the apoptosis, produced the radical(s), elevated the oxidation potential and stimulated the methionine oxidation in the culture medium, whereas inactive derivatives did not. This suggests that the ascorbate induce the apoptosis by its prooxidant action. The effects of various factors, such as temperature, pH, metal, metal antagonist, redox agent, serum protein, polyphenol and (natural, chemically modified) polysaccharide on the radical intensity and apoptosis-inducing activity of ascorbate are reviewed. Gallate and benzo[a]phenothiazine derivatives, which can induce apoptosis or monocytic differentiation in human myelogenous leukemic cell lines, also produced radicals. These data suggest the significant role of radicals in the initiation of diverse biological activities.

Antineoplastic Agents↗