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Biomedical subjects

K Satoh

Publications and source records attributed to K Satoh.

At least 1,315 records · Page 73Linked to original sources

Quantitative evaluation of pulmonary ventilation dynamics using MR imaging: comparison of smokers and non-smokers.

PURPOSE: This quantitative study was conducted to evaluate lobar ventilation dynamics in non-smokers and smokers using MR imaging. METHODS: Ten non-smoker males and ten smoker males underwent MR imaging in the supine position without breath-holding. The volume rates and fluctuation rates were calculated for each lobe from MR images. TVRCs were constructed and analyzed. RESULTS: In non-smokers, the mean volume rates for each lung and lobe arranged in order of diminishing values were RL (54.8%), LL (45.2%), RLL (25.9%), LUL (24.2%), LLL (21.0%), RUL (18.5%), and RML (10.3%). In smokers, the mean volume rates for each lung and lobe arranged in order of diminishing values were RL (55.7%), LL (44.3%), RLL (25.1%), LUL (24.0%), RUL (21.0%), LLL (19.9%), and RML (9.5%). In both groups, there was a tendency for the fluctuation rates of the lower lobes to be higher than those of the upper and middle lobes. Although TVRCs for the right and left lung were nearly parallel, with no time lag, the peaks of TVRCs for the upper and middle lobes appeared slightly earlier than those for the lower lobes. CONCLUSION: The evaluation of pulmonary ventilation dynamics using MR may be a useful non-invasive technique by which to assess lung lobar ventilation.

Adult↗

Antitumor activity of benzo[a]phenothiazines.

We have previously reported on the diverse biological activities of benzo[a]phenothiazines, such as the induction of antitumor and antimutagenic activity in vivo, and differentiation and apoptosis in vitro. The relationship of radical generation and pi-spin density or dipole moment was investigated, using quantum-chemical calculation with UHF/PM3. These data suggest that the origin of radical generation by active benzo[a]phenothiazines, which affect such biological activities might be N-atom at position 12.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Radical intensity and cytotoxicity of butylated hydroxyanisole and its orthobisphenol dimer.

The radical intensity of BHA (4-Hydroxy-3-t-butylanisole) and its dimer (3,3'-Di-t-butyl-5,5'-dimethoxy-1,1'-biphenyl-2,2'-diol, Bis-BHA) were compared with their cytotoxic activity. ESR spectroscopy showed that BHA produced characteristic five peaks of radicals under alkaline conditions (pH > 9.5). At higher pH, BHA radical rapidly disappeared, and progressively transformed into new radical species, as detected by the splitting of the ESR signal. BHA showed higher cytotoxic activity against salivary gland tumor cell line than against normal human gingival fibroblast. On the other hand, Bis-BHA did not produce any detectable amounts of radicals at wide ranges of pH, corresponding with its weaker cytotoxic activity as compared with BHA. BHA scavenged DPPH (1,1-Diphenyl-2-picrylhydrazyl) radical and superoxide anion, more efficiently than Bis-BHA. The present study demonstrated that BHA is more cytotoxic, produces higher amounts of radicals and more efficiently scavenges various radical species, as compared with Bis-BHA. This suggests the possible link between the cytotoxic activity and radical generation/scavenging activity in BHA-derived compounds.

Antioxidants↗

Interaction between sodium ascorbate and polyphenols.

The interaction between sodium ascorbate and polyphenols was investigated by two different parameters: radical intensity and cytotoxicity induction. ESR spectroscopy shows that sodium ascorbate, lignins (alkali-lignin, lignin sulfonate, pine cone-derived lignin) and tannins (gallic acid, epigallocatechin gallate (EGCg), tannic acid) all produced radicals with different intensities under alkaline conditions. All lignin samples significantly enhanced the radical intensity and cytotoxic activity of sodium ascorbate, whereas all tannin samples slightly reduced the radical intensity of sodium ascorbate. Sodium ascorbate efficiently scavenged the radical and cytotoxic activity of gallic acid, as expected by the ionization potential and heat of reaction by the PM3 semiempirical method. EGCg and tannic acid slightly reduced the cytotoxic activity of sodium ascorbate. The present study demonstrates that lignins and tannins modify the radical intensity and cytotoxic activity of sodium ascorbate in different manners, and suggests the applicability of ESR spectroscopy for the screening of drug to drug interaction.

Ascorbic Acid↗

Interaction between antioxidants and hydroquinone/bisphenol.

We have investigated the stability of semiquinone radical (SQ .) produced from the mixture of hydroquinone (HQ) and bisphenol A (BPA) in the presence of various antioxidants, some of which induce apoptosis in tumor cell lines. BPA produced no detectable amount of ESR signal. The acceleration of HQ oxidation by BPA results in the production of SQ .. The BPA-enhanced SQ . production may occur through either SQ. regeneration by electron transfer from BPA working as an antioxidant or the O2- scavenging activity of BPA. SQ . intensity of HQ/BPA was reduced by lower concentrations of sodium ascorbate, epigallocatechin, gallate and quercetin, but significantly enhanced by gallic acid. The initial SQ . was replaced by the radicals of antioxidants except lignin and salicylic acid, at higher concentrations, due to their radical-radical coupling or dismutation process. Among these compounds, gallic acid enhanced the radical intensity of SQ . to the greatest extent. The results suggest that antioxidants from foods suppress the activity of xenobiotics such as HQ, however, they produce their own radical at higher concentrations, suggesting their bimodal actions. The present study demonstrates the usefulness of ESR spectroscopy for the interaction between HQ/BPA and antioxidants.

Antioxidants↗

Measurement of protein C inhibitor in seminal plasma is useful for detecting agenesis of seminal vesicles or the vas deferens.

Protein C inhibitor (PCI), a plasma serine protease inhibitor of activated protein C, is present at high concentrations in the seminal plasma of normal subjects and is decreased in some infertile patients. We measured the concentrations of PCI, prostate-specific antigen, and fructose in the seminal plasma of infertile patients (n = 125) and of normal subjects (n = 13). We also measured time-dependent changes in the concentrations of PCI and fructose in seminal plasma after ejaculation. A weak correlation was found between the levels of PCI and fructose (r = 0.268, P = 0.016). The PCI level in seminal plasma of patients with seminal vesicle and/or vasal agenesis was significantly lower (P < .01) than in normal subjects. The level of fructose in seminal plasma decreased in vitro in a time-dependent manner after ejaculation, whereas the concentration of PCI was stable at 48 hours after ejaculation. These data suggest that PCI in seminal plasma, as well as fructose, may become one of the markers for agenesis of seminal vesicles and/or the vas deferens.

Enzyme-Linked Immunosorbent Assay↗

Induction of apoptosis by dopamine in human oral tumor cell lines.

Dopamine dose-dependently reduced the viable cell number of both human salivary gland tumor HSG and oral squamous cell carcinoma HSC-2, HSC-4, and NA cells. CoCl2 significantly reduced both the cytotoxic activity and radical intensity of dopamine (determined by ESR spectroscopy). Dopamine produced DNA fragments (demonstrated by TUNEL method) and induced degradation of cytokeratin by activated caspase in HSG cells (detected by an immunocytochemical method, using a specific M30 monoclonal antibody). FACS analysis demonstrated that dopamine induced DNA fragmentation, a biochemical hallmark of apoptosis, in human promyelocytic leukemia HL-60 cells. The addition of catalase did not prevent the apoptosis-inducing activity of dopamine, reducing the possibility of the involvement of H2O2 for dopamine-induced apoptosis. Dopamine transiently induced p38 mitogen-activated protein kinase (MAP kinase) phosphorylation. However, an inhibitor of p38 MAP kinase phosphorylation, SB203680, failed to inhibit the dopamine-induced apoptosis. These data suggest that p38 phosphorylation at an early stage may not be a causative event for apoptosis.

Apoptosis↗

Induction of apoptosis by flavones, flavonols (3-hydroxyflavones) and isoprenoid-substituted flavonoids in human oral tumor cell lines.

Various flavones, flavonols (3-hydroxyflavones) and isoprenoid-substituted flavones (flavonols) were investigated for their cytotoxic activity. Most of these compounds were more cytotoxic against human oral squamous cell carcinoma and salivary gland tumor cell lines than human gingival fibroblasts. The cytotoxic activity of flavonoids was generally higher than that of tannin-related compounds. Flavonoids induced apoptotic cell death characterized by DNA fragmentation (as identified by TUNEL method) and activation of caspase(s) (as identified by degradation products of cytokeratin 18 with M30 monoclonal antibody). ESR spectroscopy revealed that higher concentrations of flavonoids produced radicals under alkaline conditions. However, not all of them enhanced the radical intensity of sodium ascorbate, suggesting that the redox potential of flavonoids differs considerably from samples to samples. Catalase failed to eliminate the cytotoxic activity of flavonoids, reducing the possibility of the involvement of hydrogen peroxide for the cytotoxicity induction by them.

Apoptosis↗

3,5-diacetyl-1,4-dihydropyridines: synthesis and MDR reversal in tumor cells.

Eleven 4-phenyl-3,5-diacetyl-1,4-dihydropyridines (AcDHPs) [G1-11] substituted at the phenyl ring were synthesized and compared for their cytotoxic activity and multidrug resistance (MDR)-reversing activity in in vitro assay systems. Among them, compound [G7] showed the highest cytotoxic activity against human promyelocytic leukemia HL-60 and human squamous cell carcinoma HSC-2 cells. However, no compounds tested produced radicals at pH 7.4-12.5. The activity of P-glycoprotein (Pgp) responsible for MDR in tumor cells was reduced by compounds [G2, 3, 6, 5, 8, 1, 11], verapamil [VP] and nifedipine [NP]. However, compounds [G4, 7, 10] were hardly active while G9 did not show a MDR reversing effect at 2.0-20.0 micrograms/mL. These data show a relationship between chemical structures and MDR-reversing effect on tumor cells.

Antineoplastic Agents↗

Selective cytotoxic activity of grape peel and seed extracts against oral tumor cell lines.

Grape seed extracts were more cytotoxic than grape peel extracts. Methanol and 70% methanol extracts of grape seed selectively killed two human oral tumor cell lines, more efficiently than human gingival fibroblasts. ESR spectroscopy revealed that these extracts produced radicals under alkaline conditions and enhanced the radical intensity of sodium ascorbate at higher concentrations. On the other hand, lower concentration of these extracts slightly reduced the radical intensity of sodium ascorbate, and scavenged superoxide anion, generated by hypoxanthine and xanthine oxidase reaction. These properties of grape seed extracts suggest their possible application for cancer prevention.

Anticarcinogenic Agents↗

Antimicrobial and radical modulation activity of AV-07, a poly-herbal formula.

An extract of AV-07 was investigated for various biological activities. Pretreatment of mice with the AV-07 extract significantly protected them from lethal infection with E. coli. ESR spectroscopy showed that the extract produced radicals under alkaline conditions and enhanced the radical intensity of sodium ascorbate, suggesting its pro-oxidant action at higher concentrations. The extract effectively scavenged superoxide anion, produced by hypoxanthine-xanthine oxidase reaction and hydroxyl radical, produced by Fenton reaction. These data demonstrate that AV-07 extract contains various bioactive substances, suggesting its medicinal efficacy.

Animals↗

Interaction between hydroquinone and ascorbic acid derivatives: quenching effect of organic solvents.

The interaction between hydroquinone (HQ) and ascorbic acid analogs was investigated. Semiquinone radicals (SQ.) generated by HQ were comparably scavenged by ascorbic acid, sodium ascorbate and ascorbate 6-palmitate, but much less efficiently by ascorbate 2,6-dipalmitate. Organic solvents, such as dimethysulfoxide (DMSO) or ethanol, which are utilized for solubilization of water-insoluble analogs, ascorbate 6-palmitate and ascorbate 2,6-dipalmitate, also scavenged SQ.. DMSO scavenged the SQ. more efficiently than ethanol. This suggests the importance of considering such a quenching effect of organic solvent in the study of the interaction between HQ and antioxidants. The involvement of the ascorbate radical for cytotoxicity induction is discussed.

Ascorbic Acid↗

Interaction between chlorogenic acid and antioxidants.

The interaction between chlorogenic acid (CGA) and antioxidants was investigated by two different parameters: radical intensity and cytotoxicity induction. ESR spectroscopy shows that CGA produced radicals under alkaline condition. The CGA radical was scavenged by 100-300-fold lower concentrations of sodium ascorbate or N-acetyl-l-cysteine (NAC), whereas the ascorbate radical was not completely scavenged by CGA. The cytotoxic activity of CGA against human oral tumor cells (HSC-2, HSG) was completely eliminated by lower concentrations of sodium ascorbate or NAC, whereas that of sodium ascorbate or NAC was only slightly reduced by CGA. The present study demonstrated that CGA induces cytotoxicity by its radical-mediated oxidation mechanism and suggests the applicability of ESR spectroscopy for the screening of drug to drug interaction.

Acetylcysteine↗

Cytotoxicity and radical intensity of eugenol, isoeugenol or related dimers.

To investigate the possible link between radicals and cytotoxicity of eugenol-related compounds, dimer compounds were synthesized from eugenol (4-allyl-2-methoxyphenol) or isoeugenol (4-propenyl-2-methoxyphenol): bis-eugenol (3,3'-dimethoxy-5,5'-di-2-propenyl-1,1'-biphenyl-2,2'-diol); dehydrodiisoeugenol (2-(3-methoxy-4-hydroxyphenyl)-3-methyl-5-(1-propenyl)-7-methoxy-2,3- dihydrobenzofuran) and alpha-di-isoeugenol (r-l-ethyl-5-hydroxy-t-3-(4-hydroxy-3-methoxyphenyl)-6-methoxy-c-2- methylindane). Both the cytotoxic activity and the DNA synthesis inhibitory activity of these compounds against a salivary gland tumor cell line (HSG) and normal human gingival fibroblast (HGF) were decreased in the order of: dehydrodiisoeugenol, alpha-di-isoeugenol > isoeugenol > eugenol > bis-eugenol. Electron spin resonance (ESR) spectroscopy showed that dehydrodiisoeugenol, alpha-di-isoeugenol and eugenol, but not isoeugenol and bis-eugenol, produced phenoxyl radicals under alkaline condition (pH > 9.5). However, benzyl radicals were produced during the dimerization of isoeugenol to dehydrodiisoeugenol. The radical intensity of alpha-di- and dehydrodiisoeugenol appeared at relatively later incubation time than eugenol, suggesting that their phenoxyl radical was more stable than that of eugenol. Such a phenoxyl radical is produced by scavenging free radicals, during the inhibition of lipid peroxidation. Higher cytotoxic activity of isoeugenol dimers was thought to be induced by interaction with cell membranes via the lipophilic radical. The present study supports the notion that relative cytotoxicity of chemicals can be evaluated by measuring the radical intensity using ESR.

Antineoplastic Agents↗

Radical modulating activity and cytotoxic activity of synthesized eugenol-related compounds.

The ability of nine synthetic eugenol-related compounds to scavenge O2- (generated by the hypoxanthine-xanthine oxidase reaction) was compared with their radical generation and cytotoxic activity. ESR spectroscopy showed that eugenol (4-allyl-2-methoxyphenol), 2-allyl-4-methoxyphenol, 2-allyl-4-t-butylphenol and 2,4-dimethoxyphenol efficiently scavenged O2- and produced radicals under alkaline conditions. 2-allyl-4-t-butylphenol showed the highest cytotoxic activity and DNA-synthesis inhibitory activity, possibly due to the hydrophobic radical reactivity. 2-allyl-4-methoxyphenol and 2,4-dimethoxyphenol showed higher antioxidant activity than 3-t-butyl-4-hydroxyanisol (BHA), but all these compounds showed comparable cytotoxic activity with each other. These findings suggest a possible link between the cytotoxic activity and radical generation/scavenging activity in eugenol-related compounds.

Antineoplastic Agents↗

Effect of cobalt ion on radical intensity and cytotoxic activity of antioxidants.

The effect of CoCl2 on the cytotoxic activity of various antioxidants against human oral tumor cell lines (HSC-2, HSG) and normal human gingival fibroblasts (HGF) was investigated. Noncytotoxic concentrations of CoCl2 significantly reduced the cytotoxic activity of sodium ascorbate, gallic acid, epigallocatechin gallate (EGCG), curcumin and dopamine, but not that of sodium 5,6-benzylidene-L-ascorbate (SBA) and benzaldehyde. Among these compounds, benzaldehyde showed the most prominent tumor-specific cytotoxic action. ESR spectroscopy showed that these antioxidants produced radicals under alkaline condition and that their radical intensity was transiently enhanced and finally disappeared by addition of CoCl2. Antioxidants which are sensitive to CoCl2 generally had higher cytotoxic activity and oxidation potential (measured by NO monitor) and addition of CoCl2 significantly reduced their oxidation potential. The present study suggests that cobalt ion stimulates the oxidation of antioxidants to their inactive products.

Antioxidants↗

Effect of antioxidants on radical intensity and cytotoxicity of hydroquinone.

Hydroquinone (HQ) dose-dependently reduced the viable cell number of oral tumor cell lines (HSC-2, HSG). HQ induced internucleosomal DNA fragmentation in human promyelocytic leukemic HL-60 cells, but not in HSC-2 nor HSG cells. Cytotoxic activity of HQ was slightly reduced by catalase, but was enhanced by superoxide dismutase, suggesting the possible involvement of hydrogen peroxide in HQ-induced cytotoxicity. This was supported by slight increase or decrease of cytotoxicity of HQ in the presence of Cu2+ and Fe3+, respectively. Lower concentrations of sodium ascorbate, ascorbic acid and ascorbic acid 6-palmitate reduced both the radical intensity and cytotoxic activity of HQ, more efficiently than ascorbic acid 2,6-dipalmitate, in contrast to the cytotoxic action of these ascorbates at higher (millimolar) concentrations. Popular antioxidants such as N-acetyl-L-cysteine and cysteine also reduced the radical intensity and cytotoxic activity of HQ. The present study suggests that cytotoxic activity of HQ is generated by radical-mediated oxidation mechanism.

Antioxidants↗

Cytotoxic activity of steroidal saponins against human oral tumor cell lines.

Three steroidal saponins showed higher cytotoxicity against human oral squamous cell carcinoma cell lines (HSC-2), as compared with normal human gingival fibroblasts HGF. Tumor specificity of saponins exceeded that of tannins and flavonoids. Agarose gel electrophoresis showed that saponins failed to induce internucleosomal DNA fragmentation, but produced large DNA fragments in both HSC-2 cells and human promyelocytic leukemic HL-60 cells. In contrast to epigallocatechin gallate or gallic acid, cytotoxic activity of saponins was not significantly affected by metals (Co2+, Cu2+, Fe3+) nor by antioxidants (sodium ascorbate, N-acetyl-L-cysteine, catalase). Furthermore, saponins did not produce radicals (detected by ESR spectroscopy) nor oxidation potential (measured by NO monitor). These data suggest that an oxidation-mediated mechanism is not involved in the cytotoxicity induced by steroidal saponins.

Antineoplastic Agents↗