Miki Niikawa

Isolation of substances from glossy privet (Ligustrum lucidum Ait.) inhibiting the mutagenicity of benzo[a]pyrene in bacteria

Methanol and hot-water extracts of glossy privet (Ligustrum lucidum Ait.) inhibited the mutagenic activity of benzo[a]pyrene in Salmonella typhimurium TA98 with S9 mix. The methanol extract was fractionated with ether and n-hexane. As the active components, oleanolic and ursolic acids were isolated, which were soluble in ether and insoluble in n-hexane. The hot-water extract was fractionated to water, 60% and 100% methanol fractions. Nuezhenide was isolated from the 60% methanol fraction as the active component.

Investigation of the hemolytic effects of various organophosphoric acid triesters (OPEs) and their structure‐activity relationship

The hemolytic effects of various organophosphonc acid triesters (OPEs) were investigated and they showed strong hemolyic toxicity except triethyl phosphate and tris(chloroethyl)phosphate. 2‐Ethylhexyl diphenyl phosphate (EHDP) showed the strongest toxicity. By quantitative structure‐activity relationship (QSAR) study, one‐parameter regression equation to estimate hemolysis was not obtained. But, two‐parameter regression equations were obtained which were enought to estimate EC50 and EC20. The correlation coefficients with the two‐parameter regression equations were 0.939 for log(l/EC50) and 0.946 for log(l/EC20).

Augmentation of allergic reactions by several pesticides

The augmentative effects of several pesticides on histamine release from mast cells of rats that had been sensitized passively by anti-dinitrophenol (DNP) monoclonal IgE antibodies were investigated in vitro. Various pesticides, especially phenthoate (PAP), chlornitrofen (CNP) and paraquat (PQ), increased histamine release. This increase was not observed in histamine release with non-antigen or induction by calcium ionophore A23187 or compound 48/80. Passive cutaneous anaphylaxis (PCA) was examined, and an increase of PCA was observed with PAP and PQ, but not with CNP, while an increase of tumor necrosis factor-alpha (TNF-alpha) production was observed with CNP and PQ, but not PAP. These results suggest that various pesticides as environmental pollutants exacerbate allergic diseases.

Stainless‐Steel Ball‐Milling Method for Hydro‐/Deutero‐genation using H2O/D2O as a Hydrogen/Deuterium Source

A one-pot continuous-flow method for hydrogen (deuterium) generation and subsequent hydrogenation (deuterogenation) was developed using a stainless-steel (SUS304)-mediated ball-milling approach. SUS304, especially zero-valent Cr and Ni as constituents of the SUS304, and mechanochemical processing played crucial roles in the development of the reactions.

Relationship between Hemolytic Toxicity and Signal Intensity of Various Organotin Compounds by a Spin‐labeling Technique

Various organotin compounds caused strong hemolysis of erythrocytes. To investigate the mechanism of hemolysis, spin-labeling techniques with electron spin resonance (ESR) spectroscopy were used and the relationship between hemolytic toxicity and signal intensity was investigated. Two kinds of spin-labeled stearic acid in which the paramagnetic center was located at different sites on the alkyl chain (5- and 12-doxyl-stearic acids; 5- and 12-NS) were used. It became clear that the decrease of ESR signal intensity was related to the hemolytic toxicity of the organotin compounds.

Effect of Cotreatment of Aspirin Metabolites on Mitomycin C-Induced Genotoxicity Using the Somatic Mutation and Recombination Test in Drosophila melanogaster

In our previous reports, aspirin, an antipyretic analgesic, suppressed the genotoxicity of mitomycin C (MMC) in a somatic mutation and recombination test (SMART) in Drosophila melanogaster. In order to reveal the mechanism of the anti-genotoxicity of aspirin, we evaluated the suppressing ability of each aspirin metabolite, such as salicylic acid (SA), salicyluric acid (SUA), gentisic acid (GA), gentisuric acid (GUA), and 2,3-dihydroxybenzoic acid (DHBA), in SMART in Drosophila melanogaster using the cotreatment protocol in this report. SUA, GA, GUA, and DHBA reduced the number of the three types of spot induced by MMC without decrease of survival. These aspirin metabolites decreased the genotoxicity frequency of MMC for total spots in a dose-dependent manner. Furthermore, each metabolite decreased the genotoxicity frequency of MMC by approximately 80% at a dose of 40 mg/bottle, respectively. It is suggested that these metabolites are the main substances of anti-genotoxicity in the aspirin metabolic pathway.

Stainless Steel-Mediated Hydrogen Generation from Alkanes and Diethyl Ether and Its Application for Arene Reduction

Hydrogen gas can be generated from simple alkanes (e.g., n-pentane, n-hexane, etc.) and diethyl ether (Et2O) by mechanochemical energy using a planetary ball mill (SUS304, Fritsch Pulverisette 7), and the use of stainless steel balls and vessel is an important factor to generate the hydrogen. The reduction of organic compounds was also accomplished using the in-situ-generated hydrogen. While the use of pentane as the hydrogen source facilitated the reduction of the olefin moieties, the arene reduction could proceed using Et2O. Within the components (Fe, Cr, Ni, etc.) of the stainless steel, Cr was the metal factor for the hydrogen generation from the alkanes and Et2O, and Ni metal played the role of the hydrogenation catalyst.