Epoxide Residue Research Articles

Identification of Paracentrone in Fucoxanthin-Fed Mice and Anti-Inflammatory Effect against Lipopolysaccharide-Stimulated Macrophages and Adipocytes.

Fucoxanthin is converted to fucoxanthinol and amarouciaxanthin A in the mouse body. However, further metabolism such as cleavage products (i.e., apocarotenoids) remains unclear. The fucoxanthin-derived apocarotenoid in vivo is investigated and the anti-inflammatory effect of apocarotenoids with fucoxanthin partial structure such as allenic bond and epoxide residue against activated macrophages and adipocytes in vitro is evaluated. LC-MS analysis indicates the presence of paracentrone, a C31 -allenic-apocarotenoid, in white adipose tissue of diabetic/obese KK-Ay and normal C57BL/6J mice fed 0.2% fucoxanthin diet for 1 week. In lipopolysaccharide-activated RAW264.7 macrophages, paracentrone as well as C26 - and C28 -allenic-apocarotenoids suppresses the overexpression of inflammatory factors. Further, apo-10'-fucoxanthinal, a fucoxanthin-derived apocarotenoid which retained epoxide residue, exhibits a most potent anti-inflammatory activity through regulating mitogen-activated protein kinases and nuclear factor-κB inflammatory signal pathways. In contrast, β-apo-8'-carotenal without allenic bond and epoxide residue lacks suppressed inflammation. In 3T3-L1 adipocytes, paracentrone, and apo-10'-fucoxanthinal downregulate the mRNA expression of proinflammatory mediators and chemokines induced by co-culture with RAW264.7 cells. Dietary fucoxanthin accumulates as paracentrone as well as fucoxanthinol and amarouciaxanthin A in the mouse body. Allenic bond and epoxide residue of fucoxanthin-derived apocarotenoids have pivotal roles for anti-inflammatory action against activated macrophages and adipocytes.

Parthenolide induces a distinct pattern of oxidative stress in cardiac myocytes

Although parthenolide was reported to reduce cardiovascular damage in endotoxic shock and have beneficial effects in myocardial ischemia, its actions on cardiac myocytes have not been reported. Because parthenolide possesses an α-methylene-γ-lactone ring and epoxide residue, we hypothesized that it would induce oxidative stress in cardiac myocytes. Superoxide production and sources, viability, glutathione levels, and mitochondrial membrane potential were studied in neonatal rat ventricular myocytes treated with parthenolide. Parthenolide, dose dependently, induced oxidase activity as assessed by superoxide generation in cell lysates. Superoxide formation was increased more than 4-fold with 50 μM parthenolide. At concentrations > 5 μM, parthenolide decreased cell viability in a dose-and time-dependent manner, and activated the stress MAP kinases JNK and p38. Over 6 h, parthenolide at concentrations > 5 μM markedly depleted intracellular glutathione and led to collapse of the mitochondrial membrane potential. At lower parthenolide concentrations (< 5 μM) the source of superoxide was mitochondria; at higher concentrations (> 5 μM) the primary source was NADPH oxidase. We conclude that parthenolide causes oxidative stress in cardiac myocytes by inducing superoxide formation by mitochondrial and NADPH oxidase in a dose-dependent manner. Parthenolide may be a useful tool for studying the roles of oxidative stress and mitochondrial dysfunction in the pathogenesis of cardiac hypertrophy and failure.

DNA binding and alkylation by the "left half" of azinomycin B.

Azinomycin B (also known as carzinophilin A) contains two electrophilic functional groups-an epoxide and an aziridine residue-that react with nucleophilic sites in duplex DNA to form cross-links at 5'-dGNT and 5'-dGNC sequences. Although the aziridine residue of azinomycin is undoubtedly required for cross-link formation, analogues containing an intact epoxide group but no aziridine residue retain significant biological activity. Azinomycin epoxide analogues (e.g., 5 and 6) are of interest due to their potent biological activity and because there is evidence that azinomycin may decompose in vivo to yield such compounds. To investigate the chemical events underlying the toxicity of azinomycin epoxides, DNA binding and alkylation by synthetic analogues of azinomycin B (6, 8, and 9) that comprise the naphthalene-containing "left half" of the antibiotic have been investigated. The epoxide-containing analogue of azinomycin (6) efficiently alkylates guanosine residues in duplex DNA. DNA alkylation by 6 is facilitated by noncovalent binding of the compound to the double helix. The results of UV-vis absorbance, fluorescence spectroscopy, DNA winding, viscometry, and equilibrium dialysis experiments indicate that the naphthalene group of azinomycin binds to DNA via intercalation. Equilibrium dialysis experiments provide an estimated binding constant of (1.3 +/- 0.3) x 10(3) M(-)(1) for the association of a nonalkylating azinomycin analogue (9) with duplex DNA. The DNA-binding and alkylating properties of the azinomycin epoxide 6 provide a basis for understanding the cytotoxicity of azinomycin analogues which contain an epoxide residue but no aziridine group and may provide insight into the mechanisms by which azinomycin forms interstrand DNA cross-links.

A novel tetracyclic peptide, trapoxin, induces phenotypic change from transformed to normal in sis-oncogene-transformed NIH3T3 cells.

A novel tetra cyclic peptide, trapoxin [cyclo(L‐phenylalanyl‐L‐phenylalanyl‐D‐pipecolinyl‐L‐2‐amino‐8‐oxo‐9,10‐epoxy‐decanoyl)], was found to induce the flat phenotype in v‐sis‐transformed NIH3T3 cells at a quite low concentration of 1 ng/ml. Actin stress fiber could be detected after trapoxin treatment. Almost complete reversion into the flat phenotype was observed at 6 h after the administration of the compound. The effect of trapoxin was reversible, when the cell culture was incubated for more than 24 h after its removal. The intracellular level of sis‐mRNA did not decrease with trapoxin treatment at a concentration (50 ng/ml), sufficient to reverse the transformed morphology. Substitution of pipecolinic acid with proline in trapoxin did not change the activity. WF3161, in which leucine was substituted for a phenylalanine of trapoxin, showed only one‐sixteenth of the activity of trapoxin. Reduction of the epoxide residue of trapoxin destroyed the activity.

Analogs of cell surface carbohydrates. Synthesis of d-galactose derivatives having an ethynyl, vinyl or epoxy residue at C-5

Compounds derived from d-galactose having an ethynyl, vinyl, or epoxide residue at C-5, as well as 7,7-dibromo olefinic, isomeric 7,7- gem-bromofluoro olefinic, and 6,6- gem-difluoro derivatives were obtained from 1,2:3,4-di- O-isopropylidene-α- d- galacto-hexodialdo-1,5-pyranose.

Changes in pattern of organochlorine residues in blood of general Israeli population, 1975–1986

This study reviews data on the changes with time of the blood levels of some organochlorine compounds (OCCs) in the general Israeli population. All the studied OCC residues, except for p, p′-DDD, were significantly lower in 1985–1986 than in 1975. A decline in blood residues of organochlorine pesticides was observed mainly in the second half of the 1970s, whereas a fall in the polychlorinated biphenyl residue levels took place in the first half of the 1980s. During the latter period, unexplained increases in p, p′-DDD, dieldrin and heptachlor epoxide residue levels were seen. A significant decrease in the blood levels of OCCs quickly metabolized in the body ( p, p′-DDT, tetrachlorobiphenyls) indicated a considerable reduction of environmental exposures. The clear decline in OCC contamination of the environment and, in particular, of the human body during the reviewed period (1975–1986) resulted from the restriction imposed in Israel on the use of OCCs. Nevertheless this does not mean that this problem has been solved. Some health implications of low-level life-long OCC exposure are discussed, and further environmental and biological monitoring and control measures are recommended.

Selective ethylene oxide hydrolysis catalysed by oxo-molybdenum species

Ortho-molybdate and ortho-tungstate (MO 2− 4, M = Mo or W) are selective catalysts for the hydrolysis of ethylene oxide. Model compounds synthesized from epoxides and organic soluble molybdate and tungstate salts of the bis(triphenylphosphine)iminium cation suggest that intermediates in this reaction are anionic molybdenum(VI) or tungsten(VI) alkoxide complexes of type [MO 2(OCH 2CH 2O) 2] 2−, containing chelating vicinal dialkoxide ligands derived from the epoxide residue. Hydrolysis of an ethylene oxide derived complex has been shown to yield exclusively monoethylene glycol as the organic product, with the regeneration of the metallate dianion (MO 2− 4).

New polyketide metabolites from Aspergillus melleus: structural and stereochemical studies

The structures of two new fungal products asperlactone (5) and isoasperlactone (6) have been deduced by comparison of their spectroscopic data with that of aspyrone (3), a known co-metabolite. All three compounds have been degraded by ozonolysis to produce crystalline derivatives of 2,3-epoxybutyric acid (9) and 1-methylglycerol (11). From measurements of optical activity it has been established that aspyrone and isopasperlactone have the (5S,6R,8S,9S) configuration, whereas that of asperlactone is (5R,6S,8S,9S). The relative stereochemistry of aspyrone has been checked by an X-ray crystallographic study: [P212121, a= 4.427(3), b= 14.272(3), c= 14.968(3)A, Z= 4, R= 0.033 for 1 131 unique observed reflections]. The stereochemical relationships are discussed in terms of a biosynthetic proposal by which (3) and (5) would be biosynthesised from a common intermediate via alternative cyclisations of a carboxy group onto an epoxide residue. It is possible that (6) is a chemical artefact derived from (3).

Residues of organochlorine pesticides in broilers from feed fortified with known levels of these compounds

Abstractp, p'‐DDT, HEOD, endrin, heptachlor epoxide, hexachlorobenzene and lindane were fed in combination to day‐old broiler chickens at levels of 0.05, 0.15 and 0.30 part/million in the feed, for a period of about 7 weeks. Birds were killed at regular intervals and samples of abdominal fat and other tissues examined for residues of the chlorinated pesticides by gas‐liquid chromatography. The lipid content of each sample was determined and the residue levels calculated for the whole tissue and also for the fat contained in the sample.At the end of the 7 weeks (when in practice broilers are slaughtered) residues were highest for heptachlor epoxide, followed by hexachlorobenzene, HEOD, DDT (total), endrin, and lindane. Heptachlor epoxide residue levels in fat were 13 times the levels in the feed, for lindane the ratio was 3.3. Fat residues of each pesticide reached a plateau level relatively quickly, and these levels were proportional to the fortification rates in the feed. HEOD and p, p'‐DDT alone were fed to separate groups of birds. No differences in residue build‐up of these compounds were found between these groups and the groups that had received these compounds in combination with the other pesticides.The total amounts of each pesticide in the tissues were reduced when the meat was fried, probably by loss of fat during preparation and frying. For p, p'‐DDT and heptachlor epoxide also smaller residue were observed in the remaining fat after frying.

The Effect of Humidity on the Volatilization of Certain Insecticides

Reports on studies of humidity effects on residue life of insecticides are meager. Kalkat et al. (1961) pointed out fumigant action of some insecticides increased significantly under similar temperature conditions when their residues were tested at 80 ± 5% RH in comparison with similar residues tested at 55 ± 5% RH. Under high humidity there was a rapid change of insecticide into the vapor phase and in amounts high enough to account for fumigant effect. They showed also that loss of heptachlor epoxide residue was 2 times greater at the high humidity.