methyl-13-hydroperoxy-9-11-octadecadienoate and methyl-linoleate

Pyrrolizidine alkaloid (PA)-containing plants are widespread in the world and are probably the most common poisonous plants affecting livestock, wildlife, and human. PAs require metabolic activation to generate pyrrolic metabolites (dehydro-PAs) that bind cellular protein and DNA, leading to hepatotoxicity and genotoxicity, including tumorigenicity. In this study we report that UVA photoirradiation of a series of dehydro-PAs, e.g., dehydromonocrotaline, dehydroriddelliine, dehydroretrorsine, dehydrosenecionine, dehydroseneciphylline, dehydrolasiocarpine, dehydroheliotrine, and dehydroretronecine (DHR) at 0-70 J/cm2 in the presence of a lipid, methyl linoleate, resulted in lipid peroxidation in a light dose-responsive manner. When irradiated in the presence of sodium azide, the level of lipid peroxidation decreased; lipid peroxidation was enhanced when methanol was replaced by deuterated methanol. These results suggest that singlet oxygen is a photo-induced product. When irradiated in the presence of superoxide dismutase, the level of lipid peroxidation decreased, indicating that lipid peroxidation is also mediated by superoxide. Electron spin resonance (ESR) spin trapping studies confirmed that both singlet oxygen and superoxide anion radical were formed during photoirradiation. These results indicate that UVA photoirradiation of dehydro-PAs generates reactive oxygen species (ROS) that mediated the initiation of lipid peroxidation. UVA irradiation of the parent PAs and other PA metabolites, including PA N-oxides, under similar experimental conditions did not produce lipid peroxidation. It is known that PAs induce skin cancer and are secondary (hepatogenous) photosensitization agents. Our results suggest that dehydro-PAs are the active metabolites responsible for skin cancer formation and PA-induced secondary photosensitization.

Topics: Carcinogens; Deuterium; Electron Spin Resonance Spectroscopy; Glutathione; Indicators and Reagents; Kinetics; Linoleic Acids; Lipid Peroxides; Methanol; Pyrrolizidine Alkaloids; Reactive Oxygen Species; Singlet Oxygen; Sodium Azide; Solvents; Spin Trapping; Superoxide Dismutase; Superoxides; Ultraviolet Rays

The stability of plant oils is related to the level of polyunsaturated fatty acids and the presence of native antioxidants--especially tocopherols. During storage, lipids or the fat products undergo oxidation and tocopherol dimers and trimers are formed. These compounds possess reducing and antioxidant properties and participate in oxidation clearly inhibiting this process. In the present study, the correlation between levels of peroxides formed during autoxidation of methyl linoleate and simultaneous decomposition of tocopherols was examined. The peroxide value was investigated. Quantities of decomposed tocopherols and formation of their dimers were determined by high-performance liquid chromatography (HPLC). Mass spectrum analysis confirmed thatthe analysed compounds were dimes. Dimerisation of gamma-T begins at the smaller quantity of the methyl linoleate peroxides than dimerisation of delta-T. At the beginning of methyl linoleate autoxidation dimerisation of gamma-T in relation to its loss was smaller. The quantity of gamma-T dimers with ether bonds in total dimers pointed to faster binding of phenoxy radicals than transformation into the phenyl ones. delta-T dimers with phenyl bonds constitute about 65% of the total. The quantity of peroxides in methyl linoleate, necessary for quantitative and qualitative changes of homologous tocopherols, decreased from delta-T to alpha-T.

Topics: Antioxidants; Chromatography, High Pressure Liquid; Dimerization; Linoleic Acids; Lipid Peroxides; Mass Spectrometry; Oxidation-Reduction; Plant Oils; Tocopherols

alpha-Tocopherol and methyl (9Z,11E)-(S)-13-hydroperoxy-9,11-octadecadienoate (13-MeLOOH) were allowed to stand at 100 degrees C in bulk phase. The products were isolated and identified as methyl 13-hydroxyoctadecadienoate (1), stereoisomers of methyl 9,11,13-octadecatrienoate (2), methyl 13-oxo-9,11-octadecadienoate (3), epoxy dimers of methyl linoleate with an ether bond (4), a mixture of methyl (E)-12,13-epoxy-9-(alpha-tocopheroxy)-10-octadecenoates and methyl (E)-12,13-epoxy-11-(alpha-tocopheroxy)-9-octadecenoates (5), a mixture of methyl 9-(alpha-tocopheroxy)-10,12-octadecadienoates and methyl 13-(alpha-tocopheroxy)-9,11-octadecadienoates (6), alpha-tocopherol spirodiene dimer (7), and alpha-tocopherol trimer (8). alpha-Tocopherol and 13-MeLOOH were dissolved in methyl myristate, and the thermal decomposition rate and the distributions of reaction products formed from alpha-tocopherol and 13-MeLOOH were analyzed. alpha-Tocopherol disappeared during the first 20 min, and the main products of alpha-tocopherol were 5 and 6 with the accumulation of 1-4 which were the products of 13-MeLOOH. The results indicate that the alkyl and alkoxyl radicals from the thermal decomposition of 13-MeLOOH could be trapped by alpha-tocopherol to produce 5 and 6. The reaction products of alpha-tocopherol during the thermal oxidation of methyl linoleate were compounds 6 and 7. Since the radical flux during the autoxidation might be low, the excess alpha-tocopheroxyl radical reacted with each other to form 7.

Topics: Chromatography, High Pressure Liquid; Dimerization; Drug Stability; Free Radicals; Hot Temperature; Kinetics; Linoleic Acids; Lipid Peroxides; Oxidation-Reduction; Stereoisomerism; Vitamin E

The breakdown of methyllinoleate hydroperoxide (LOOH) and peroxidation of methyllinoleate (LH) catalyzed by hemin and hematin were studied in 98% methanol. Spectrophotometry was used to follow the breakdown of LOOH. The peroxidation process of LH was monitored by the oxygen consumption. The pKa for the conversion of hemin to hematin was determined as 7.3 in 98% methanol. The catalytic rates for both processes were found to reach a maximum at pH 8 where about 80% of hemin was in the hematin form. This could be accounted for by the acceleration of the breakdown of LOOH due to binding of hydroxide or methoxide ion to the hemin iron. The reduction in the catalytic activity at a higher pH, where 100% of hemin was in the hematin form, however, suggested that H+ was also necessary. We propose a new scheme which shows the role of H+ and OH- (or CH3O-) together with ferryl iron in the catalytic process. The breakdown of hemin itself was also observed and its catalytic cycle number was estimated as 9. The gradual decomposition of hemin suggests involvement of a Fenton-type mechanism as a minor catalytic process.

Topics: Buffers; Catalysis; Hemin; Hydrogen-Ion Concentration; Linoleic Acids; Lipid Peroxidation; Lipid Peroxides; Methanol; Oxygen Consumption; Porphyrins; Solvents; Spectrophotometry, Ultraviolet

Formation of N-nitrosodimethylamine in chloroform or in mixtures of chloroform/citrate buffer or methyl stearate-chloroform (1:9)/citrate buffer was faster than that in citrate buffer alone. The chemically inert non-aqueous solvent may increase the level of the non-ionized active species of the nitrosating agent. The presence of unsaturated fatty acid methyl esters in chloroform suppressed formation of N-nitrosodimethylamine compared to that in chloroform alone but, because of the non-aqueous solvent effect, nitrosamine formation was slightly higher than that in citrate buffer. Fats containing unsaturated fatty acids also inhibited nitrosamine formation in chloroform indicating that the unsaturated fatty acid residues were effective scavengers of the nitrosating agent. Methyl linoleate was converted into peroxide(s) with carbonyl or carbonyl-liberating functions by reaction with nitrous acid, although it is not clear whether the reaction was relevant to the loss of nitrous acid.

Topics: Chemical Phenomena; Chemistry; Chloroform; Chromatography, Thin Layer; Dimethylnitrosamine; Fatty Acids, Unsaturated; Linoleic Acids; Lipid Peroxides; Nitrosamines; Nitrous Acid; Peroxides; Solvents; Thiobarbiturates

Methyl linoleate hydroperoxide (MLHP) and native methyl linoleate (ML) were tested for carcinogenicity toward the gastrointestinal (GI) tract in male specific-pathogen-free outbred Wistar rats. N-Methyl-N-nitro-N-nitrosoguanidine (MNNG) was given in the drinking water in a dose of 20 mg/liter when cocarcinogenic properties of the test substances were to be tested. MLHP and ML were fed by stomach tube and had no effect as complete carcinogens. Given concomitantly with MNNG, ML did not enhance carcinogenesis. MLHP in conjunction with MNNG was the only treatment which, as treatment with MNNG in a dose of 83 mg/liter, led to an increase of GI cancers in animals that died before day 354. Cumulative results after a maximum of 612 days showed a distribution of GI cancers in favor of the glandular stomach only after MLHP was given with MNNG.

Topics: Animals; Body Weight; Cocarcinogenesis; Gastrointestinal Neoplasms; Intubation, Gastrointestinal; Linoleic Acids; Lipid Peroxides; Male; Methylnitronitrosoguanidine; Rats; Stomach Neoplasms; Time Factors

Linoleate hydroperoxide and linoleate at concentrations of 100-140 nmol-mg protein activated state 4 respiration of rat heart mitochondria 4.2-fold, increased the apparent enthalpy change of the respiration per gram atom of oxygen consumed from -148 to -226 kJ/O and completely inhibited oxidative phosphorylation. Methyl linoleate hydroperoxide or methyl linoleate did not show the same effects. Further addition of linoleate hydroperoxide or linoleate induced oligomycin-insensitive Mg-ATPase to a level 5 or 2 times, respectively, that obtained with 120 muM dinitrophenol, accompanied by clearing of the mitochondrial suspension and release of malate dehydrogenase from the matrix. Methyl linoleate hydroperoxide had the same effects except that the induced Mg-ATPase activity retained oligomycin sensitivity. Methyl linoleate did not show either effect.

Topics: Adenosine Triphosphatases; Animals; Calorimetry; Dose-Response Relationship, Drug; Enzyme Activation; Linoleic Acids; Lipid Peroxides; Magnesium; Male; Mitochondria, Heart; Oxidative Phosphorylation; Oxygen Consumption; Rats