Biomedical subjects

G Spiteller

Publications and source records attributed to G Spiteller.

At least 37 records · Page 2Linked to original sources

PubMed1997

2-Hydroxy-succinaldehyde, a lipid peroxidation product proving that polyunsaturated fatty acids are able to react with three molecules of oxygen.

2-Hydroxy-succinaldehyde was detected by a GC/MS analysis of trapped aldehydic compounds obtained after Fe2+/ascorbate lipid peroxidation of arachidonic acid. Precursor molecules of aldehydes are hydroperoxy compounds. Thus the generation of the two aldehydic groups in 2-hydroxysuccinaldehyde requires a precursor molecule with two hydroperoxy groups. The hydroxy group in 2-position is generated by a third hydroperoxidation reaction. The detection of 2-hydroxysuccinaldehyde--although found only in traces--is the first example for triple dioxigenation of unsaturated fatty acid. Linolenic acid produces 2-hydroxysuccinaldehyde in much lower amounts than arachidonic acid. A similar oxidation of linoleic acid was not observed.

Aldehydes↗

PubMed1996

Increase in hydroxy fatty acids in human low density lipoproteins with age.

The content of hydroxy fatty acids in low density lipoprotein (LDL) of healthy volunteers aged between 22 and 87 years without any signs of atherosclerosis or other age-dependent diseases was investigated. The level of hydroxy fatty acids obtained from LDL increases during life time: clinically healthy persons between 56 and 66 years showed a 3- to 4-fold increase compared to young volunteers. This level increased in samples of probands aged 68 to 74 years compared to samples of young people for a factor of 10-20 and in samples of probands aged 78 to 87 years for a factor of 30-40. These hydroxy acids--generated mainly from hydroperoxy acids on linoleic acid and only partly from arachidonic acid--are obviously parameters of the LDL oxidation stage. About 90% of the total amount of hydroxy fatty acid were free fatty acids. The distribution patterns of the monohydroxy derivatives of linoleic and arachidonic acid indicate that they originate mainly from autocatalytic processes. The individual level of hydroxy acids is probably an indicator of the biological age.

Adult↗

PubMed1996

Increase of aldehydic compounds derived from plasmalogens in the brain of aged cattle.

The content of plasmalogens in bovine brain was investigated with respect to age. No difference between the plasmalogen content in brain of young and old individuals was detected. In old individuals, plasmalogens suffer much easier hydrolysis to corresponding aldehydes than in young ones. In addition, the brain of old animals contain an approx. 30-fold higher amount of free aldehydes and plasmalogen epoxides compared to young ones. Aldehydes, as well as derived alpha-hydroxyaldehydes, were trapped by addition of pentafluorobenzylaminehydrochloride. The resulting pentafluorobenzyloxime derivatives were enriched by thin-layer chromatography, transferred to trimethylsilyl derivatives and further investigated by GC/MS. Quantification was achieved by GC/FID as well as by GC/ECD.

Aging↗

PubMed1996

Lipid oxidation products in ischemic porcine heart tissue.

Infarcted porcine heart tissue and surrounding tissue were investigated for the content of plasmalogens and oxidatively derived corresponding alpha-hydroxyaldehydes as well as for products of lipid peroxidation, e.g. malondialdehyde, glyoxal, 2-hydroxyheptanal and oxygenated fatty acids. Oxidation products of unsaturated fatty acids and plasmalogens were accumulated in infarcted tissue compared to the surrounding one. Their amounts increased with time of ischemia. In addition leukotoxins (9, 10-epoxy-12-octadecenoic acid and 12,13-epoxy-9-octadecenoic acid) as well as other epoxides of unsaturated fatty acids were identified. These compounds are absent in healthy heart tissue. Some of the monohydroxy fatty acids, found in comparable high yield, can not be derived from LPO processes. They are obviously generated from epoxides. Their distribution pattern indicates that they originate by an enzymic rather than by an autocatalytic process. We assume that the enzymes are activated by cell injury due to infarction. Linoleic acid seems to be an as equally well-suited substrate for enzymic attack as arachidonic acid.

Aldehydes↗

PubMed1996

Plasmalogens and their oxidative degradation products in low and high density lipoprotein.

The kinetics of the autoxidation reaction of LDL and HDL with Fe2+/ascorbate was investigated. Aldehydes derived from plasmalogens were determined by conversion to 2-alkyl-1,3-dithiolanes. Their oxidation products, 2-hydroxy-aldehydes, were trapped by reaction with pentafluorobenzylhydroxylamine. After derivatisation, the pentafluorobenzyloximes could be separated from other compounds by thin-layer chromatograpy. They were detected by gas chromatography applying an electron capture detector. LDL plasmalogens are oxidized nearly completely after 180 min while HDL plasmalogens suffer oxidation only to 5%. Oxidation of linoleic and arachidonic acid was investigated by simultaneous determination of 2-hydroxyheptanal.

Animals↗

PubMed1996

Enzymatic production of hydroperoxides of unsaturated fatty acids by injury of mammalian cells.

Hydroperoxides of unsaturated fatty acids (LOOHs) are generated by homogenisation of liver tissue, but not if the liver is boiled before homogenisation. This observation indicates that the LOOHs are produced in an enzymatic reaction. This assumption is corroborated by an analysis of the reduction products of LOOHs by gas chromatography/mass spectrometry (GC/MS). A main part of LOOHs is derived from linoleic acid and not from arachidonic acid. Massive cell damage occurs by myocardial infarction or other severe injuries; these events were found to be connected with generation of LOOHs. We suspect--considering the above outlined experiment--that the LOOH production is also mainly caused in these cases by activation of enzymes and not--as postulated--by an autocatalytic process. Increased amounts of LOOHs are found in many chronic diseases, e.g. in rheuma, atherosclerosis or psoriasis, obviously caused by a gradual damage of cells. Thus, the common root of an increased LOOH level might be cell injury.

Aldehydes↗

PubMed1996

Previously unknown aldehydic lipid peroxidation compounds of arachidonic acid.

Arachidonic acid was oxidized by iron ascorbate. Samples were withdrawn in time intervals. The aldehydic oxidation products were trapped by preparation of pentafluorbenzyloximes. Their trimethylsilylated derivatives were subjected to analysis by GC/MS. The main aldehydic lipid peroxidation product was found to be the well-known 4-hydroxy-2-nonenal (HNE), but 2-hydroxy heptanal (HH) -- a previously unknown lipid peroxidation product of arachidonic acid -- was detected to be nearly equally abundant. Malondialdehyde (MDA), glyoxal and 2-hydroxy-4-decenal (HDE) were detected to be produced in up to 100 times lower amounts compared to HNE. The amounts of aldehydes increased steadily with time. In addition, n-l-hydroxy-n-oxo acids were detected. Similar aldehydes were obtained by iron ascorbate-induced oxidation of hydroxy acids derived by NaBH4-reduction of 13-hydroperoxy-9-cis-11-trans-octadecadienoic acid. Since this and analogous hydroxy acids (LOHs) are the main biological degradation products of hydroperoxides of unsaturated acids (LOOHs) their further peroxidation seems to be a main source of toxic aldehydes.

Acetamides↗

PubMed1996

Enzymic lipid peroxidation--a consequence of cell injury?

It is postulated that cell injury activates "dormant" enzymes to produce lipid hydroperoxides. In a first step, membrane lipids are cleaved by esterases. The unsaturated fatty acids thus produced are converted in a second step by lipoxygenases to lipid hydroperoxides (LOOHs). In a third, nonenzymic step, these LOOHs, together with dienoic hydroxy fatty acids produced by enzymic reduction of LOOHs, react with a second oxygen molecule to generate dihydroperoxy-fatty acids and hydroxy-hydroperoxy-fatty acids, which are degraded to alpha-hydroxyladehydic compounds. This last reaction requires production of LO'-radicals by iron ions that also are generated as a result of cell damage. In addition, alpha-hydroxyaldehydes are produced by hydrolysis of plasmalogen epoxides, which are generated by oxidation of plasmalogens with LOO' or by action of epoxidases. We hypothize that alpha-hydroxyaldehydes act as second messengers. The release of lipoxygenase and the consequent lipid hydroperoxidation is postulated to occur in massive cell damage (e.g., myocardial infarction), in chronic diseases such as rheumatism, diabetes and atherosclerosis, in aging, and in control of cell proliferation.

Aging↗

PubMed1996

Iron (II) ions induced oxidation of ascorbic acid and glucose.

Lipid peroxidation (LPO) of polyunsaturated fatty acids (PUFAs) is suspected to be involved in the generation of chronic diseases. A model reaction for LPO is the air oxidation of PUFAs initiated by Fe2+ and ascorbic acid. In the course of such model reactions glycolaldehyde (GLA) was detected as main aldehydic product. Since it is difficult to explain the generat on of GLA by oxidation of PUFAs, it was suspected that GLA might be derived by oxidation of ascorbic acid. This assumption was verified by treatment of ascorbic acid with Fe2+. Produced aldehydic compounds were trapped by addition of pentafluorobenzylhydroxylamine hydrochloride (PFBHA-HCl), trimethylsilylated and finally identified by gas chromatography/mass spectronetry (GC/MS). Oxidation of ascorbic acid with O2 in presence of iron ions produced not only glycolaldehyde (GLA), but also glyceraldehyde (GA), dihydroxyacetone (DA) and formaldehyde. Glyoxal (GO) and malondialdehyde (MDA) were detected as trace compounds. The yield of the aldehydic compounds was increased by addition of lipid hydroperoxides (LOOH) or H2O2. The buffer influenced the reaction considerably: Iron ions react with Tris buffer by producing dihydroxyacetone (DA). Since ascorbic acid is present in biological systems and Fe2+ ions are obviously generated by cell damaging processes, the production of GLA and other aldehydic components might add to the damaging effects of LPO. Glucose suffers also oxidation to short-chain aldehydic compounds in aqueous solution, but this reaction requires addition of equimolar amounts of Fe2+ together with equimolar amounts of H2O2 or 13-hydroperoxy -9-cis-11-trans-octadecadienoic acid (13-HPODE). Therefore this reaction, also influenced by the buffer system, seems to be not of biological relevance.

Aldehydes↗

PubMed1995

Gas chromatographic-electron impact mass spectrometric screening procedure for unknown hydroxyaldehydic lipid peroxidation products after pentafluorobenzyloxime derivatization.

Aldehydic lipid peroxidation products can be detected after transformation to pentafluorobenzyloxime derivatives by GC-MS screening using characteristic ion traces. Thus the rather unstable unsaturated hydroxyaldehyde, 6-hydroxy-2,4-undecadienal, was identified as autoxidation product of linoleic acid. Its structure was unambiguously confirmed by comparison with an authentic sample. After Fe(2+)-ascorbate induced lipid peroxidation of oleic acid several 4-hydroxy-2-alkenals and 4-hydroxyalkanals were detected. These represent previously unknown secondary oxidation products of lipid peroxidation of oleic acid. Nevertheless oleic acid proved about 1000 times more stable against peroxidation than linoleic or higher unsaturated acids.

Aldehydes↗

PubMed1995

Detection of short-chain alpha-hydroxyaldehydic compounds as pentafluorbenzyloxime derivatives in bovine liver.

Pentafluorbenzyloxime derivatization allows fast, gentle and unambiguous identification of alpha-hydroxyaldehydic lipid peroxidation products via GC/MS in biological material. Even 1.5 g of a bovine liver sample is sufficient to detect short-chain 2-hydroxyalkanales resulting from cleavage reactions of dioxygenated fatty acids. Quantification is achieved after secondary derivatization with N-methyl-N-t-butyldimethylsilyltrifluoracetamide (M-t-BSTFA) by mass spectrometry using characteristic ion traces of the derivatives. In addition, the corresponding (n-1)-hydroxy-n-oxo acids, previously unknown in biological material, could be detected.

Acetamides↗

PubMed1995

Epoxidation of plasmalogens: source for long-chain alpha-hydroxyaldehydes in subcellular fractions of bovine liver.

1. Masked long-chain alpha-hydroxyaldehydes were trapped in all subcellular fractions of bovine liver by application of pentafluorbenzyloxime derivatization [van Kuijk, Thomas, Stephens and Dratz (1986) Biochem. Biophys. Res. Commun. 139, 144-149] and quantified via GLC/MS using characteristic ion traces. 2. The chain-length profile of long-chain 2-hydroxyalkanales clearly indicates their relationship to plasmalogens as precursor molecules. 3. The previously postulated existence of alpha-acyloxyplasmalogens as precursor molecules of masked long-chain alpha-hydroxyaldehydes in bovine tissue lipids [Lutz and Spiteller (1991) Liebigs Ann. Chem. 1991, 563-567] was excluded. 4. The constant oxidation rate of plasmalogens in all subcellular fractions provides conclusive evidence for a non-enzymic plasmalogen epoxidation process (probably via hydroperoxy radicals). 5. The high reactivity of alpha-hydroxyaldehydes sheds some doubt on the postulation that plasmalogens protect mammalian cells against oxidative stress as postulated previously [Morand, Zoeller and Raetz (1988) J. Biol. Chem. 263, 11590-11596; Morand, Zoeller and Raetz (1988) J. Biol. Chem. 263, 11597-11606].

Aldehydes↗

PubMed1995

Plasmalogen oxidation in human serum lipoproteins.

The content of plasmalogens in lipoproteins--very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL)--in human serum was determined and compared with that after oxidation of the lipoproteins. Similarly, the content of alpha-hydroxyaldehydes produced from plasmalogens via their epoxids during lipidperoxidation (LPO) was studied. Incubation with Fe+ +/ascorbate results in a dramatic decrease in plasmalogens that correlates with an appropriate increase in alpha-hydroxyaldehydes. VLDL and LDL plasmalogens were oxidized to a greater extend (99% decrease) compared to HDL plasmalogens (35%). This finding is discussed with respect to atherogenesis and the recently postulated protective qualities of plasmalogens.

Aldehydes↗

PubMed1995

Methylation of the beta-positions of the furan ring in F-acids.

Major incubation products in feeding experiments with the sodium salt of 7-(5-butyl-furan-2-yl)heptanoic acid (3) on suspension cultures of Saccharum spec. are the unusual F-acids (4a) and (4b). They possess in contrast to natural monomethyl substituted F-acids a methyl substituent in the 4-position of the furan ring. Unexpectedly, the dimethyl substituted F-acids (4c) and (4d) were found only in very small amounts. The detection and structure elucidation of the methylation products (4a)-(4d) was achieved predominantly by GC-MS analysis of the corresponding tetrahydrofuran derivatives (5a)-(5d).

Cells, Cultured↗

PubMed1995

[Cell damage as reason for the formation of unsaturated fatty acid hydroperoxides].

In diseases leading to massive acute cell damage, e.g., myocardial infarction or spontaneous inflammation, increased amounts of hydroperoxides of unsaturated fatty acids (LOOH) are found. An even higher production of LOOH is observed in homogenized tissue. If cells are injured, dormant lipoxygenases (LOX) are inevitably activated. They oxidize unsaturated membrane fatty acids to LOOH. This process involves not only arachidonic acid - as tacitly assumed up to now - but also linoleic acid. LOOH are decomposed to chemically highly reactive species, some of which were previously unknown (e.g, alpha-hydroxyaldehydes). LOO. radicals can also transform any molecule with a double bond to an epoxide. Therefore, epoxides are found in injured tissue. The same degradation products of hydroperoxides have been observed in elevated amounts in acute cell injury and in chronic diseases, e.g., atherosclerosis, psoriasis, and rheumatoid diseases. Therefore, we conclude that in these cases too, increased generation of hydroperoxides is caused by gradual cell injury liberating lipoxygenases.

Animals↗

PubMed1994

Reinvestigation of lipid peroxidation of linolenic acid.

Recently, we deduced a mechanism for lipid peroxidation of linoleic acid [1]. This mechanism was now applied to predict the occurrence of previously unknown lipid peroxidation products of linolenic acid. The proposed structures of peroxidation products allowed to search for these predicted compounds in reaction mixtures with the aid of 'ion trace' by mass spectrometry. Thus, a great number of previously unknown lipid peroxidation products was detected. It is assumed that these compounds also occur--at least as intermediates--in lipid peroxidation processes in mammalian tissue.

Gas Chromatography-Mass Spectrometry↗

PubMed1994

Generation of alpha-hydroxyaldehydic compounds in the course of lipid peroxidation.

Based on 18O-labeling experiments a general scheme for the generation of hydroxy aldehydic compounds in the course of lipid peroxidation of linoleic acid is developed. Key intermediates are obviously dioxygenated fatty acids, since after reduction with either NaBH4 or Rh/H2 1.2 and 1.6 dihydroxy fatty acids can be identified. The postulated mechanism not only explains the formation of 2-hydroxyalkanals but also supports earlier hypothesis concerning the generation of 4-hydroxyalkenals. In addition it predicted the occurrence of (n - 1)-hydroxy-n-oxo fatty acids as additional oxidation products. A search for these previously unknown autoxidation products of linoleic acid was indeed successful.

Aldehydes↗

PubMed1994

Oxidation of furan fatty acids by soybean lipoxygenase-1 in the presence of linoleic acid.

The interaction of furan fatty acids (F-acids) with lipoxygenase was investigated by incubation experiments of a synthetic dialkyl-substituted F-acid with soybean lipoxygenase-1. Originally the oxidation of furan fatty acids was assumed to be directly effected by lipoxygenase. It is now demonstrated that this reaction is a two-step process that requires the presence of lipoxygenase substrates, e.g. linoleic acid. In the first step linoleic acid is converted by the enzyme to the corresponding hydroperoxide. This attacks, probably in a radical reaction, the furan fatty acid to produce a dioxoene compound that can be detected unequivocally by gas chromatography-mass spectrometry.

Fatty Acids↗