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Biomedical subjects

G Spiteller

Publications and source records attributed to G Spiteller.

At least 19 recordsLinked to original sources
PubMed2002

Oxidized products of linoleic acid stimulate adrenal steroidogenesis.

Adrenal steroidogenesis is under complex control, and clinical observations suggest that not all regulators have been identified. We postulated that fatty acid oxidation products found in the diet or formed in the body could affect steroidogenesis. Linoleic acid is a prominent constituent of animal fat and is readily oxidized. We found that several products of linoleic acid oxidation affect production of aldosterone and corticosterone by isolated cells from rat adrenals. We characterized one linoleic acid derivative by gas chromatography/mass spectrometry. It is 12,13-epoxy-9-oxo-10(trans)-octadecenoic acid ("EKODE"). At concentrations between 1 and 30 microM, EKODE stimulated production of aldosterone by zona glomerulosa cells, but at concentrations above 50 microM, it was inhibitory. In zona fasciculata cells, EKODE stimulated corticosterone production at concentrations of 5 microM or greater, and there was no evidence of inhibition at high concentrations. Stimulation of steroidogenesis was observed after 15 min of incubation and continued for at least 2 hrs. The potential relevance of our findings to the hypertension of obesity is discussed.

Aldosterone↗
PubMed2001

Peroxidation of linoleic acid and its relation to aging and age dependent diseases.

Cell proliferation, cell injury and aging are connected with changes in the cell membrane structure. Apparently these changes activate, in mammalian as well as in plant cells, lipases which liberate polyunsaturated fatty acids (PUFAs). PUFAs are the substrates for lipoxygenases which convert them to corresponding hydroperoxides (LOOHs). Lipoxygenases commit suicide by releasing iron ions. LOOHs react with iron ions to generate radicals. Thus, a nonenzymic lipid peroxidation process (LPO) is induced. It is speculated that the change from enzymic to nonenzymic LPO is connected with the switch from apoptosis to necrosis and that LOOHs produced in enzymic reactions are degraded specifically to signal compounds which induce physiological responses, while nonenzymic reactions seem to induce generation of reactive oxygen species, cell death and age related diseases. Enzymic and nonenzymic LPO processes concern all PUFAs not only arachidonic acid. The main PUFA in mammals is linoleic acid. Since these products serve signalling functions, different degradation paths of linoleic-hydroperoxides are described in detail and the physiological properties of LPO products are discussed in relation to aging and age related diseases.

Aging↗
PubMed2001

Aldehydic lipid peroxidation products derived from linoleic acid.

Lipid peroxidation (LPO) processes observed in diseases connected with inflammation involve mainly linoleic acid. Its primary LPO products, 9-hydroperoxy-10,12-octadecadienoic acid (9-HPODE) and 13-hydroperoxy-9,11-octadecadienoic acid (13-HPODE), decompose in multistep degradation reactions. These reactions were investigated in model studies: decomposition of either 9-HPODE or 13-HPODE by Fe(2+) catalyzed air oxidation generates (with the exception of corresponding hydroxy and oxo derivatives) identical products in often nearly equal amounts, pointing to a common intermediate. Pairs of carbonyl compounds were recognized by reacting the oxidation mixtures with pentafluorobenzylhydroxylamine. Even if a pure lipid hydroperoxide is subjected to decomposition a great variety of products is generated, since primary products suffer further transformations. Therefore pure primarily decomposition products of HPODEs were exposed to stirring in air with or without addition of iron ions. Thus we observed that primary products containing the structural element R-CH=CH-CH=CH-CH=O add water and then they are cleaved by retroaldol reactions. 2,4-Decadienal is degraded in the absence of iron ions to 2-butenal, hexanal and 5-oxodecanal. Small amounts of buten-1,4-dial were also detected. Addition of m-chloroperbenzoic acid transforms 2,4-decadienal to 4-hydroxy-2-nonenal. 4,5-Epoxy-2-decenal, synthetically available by treatment of 2,4-decadienal with dimethyldioxirane, is hydrolyzed to 4,5-dihydroxy-2-decenal.

Air↗
PubMed2001

Ceramide-epoxides.

Previously unknown 4,5-epoxy-N-acetyl-sphingosine (1) was synthesized by epoxidation of N-acetyl-sphingosine with 1,1-dimethyldioxirane. A by-product generated by HPLC purification is the tetrahydrofuryl derivative of acetamide (2). Mainly allylic oxidation was observed when natural ceramides were reacted with dimethyldioxirane.

Ceramides↗
PubMed2001

Lipid peroxidation in aging and age-dependent diseases.

Aging is related with an increase in oxidation products derived from nucleic acids, sugars, sterols and lipids. Evidence will be presented that these different oxidation products are generated by processes induced by changes in the cell membrane structure (CMS), and not by superoxide, as commonly assumed. CMS activate apparently membrane bound phospholipases A2 in mammals and plants. Such changes occur by proliferation, aging and especially by wounding. After activation of phospholipases, influx of Ca2+ ions and activation of lipoxygenases (LOX) is induced. The LOX transform polyunsaturated fatty acids (PUFAs) into lipid hydroperoxides (LOOHs), which seem to be decomposed by action of enzymes to signalling compounds. Following severe cell injury, LOX commit suicide. Their suicide liberates iron ions that induce nonenzymic lipid peroxidation (LPO) processes by generation of radicals. Radicals attack all compounds with the structural element -CH=CH-CH(2)-CH=CH-. Thus, they act on all PUFAs independently either in free or conjugated form. The most abundant LPO products are derived from linoleic acid. Radicals induce generation of peroxyl radicals, which oxidise a great variety of biological compounds including proteins and nucleic acids. Nonenzymic LPO processes are induced artificially by the treatment of pure PUFAs with bivalent metal ions. The products are separable after appropriate derivatisation by gas chromatography (GC). They are identified by electron impact mass spectrometry (EI/MS). The complete spectrum of LPO products obtained by artificial LPO of linoleic acid is detectable after wounding of tissue, in aged individuals and in patients suffering from age-dependent diseases. Genesis of different LPO products derived from linoleic acid will be discussed in detail. Some of the LPO products are of high chemical reactivity and therefore escape detection in biological surrounding. For instance, epoxides and highly unsaturated aldehydic compounds that apparently induce apoptosis.

Aging↗
PubMed2000

Oxidation of Linoleic Acid in Low-Density Lipoprotein: An Important Event in Atherogenesis.

Contrary to earlier views the main oxidation products of low-density lipoprotein (LDL) are derived from linoleic acid and not arachidonic acid, as determined by GC/MS investigations of the in vitro oxidation of LDL samples. A similar product spectrum, in which epoxyhydroxyoctadecenoic acids such as 1 and 2 have been identified for the first time, is obtained from minimally oxidized (that is, aged) LDL. Since this is still recognized by the LDL receptor, it is concluded that toxic oxidation products are introduced in endothelial cells in vivo and cause damage there.

Journal Article↗
PubMed2000

Synthesis of 9,12-dioxo-10(Z)-dodecenoic acid, a new fatty acid metabolite derived from 9-hydroperoxy-10,12-octadecadienoic acid in lentil seed (Lens culinaris Medik.)

The previously unknown linoleic acid peroxidation product 9,12-dioxo-10(Z)-decenoic acid (Z5) was detected in lentil seed flour (Lens culinaris Medik.) by electron impact mass spectrometry (EI-MS) after derivatization with pentafluorobenzyl-hydroxylamine-hydrochloride, methylation of acidic groups with diazomethane, and protection of hydroxylic groups with N-methyl-N-trimethylsilyl-trifluoroacetamide. The structure of the natural product was confirmed by synthesis of Z5, 9,12-dioxo-l0(E)-decenoic acid, and derivatives. EI-MS, nuclear magnetic resonance and gas chromatographic data of these compounds and synthetic intermediates are discussed.

Chromatography, Gas↗
PubMed1999

The reaction of hyaluronic acid and its monomers, glucuronic acid and N-acetylglucosamine, with reactive oxygen species.

Synovial fluid is a approximately 0.15% (w/v) aqueous solution of hyaluronic acid (HA), a polysaccharide consisting of alternating units of GlcA and GlcNAc. In synovial fluid of patients suffering from rheumatoid arthritis, HA is thought to be degraded either by radicals generated by Fenton chemistry (Fe2+/H2O2) or by NaOCl generated by myeloperoxidase. We investigated the course of model reactions of these two reactants in physiological buffer with HA, and with the corresponding monomers GlcA and GlcNAc. meso-Tartaric acid, arabinuronic acid, arabinaric acid and glucaric acid were identified by GC-MS as oxidation products of glucuronic acid. When GlcNAc was oxidised, erythronic acid, arabinonic acid, 2-acetamido-2-deoxy-gluconic acid, glyceric acid, erythrose and arabinose were formed. NaOCl oxidation of HA yielded meso-tartaric acid; in addition, arabinaric acid and glucaric acid were obtained by oxidation with Fe2+/H2O2. These results indicate that oxidative degradation of HA proceeds primarily at glucuronic acid residues. meso-Tartaric acid may be a useful biomarker of hyaluronate oxidation since it is produced by both NaOCl and Fenton chemistry.

Acetylglucosamine↗
PubMed1998

Strong dependence of the lipid peroxidation product spectrum whether Fe2+/O2 or Fe3+/O2 is used as oxidant.

Catalytic amounts of Fe2+ or Fe3+ ions are widely applied to induce simulated biological lipid peroxidation reactions. Independently, whether Fe2+ or Fe3+ were used, similar products were obtained. We show in this paper that the product spectrum is indeed very different, whether one ion species, either Fe2+ or Fe3+, is present in excess; thus, decomposition of (13S,9Z,11E) 13-hydroxyperoxy-9, 11-octadecadienoic acid (13S-HPODE) generates in the presence of equimolar amounts of Fe2+ ions mainly the corresponding alcohol (13S, 9Z,11E) 13-hydroxy-9,11-octadecadienoic acid besides 12,13-epoxy-11-hydroxy-9-octadecenoic acid (12,13-epHOD) and 13-oxo-9,11-octa-decadienoic acid (13-KODE), while decomposition of 13S-HPODE with equimolar amounts of Fe3+ produces mainly 12,13-epHOD, hydrolysis products thereof and other oxidized products, e.g., hydroxyoxo acids. In addition, unusually large amounts of aldehydes are formed, e.g., the amount of 4-hydroxy-nonenal was found to exceed that obtained by Fe2+ induced air oxidation for a factor of about 100. Since these further oxidation products are suspected to cause cell damage, liberated Fe3+ ions seem to be responsible for generation of toxic products in inflammatory diseases, e.g., atherosclerosis.

Chromatography, Thin Layer↗
PubMed1998

Strong increase in hydroxy fatty acids derived from linoleic acid in human low density lipoproteins of atherosclerotic patients.

Linoleic acid is the most abundant fatty acid in human low density lipoproteins (LDL). Oxidation of LDL transforms linoleic acid to hydroperoxyderivatives. These are converted to 9-hydroxy-10,12-octadecadienoic acid (9-HODE) and 13-hydroxy-9,11-octadecadienoic acid (13-HODE). 9-HODE is much more abundant in oxidized LDL than other lipid peroxidation products and therefore an indicator of lipid peroxidation (LPO). In this study the 9-HODE content in the LDL of 19 obviously healthy volunteers and 17 atherosclerotic patients was investigated. The level of 9-HODE obtained from LDL of young atherosclerotic patients (aged 36-47 years) was increased by a factor of 20 when compared with samples from healthy volunteers of the same age group. The content of 9-HODE in the LDL of atherosclerotic patients aged between 69 and 94 years increased 30-100 fold when compared with young healthy individuals, but when compared with 'healthy' individuals of the same age group it was only 2-3 fold increased. Obviously, as individuals grow older LDL becomes more and more oxidized. Consequently, assuming that LDL oxidation is a precondition for atherosclerosis--older individuals will suffer from atherosclerosis, even if no easy detectable visible signs of this disease are recognizable. According to 9-HODE determination, the onset of the disease starts slowly in most individuals at around 50 years of age.

Adult↗
PubMed1998

Linoleic acid peroxidation--the dominant lipid peroxidation process in low density lipoprotein--and its relationship to chronic diseases.

Modern separation and identification methods enable detailed insight in lipid peroxidation (LPO) processes. The following deductions can be made: (1) Cell injury activates enzymes: lipoxygenases generate lipid hydroperoxides (LOOHs), proteases liberate Fe ions--these two processes are prerequisites to produce radicals. (2) Radicals attack any activated CH2-group of polyunsaturated fatty acids (PUFAs) with about a similar probability. Since linoleic acid (LA) is the most abundant PUFA in mammals, its LPO products dominate. (3) LOOHs are easily reduced in biological surroundings to corresponding hydroxy acids (LOHs). LOHs derived from LA, hydroxyoctadecadienoic acids (HODEs), surmount other markers of LPO. HODEs are of high physiological relevance. (4) In some diseases characterized by inflammation or cell injury HODEs are present in low density lipoproteins (LDL) at 10-100 higher concentration, compared to LDL from healthy individuals.

Aging↗
PubMed1998

Lignans interfering with 5 alpha-dihydrotestosterone binding to human sex hormone-binding globulin.

The natural lignans (-)-3,4-divanillyltetrahydrofuran (1), (-)-matairesinol (2), (-)-secoisolariciresinol (3), (+/-)-enterolactone (4), (+/-)-enterodiol (5), and nordihydroguaiaretic acid (NDGA) (6) reduce the binding of 3H-labeled 5 alpha-dihydrotestosterone (DHT) to human sex hormone-binding globulin (SHBG). (-)-3,4-Divanillyltetrahydrofuran (1) has the highest binding affinity (Ka = 3.2 +/- 1.7 x 10(6)M-1) of all lignans investigated so far; the reversibility of its binding and a double reciprocal plot suggest a competitive inhibition of the SHBG-DHT interaction. Increasing hydrophobity in the aliphatic part of the lignans (butane-1,4-diol-butanolide-tetrahydrofuran structures) leads to higher binding affinity. In the aromatic part, a 3-methoxy-4-hydroxy substitution pattern is most effective for binding to SHBG.

Charcoal↗
PubMed1997

Dramatic increase of alpha-hydroxyaldehydes derived from plasmalogens in the aged human brain.

Plasmalogens-substantial compounds of brain tissue--suffer degradation either by hydrolysis under production of aldehydes or by oxidation with lipid peroxylradicals by generation of plasmalogen epoxides. The latter react by addition of pentafluorobenzylhydroxylamine HCl (PFBHA HCL) under hydrolysis to alpha-hydroxyaldehydes which are immediately transformed to pentafluorobenzyloximes (PFBO). Likewise, free aldehydes are transformed to PFBO-derivatives. PFBO-derivatives of free aldehydes and PFBO-derivatives of alpha-hydroxyaldehydes were extracted and after trimethylsilylation quantified by GC/FID and by GC/MSD. The remaining aqueous phase, containing plasmalogens besides other lipids, was hydrolyzed by treatment with acid. The hydrolysis products of plasmalogens, long chain aldehydes, react with PFBHA HCl to produce PFBO-derivatives. These were also quantified by GC/FID. This method allows the quantification of plasmalogens, free aldehydes and plasmalogenepoxides in human brain samples to study changes in the relation of these compounds with increasing age. While the ratio of plasmalogens in respect to derived aldehydes seems to remain constant during life time, the quotient of plasmalogenepoxides to plasmalogens increases with age, indicating that lipid peroxidation processes are involved in the damage of plasmalogens in the brain of aged individuals, starting at an age of about 70 years.

Adolescent↗
PubMed1997

Lipid peroxidation in presence of ebselen.

Lipid peroxidation is initiated by cell damage. After homogenisation of porcine heart tissue in aqueous solution we observed the same lipid peroxidation products as detected after heart infarction. We used this observation to study the influence of ebselen (2-phenyl-1,2-benzoisoselenazol-3-(2H)-one) on the generation of oxidatively derived monohydroxy fatty acids and alpha-hydroxyaldehydes, typical lipid peroxidation (LPO) products. Heart tissue was homogenised before and after enzyme destruction and with addition of ebselen. The obtained LPO products were analysed by GC/MS after appropriate derivatisation and quantified by using internal standards. The amount of monohydroxy fatty acids and alpha-hydroxyaldehydes increased considerably in the porcine heart homogenates in which the enzymes were kept active. Addition of ebselen caused an additional significant increase of hydroxy fatty acids, while the increase of aldehydic compounds was less. These results confirm the glutathione peroxidase-like activity of ebselen but demonstrate also that it does not prevent lipid peroxidation.

Acetamides↗
PubMed1997

Increased levels of lipid oxidation products in low density lipoproteins of patients suffering from rheumatoid arthritis.

9-Hydroxy-10,12-octadecadienoic acid (9-HODE) and 13-hydroxy-9,11-octadecadienoic acid (13-HODE) are accumulated in the low density lipoproteins of patients suffering from rheumatoid arthritis for a factor of 20-50 compared to healthy individuals of the same age. Both acids, derived by lipid peroxidation of linoleic acid, induce the release of interleukin 1 beta. The latter induces bone degression. The genesis of 9- and 13-HODE seems therefore to be an important factor in the development and progression of rheuma; in addition 9-HODE was reported to be a stimulus of inflammation, comparable to leukotrienes.

Adult↗
PubMed1997

Lignans from the roots of Urtica dioica and their metabolites bind to human sex hormone binding globulin (SHBG).

Polar extracts of the stinging nettle (Urtica dioica L.) roots contain the ligans (+)-neoolivil, (-)-secoisolariciresinol, dehydrodiconiferyl alcohol, isolariciresinol, pinoresinol, and 3,4-divanillyltetrahydrofuran. These compounds were either isolated from Urtica roots, or obtained semisynthetically. Their affinity to human sex hormone binding globulin (SHBG) was tested in an in vitro assay. In addition, the main intestinal transformation products of plant lignans in humans, enterodiol and enterolactone, together with enterofuran were checked for their activity. All lignans except (-)-pinoresinol developed a binding affinity to SHBG in the in vitro assay. The affinity of (-)-3,4-divanillyltetrahydrofuran was outstandingly high. These findings are discussed with respect to potential beneficial effects of plant lignans on benign prostatic hyperplasia (BPH).

Humans↗