Nitrite as regulator of hypoxic signaling in mammalian physiology.

In this review we consider the effects of endogenous and pharmacological levels of nitrite under conditions of hypoxia. In humans, the nitrite anion has long been considered as metastable intermediate in the oxidation of nitric oxide radicals to the stable metabolite nitrate. This oxidation cascade was thought to be irreversible under physiological conditions.

Ubichromanol: a prodrug to support mitochondrial ubiquinone functions?

Ubichromanol-9 (UCa9), with a side chain consisting of nine isoprene units) is a reductive cyclization product of ubiquinone-10 (UQ10). It acts as a radical scavenging antioxidant and is about half as effective as alpha-tocopherol. Already decades ago its one-electron oxidation product, the ubichromanoxyl radical had been identified.

The oxidative response in the chronic constriction injury model of neuropathic pain.

Background: In the chronic constriction injury model of rat neuropathic pain, oxidative stress as well as antioxidants superoxide dismutase and reduced glutathione (GSH) are important determinants of neuropathological and behavioral consequences. Studies of the chronic constriction injury model observed (indirect) signs of inflammation. We, therefore, investigated the level of oxidative stress and antioxidant enzymes in skeletal muscle tissue of the rat hind paw and (jugular vein) plasma at d 7 after nerve injury.

Lipid hydroperoxides from processed dietary oils enhance growth of hepatocarcinoma cells.

Linoleic acid, one of the major fatty acid in dietary oils, is an important source for hydroperoxides that may be formed in the presence of oxygen during food processing. Oxidized oils are absorbed in the intestine, transported as chylomicrones to the liver, and may affect unaltered hepatic cells as well as the process of hepatocarcinogenesis. We have studied the effects of linoleic acid hydroperoxides (LOOH) on growth and gene expression of cultured human hepatocellular carcinoma cells (HCC-1.

Cytotoxicity of the novel spin trapping compound 5-ethoxycarbonyl-3,5-dimethyl-pyrroline N-oxide (3,5-EDPO) and its derivatives.

ESR spin trapping allows detection of superoxide radicals. Novel spin traps forming more stable superoxide adducts (t(1/2) ca. 12-55 min) were tested for their toxicity to cultured cells.

Influence of cryopreservation on mitochondrial functions in equine spermatozoa.

Cryopreservation of spermatozoa is of essential importance for artificial insemination and breeding programs in horses. Besides other factors, spermatozoal motility depends on mitochondrial energy metabolism. Based on changes of single mitochondrial functions it has been suggested that mitochondrial damage during cryopreservation could be a major reason for diminished post thaw semen quality.

Free radical trapping properties of several ethyl-substituted derivatives of 5-ethoxycarbonyl-5-methyl-1-pyrroline N-oxide (EMPO).

The spin trapping behavior of several ethyl-substituted EMPO derivatives, cis- and trans-5-ethoxycarbonyl-3-ethyl-5-methyl-pyrroline N-oxide (3,5-EEMPO), 5-ethoxycarbonyl-4-ethyl-5-methyl-pyrroline N-oxide (4,5-EEMPO), cis- and trans-5-ethoxycarbonyl-5-ethyl-3-methyl-pyrroline N-oxide (5,3-EEMPO), and 5-ethoxycarbonyl-5-ethyl-4-methyl-pyrroline N-oxide (5,4-EEMPO), toward a series of different oxygen- and carbon-centered radicals, is described. Considerably different stabilities of the superoxide adducts (ranging from about 12 to 55 min) as well as the formation of other radical adducts were observed.

Opposite effects of endotoxin on mitochondrial and endoplasmic reticulum functions.

In this study, we determined functional integrity and reactive oxygen species generation in mitochondria and endoplasmic reticulum in liver of rats subjected to endotoxic shock to clarify whether intracellular reactive oxygen species (ROS) destabilize cellular integrity causing necrosis in rats challenged with lipopolysaccharide (LPS). LPS caused drastically increased plasma levels of alanine aminotransferase, suggesting damage to plasma membranes of liver cells. Liver necrosis was confirmed by histological examination.

Activation of PPAR-delta in isolated rat skeletal muscle switches fuel preference from glucose to fatty acids.

Aims/hypothesis: GW501516, an agonist of peroxisome proliferator-activated receptor-delta (PPAR-delta), increases lipid combustion and exerts antidiabetic action in animals, effects which are attributed mainly to direct effects on skeletal muscle. We explored such actions further in isolated rat skeletal muscle.

Materials And Methods: Specimens of rat skeletal muscle were pretreated with GW501516 (0.

Ubiquinol and the papaverine derivative caroverine prevent the expression of tumour- promoting factors in adenoma and carcinoma colon cancer cells induced by dietary fat.

High consumption of dietary fat promotes colon carcinogenesis. While this effect is well known the underlying mechanism is not understood. Fatty acid hydroperoxides (LOOH) arise from unsaturated fatty acids in the presence of oxygen and elevated temperature during food processing.

Distribution of tocopheryl quinone in mitochondrial membranes and interference with ubiquinone-mediated electron transfer.

Alpha-tocopherol (Toc) is an efficient lipophilic antioxidant present in all mammalian lipid membranes. This chromanol is metabolized by two different pathways: excessive dietary Toc is degraded in the liver by side chain oxidation, and Toc acting as antioxidant is partially degraded to alpha-tocopheryl quinone (TQ). The latter process and the similarity between TQ and ubiquinone (UQ) prompted us to study the distribution of TQ in rat liver mitochondrial membranes and the interference of TQ with the activity of mitochondrial and microsomal redox enzymes interacting with UQ.

Are the biological properties of kaempferol determined by its oxidation products?

Although flavonoid molecules have attracted considerable interest in recent years because of their antioxidant effect, there are considerable differences in their chemical properties. Electron paramagnetic resonance (EPR) spectroscopy was used to compare the oxidative free radical chemistry of two such molecules, kaempferol and luteolin, which have the same empirical formula but differ in the position of one OH group. Whereas the basic flavonoid structure remains intact in luteolin, structural changes occur in kaempferol after one-electron oxidation.

Different effects of endotoxic shock on the respiratory function of liver and heart mitochondria in rats.

This study was designed to clarify whether mitochondrial function/dysfunction and reactive oxygen species (ROS) production have a temporal relationship with organ failure during endotoxic shock. Adult male Sprague-Dawley rats were divided into three groups receiving 1) isotonic saline (control group, n = 16); 2) 8 mg/kg lipopolysaccharide (LPS; n = 8); or 3) 20 mg/kg LPS (n = 8) intraperitoneally under short anesthesia with 3.5% of isoflurane.

Spin trapping of C- and O-centered radicals with methyl-, ethyl-, pentyl-, and phenyl-substituted EMPO derivatives.

In order to develop spin traps with an optimal ratio between hydrophilic and lipophilic properties, low toxicity, and high stability of spin adducts (especially with superoxide radicals), several EMPO-derived spin traps have recently been synthesized forming more stable superoxide adducts (t(1/2) > 20 min) than DMPO or DEPMPO. In this study, ESR-, 1H-, and 13C-NMR data of several phenyl- or n-pentyl-substituted EMPO derivatives are presented with full signal assignment. Methyl groups at position 3 or 4 stabilized the superoxide adducts considerably.

The existence and significance of a mitochondrial nitrite reductase.

The physiological functions of nitric oxide (NO) are well established. The finding that the endothelium-derived relaxing factor (EDRF) is NO was totally unexpected. It was shown that NO is a reaction product of an enzymatically catalyzed, overall, 5-electron oxidation of guanidinium nitrogen from L-arginine followed by the release of the free radical species NO.

Combination of iron overload plus ethanol and ischemia alone give rise to the same endogenous free iron pool.

Iron overload aggravates tissue damage caused by ischemia and ethanol intoxication. The underlying mechanisms of this phenomenon are not yet clear. To clarify these mechanisms we followed free iron ("loosely" bound redox-active iron) concentration in livers from rats subjected to experimental iron overload, acute ethanol intoxication, and ex vivo warm ischemia.

Cytotoxicity of novel derivatives of the spin trap EMPO.

Free radicals are involved in different regulatory and pathological processes. The formation of superoxide in living cells or whole organisms is of major interest. ESR spin trapping allows identification of the radicals if proper spin traps are available.

Lysosomal ROS formation.

Ubiquinone is inhomogenously distributed in subcellular biomembranes. Apart from mitochondria, where ubiquinone has bioenergetic and pathophysiological functions, unusually high levels of ubiquinone have also been reported in Golgi vesicles and lysosomes. In lysosomes, the interior differs from other organelles in its low pH value which is important to ensure optimal activity of hydrolytic enzymes.

Release and hemodynamic influence of nitro-glycerine-derived nitric oxide in endotoxemic rats.

Background And Aim: Nitric oxide released from nitro-glycerine (NG) has been considered to improve the microcirculation. Septic conditions are, however, associated with excessive formation of nitric oxide (NO), which is formed from l-arginine by the inducible NO synthase (iNOS) activity. Since the characteristics and influence of NG-derived NO in sepsis remains unclear, the major aims of the present study were to quantify the release and to determine the effects of NO formed from NG on systemic blood pressure under endotoxemic conditions.

The protection of bioenergetic functions in mitochondria by new synthetic chromanols.

alpha-Tocopherol is the most important lipophilic antioxidant of the chromanol type protecting biomembranes from lipid peroxidation (LPO). Therefore, alpha-tocopherol and its derivatives are frequently used in the therapy or prevention of oxygen radical-derived diseases. In the present study, novel chromanol-type antioxidants (twin-chromanol, cis- and trans-oxachromanol) as well as the well-known short-chain analogue of alpha-tocopherol, pentamethyl-chromanol, were tested for their antioxidative potency in rat heart mitochondria (RHM).

Suppression of tumour-promoting factors in fat-induced colon carcinogenesis by the antioxidants caroverine and ubiquinone.

Fatty acid hydroperoxides are produced from unsaturated fatty acids in the presence of oxygen at elevated temperatures during food processing. Their effects on gene expression in colorectal tumour cells were studied using linoleic acid hydroperoxide (LOOH) as a model compound. Addition of LOOH to the medium of LT97 adenoma and SW480 carcinoma cells enhanced the production of hydrogen peroxide.

Skeletal muscles, heart, and lung are the main sources of oxygen radicals in old rats.

The aim of this study was to compare rat tissues with respect to their reactive oxygen and nitrogen species (RONS) generating activities as a function of age. We quantified the RONS generation in vivo in young (6 months) and in old (30 months) male Sprague-Dawley rats using the recently developed spin trap 1-hydroxy-3-carboxy-pyrrolidine, applied intravenously. This spin trap reacts with superoxide radical and peroxynitrite yielding a stable spin adduct which is detectable by means of electron paramagnetic resonance (EPR) spectroscopy in frozen tissues.

Very stable superoxide radical adducts of 5-ethoxycarbonyl- 3,5-dimethyl-pyrroline N-oxide (3,5-EDPO) and its derivatives.

Oxygen radicals are involved in the onset of many diseases. Adequate spin traps are required for identification and localisation of free radical formation in biological systems. Superoxide spin adducts with half-lives up to 20 min at physiological pH have recently been reported to be formed from derivatives of the spin trap 5-ethoxycarbonyl-5-methyl-1-pyrroline N-oxide (EMPO).

Antioxidant, prooxidant and cytotoxic activity of hydroxylated resveratrol analogues: structure-activity relationship.

Resveratrol (trans-3,4',5-trihydroxystilbene), a naturally occurring hydroxystilbene, is considered an essential antioxidative constituent of red wine possessing chemopreventive properties. However, resveratrol and even more its metabolite piceatannol were reported to have also cytostatic activities. In order to find out whether this is related to antioxidative properties of those compounds, we synthesized five other polyhydroxylated resveratrol analogues and studied structure-activity relationships between pro-/antioxidant properties and cytotoxicity.