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R Reiter

Publications and source records attributed to R Reiter.

At least 55 records · Page 3Linked to original sources
PubMed1989

Subcellular distribution of selenium in deficient mouse liver.

Selenium (Se)-deficient mice were labelled in vivo with single pulses of [75Se]selenite, and the intrahepatic distribution of the trace element was studied by subcellular fractionation. At 1 h after intraperitoneal injection of 3.3 or 10 micrograms of Se/kg body weight, 15% of the respective doses were found in the liver. Accumulation in the subcellular fractions followed the order: Golgi vesicular much greater than lysosomal greater than cytosolic = microsomal greater than mitochondrial, peroxisomal, nuclear and plasma-membrane fraction. At a dose of 3.3 micrograms/kg, more than 90% of the hepatic Se was protein-bound. When cross-contamination was accounted for, the following specific Se contents of the subcellular compartments were extrapolated: Golgi apparatus, 7.50 pmol/mg; cytosol, 0.90 pmol/mg; endoplasmic reticulum, 0.80 pmol/mg; mitochondria, 0.49 pmol/mg; nuclei, lysosomes, peroxisomes and plasma membrane, less than 0.4 pmol/mg. At 10 micrograms/kg, a roughly 2-3-fold increase in Se content of all fractions was found without major changes in the intrahepatic distribution pattern. An extraordinary rise in the cytosolic fraction was due to an apparently non-protein-bound Se pool. At 24 h after dosing, total hepatic Se had decreased to 6% of the initial dose and had become predominantly protein-bound. The 60% decrease in hepatic Se was reflected in a similar fall in the subcellular levels of the trace element. The Golgi apparatus still had the highest specific Se content, although accumulation was 5 times less than that after 1 h. The cytosolic pool accounted for 50% of the hepatic Se at both labelling times. After 1 h the Golgi apparatus was, with 19%, the second largest intrahepatic pool, followed by the endoplasmic reticulum with 16%. The high affinity and fast response of the Golgi apparatus to Se supplementation of deficient mice is interpreted in terms of a predominant function of this cell compartment in the processing and the export of Se-proteins from the liver.

Animals↗
PubMed1988

Formation of glutathione adducts of carbon tetrachloride metabolites in a rat liver microsomal incubation system.

Metabolism of CCl4 by rat liver microsomes causes damage to the membrane. GSH diminishes that damage. One mechanism of GSH protection has been characterized. It involves formation of diglutathione carbonate from two molecules of GSH and one molecule of phosgene, an oxygenated metabolite of CCl4. The present studies were done to seek other GSH adducts of CCl4 metabolites and to examine the effect of oxygen tension on their formation. Incubations were carried out in sealed flasks under oxygen concentrations ranging from 0.14 to 21% at 37 degrees. The CCl4 concentration was 72 microM. 14CCl4 and 35S-GSH were used to label metabolites. High pressure liquid chromatographic analysis of the aqueous phase demonstrated two GSH adducts of CCl4 metabolites. One adduct was oxygen-dependent and was identified as diglutathione carbonate by its co-elution with a diglutathione carbonate standard. Its formation showed no evidence of saturation when GSH concentrations as high as 10 mM were used, indicating that the overall process was nonenzymatic. Formation of the other adduct was greatest under the lowest oxygen concentration studied and none occurred at oxygen tensions of 5% or greater. Based on experiments with radiolabeled CCl4 and GSH, this metabolite appeared to be a product of one molecule each of CCl4 and GSH. Formation of this adduct had enzymatic characteristics. It was saturable with respect to GSH with an apparent Km of 70 microM, and other thiol compounds that were tested could not substitute for GSH. The adduct was unstable during isolation attempts and was not characterized further. Formation of these two GSH adducts could account for some of the protection by GSH against CCl4 injury.

Animals↗
PubMed1987

Effect of oxygen tension on the generation of alkanes and malondialdehyde by peroxidizing rat liver microsomes.

The alkanes, ethane and pentane, are often used as indices of lipid peroxidation. Because it has been indicated that O2 tension can affect the yield of these compounds, a systematic study of this was carried out. Rat liver microsomes were peroxidized using an iron-ascorbate system. The incubations were carried out in sealed flasks at 37 degrees under N2 and various concentrations of O2 up to 100%. Ethane and pentane production were measured by gas chromatography, and malondialdehyde was measured by the thiobarbituric acid reaction. Microsomal fatty acids were measured by gas chromatography. Polyunsaturated fatty acids were lost during lipid peroxidation. There was no loss of saturated or monounsaturated fatty acids. Loss of polyunsaturated fatty acids correlated with O2 tension in the flask. Half-maximal losses of docosahexaenoic acid, arachidonic acid, and linoleic acid occurred at 3, 5, and 35% O2 respectively. Malondialdehyde formation reflected polyunsaturated fatty acid loss at all O2 concentrations. Alkane formation reflected polyunsaturated fatty acid loss below 5% O2 but not above it. The ratio of alkane formed to precursor polyunsaturated fatty acid lost decreased progressively as O2 concentration was increased above 5%. For example, the molar yield of pentane formed per precursor polyunsaturated fatty acid lost was 0.3% at 5% O2 but only 0.003% at 100% O2. This indicates that quantitation of lipid peroxidation using alkane formation requires consideration of O2 tension at the site of alkane formation.

Animals↗
PubMed1986

Hyperbaric oxygen protection against carbon tetrachloride hepatotoxicity in the rat. Association with altered metabolism.

Because reports have appeared suggesting that hyperbaric O2 treatment protects against the hepatotoxicity of CCl4 in humans, studies were undertaken in rats to assess this possibility and to explore its mechanism. Treatment with 2 atm of O2 for 6 h after intragastric administration of CCl4 (2.6 mmol/100 g) improved survival from 31% to 96%. The same treatment administered 24 h after the CCl4 improved survival from 36% to 50%. The protective effect does not appear to be mediated through changes in excretion or distribution because exhalation of CCl4 was not increased, and hepatic CCl4 concentration was not decreased by hyperbaric O2. Changes in CCl4 metabolism were observed, which could explain the protection. Hyperbaric O2 treatment inhibited in vivo conversion of CCl4 to its volatile metabolites CHCl3 and CO2 by 52% in the 10 h following CCl4 dosing. The predominant effect was on CO2, which is quantitatively the more significant metabolite. Studies with hepatic microsomes isolated from these rats demonstrated that hyperbaric O2 treatment diminished their capacity to metabolize CCl4 to CO2, and O2-dependent process. It had no effect on the metabolism of CCl4 to CHCl3, an O2-inhibited process. These results indicate that hyperbaric O2 suppresses the microsomal mechanism for metabolizing CCl4 in the presence of O2. Because the mechanism of CCl4 hepatotoxicity is thought to be the same in the rat and in humans, hyperbaric O2 therapy is recommended for treatment of CCl4 poisoning in humans.

Animals↗
PubMed1985

Selenium and drug metabolism--III. Relation of glutathione-peroxidase and other hepatic enzyme modulations to dietary supplements.

Male mice were fed a torula yeast-based diet containing different amounts of added selenium for a period of 4 months. Liver glutathione peroxidase activity assayed with H2O2 showed a logarithmic dependence on dietary selenium with a saturation plateau above 2 ppm Se and an extrapolated zero of 0.02 ppm Se. In contrast, liver selenium content and GSH-Peroxidase activity showed a linear correlation. Glutathione peroxidase activity became undetectable at a liver Se content of about 90 ng Se/g liver wet wt. Thus, about 10% of liver selenium is not related to GSH-Px activity. Five dietary groups were supplemented, respectively, with 0, 0.05, 0.5, 5.0 and 10 ppm Se in the form of Na2SeO3. Some changes in drug metabolism enzymes were observed with the high Se diets. An increase occurred in Non-Se-GSH activity as well as in ethacrynic acid-assayed GSH transferase, these are interpreted as early signs of Se toxicity. The diet containing 0.01 ppm Se with no supplementary Se produced the multiple hepatic enzyme modulations which were previously reported. The animals raised on this very low Se diet had normal hepatic contents of glutathione, alpha-tocopherol, calcium, magnesium, iron, zinc, copper and manganese compared to controls supplemented with 0.5 ppm Se. However, significant changes in the microsomal fatty acid pattern were observed while the total phospholipid content as well as membrane fluidity showed no differences between the two dietary groups.

Animals↗
PubMed1984

Selenium and drug metabolism--II. Independence of glutathione peroxidase and reversibility of hepatic enzyme modulations in deficient mice.

Male mice were fed a diet containing less than 0.01 ppm selenium (Se-) for 6 months. A control group received the same diet containing 0.5 ppm selenium (Se+). In the livers of the Se- animals a drastic decrease in glutathione peroxidase (GSH-Px) activity was observed. It reached undetectable levels after 17 days of the Se- diet. At that time, GSH-transferase activity began to increase significantly, followed by changes in many other enzyme activities. After the 60th day, these enzyme modulations had reached a plateau with the following percentage changes compared to controls: GSH-transferases: 320% (1,2-dichloro-4-nitrobenzene), 218% (1-chloro-2,4-dinitrobenzene); glutathione reductase: 160%; ethoxycoumarin deethylase: 330%; cytochrome P-450-hydroperoxidase: 230%; heme oxygenase: 240%; UDP-glucuronyltransferase: 200%; GSH-thioltransferase: 64%; sulphotransferase: 62%; NADPH-cytochrome-P-450-reductase: 65%; flavin-containing mono-oxygenase: 57%. No significant changes were observed for GSH-transferase activity assayed with ethacrynic acid or for microsomal H2O2 formation and aniline hydroxylase activity. In single-pulse repletion experiments by injection of 250 micrograms selenium/kg body wt, different individual time constants for the recovery process of the enzymatic perturbations were observed. The half-times for the recovery ranged from 5.7 hr for the microsomal NADPH-cytochrome-P-450 reductase to over 29 hr for GSH-Px up to 44 hr for part of the GSH-transferase activity. 250 micrograms selenium/kg body wt were needed to restore 50% of GSH-Px activity in the long-term Se- mice compared to Se+ controls. All other enzymatic changes in the Se- mice needed a dose of 7 micrograms selenium/kg body wt for 50% restorage . The results demonstrate that processes other than those related to GSH-Px take place in a later phase of selenium deficiency in mouse liver with a chronologically common beginning. The different repletion and depletion kinetics as well as the different need of these processes for the trace element are discussed with respect to the existence of two separate selenium pools.

Animals↗
PubMed1983

Selenium and drug metabolism--I. Multiple modulations of mouse liver enzymes.

Male albino mice were raised on diets containing less than 10 ppb selenium (Se-) or supplemented with 0.5 ppm selenium (Se+) for 6 months. In the (Se-) group total liver selenium was less than 10% of the control, liver selenium-dependent glutathione peroxidase (GSH-Px) less than 2%. The specific activities of catalase and superoxide dismutase showed essentially no differences between the dietary groups. Several phase I-related specific enzyme activities were measured in liver microsomes. No significant differences between the two animal groups were found for cytochrome P-450 and b 5 content, NADH-cytochrome b 5 reductase, as well as for aniline hydroxylation and aminopyrine dealkylation rates. In (Se-) microsomes, NADPH-cytochrome P-450 reductase activity was about half that found in (Se+) microsomes. An increase in microsomes from (Se-) mice was found for 7-ethoxycoumarine deethylation rate (460%), cytochrome P-450 hydroperoxidase activity (170%), and heme oxygenase (276%). The N-oxidation rate of the flavin-containing monooxygenase decreased by 35%, the N-demethylation rate by 50% in (Se-) animals. Stopped-flow measurements of the reduction rates of microsomal pigments did not support evidence for limitations in microsomal electron supply during selenium deficiency. Among the phase II reactions examined, sulfotransferase activity towards 4-nitrophenol was 47% of the controls in Se-deficient liver cytosols while UDP-glucuronyl transferase activity towards this substrate increased to 215%. Glutathione-S-transferase activity was much higher in (Se-) livers than in (Se+): 310% with 1,2-dichloro-4-nitrobenzene, 255% with 1-chloro-2,4-dinitrobenzene and 120% with ethacrynic acid as substrate. The data indicate that in addition to GSH-Px many other enzyme activities in mouse liver are affected by prolonged dietary selenium deficiency. These effects might be useful in assessing the severity of selenium deficiency. A microsomal selenium-dependent metabolic modulator is discussed as a possible mechanism.

Cytochrome P-450 Enzyme System↗
PubMed1982

Chemically-induced glutathione depletion and lipid peroxidation.

Malondialdehyde (MDA) formation in mouse liver homogenates was measured in the presence of various glutathione depletors (5 mmol/l). After a lag phase of 90 min, the MDA formation increased from 1.25 nmol/mg protein to 14.5 nmol/mg in the presence of diethyl maleate (DEM), to 10.5 with diethyl fumarate (DEF) and to 4 with cyclohexenon by 150 min. It remained at 1.25 nmol/mg with phorone and in the control. On the other hand, glutathione (GSH) dropped from 55 nmol/mg to 50 nmol/mg in the control to, less than 1 with DEM, to 46 with DEF, to 3 with cyclohexenon and to 7 with phorone. The data show that the potency to deplete GSH is not related to MDA production in this system. DEM stimulated in vitro ethane evolution in a concentration-dependent manner and was strongly inhibited by SKF 525A. From type I binding spectra to microsomal pigments the following spectroscopic binding constants were determined: 2.5 mmol/l for phorone, 1.2 mmol/l for cyclohexenon, 0.5 mmol/l for DEM and 0.3 mmol/l for DEF. In isolated mouse liver microsomes NADPH-cytochrome P-450 reductase and NADH-cytochrome b5 reductase activity were unaffected by the presence of DEM, whereas ethoxycoumarin dealkylation was inhibited. Following in vivo pretreatment, hepatic microsomal electron flow as determined in vitro was augmented in the presence of depleting as well as non-depleting agents, accompanied by a shift from O2- to H2O2 production. It is concluded that it is not the absence of GSH which causes lipid peroxidation after chemically-induced GSH depletion but rather the interaction of the chemicals with the microsomal monoxygenase system.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1982

Interim report a study of danazol for the treatment of endometriosis.

Ninety-six infertile women with laparoscopically confirmed endometriosis received danazol (800 mg daily) for 6 months. Despite their prevalence, side effects generally were tolerable and did not contraindicate use of the drug. The mean resolution of peritoneal endometriosis, measured in 44 patients, was 63%. However, individual responses varied considerably. The mean resolution of ovarian endometriosis in 28 patients was 45%. Resolution of less than 1 cm involvement (57%) was similar to that of peritoneal endometriosis, but for more extensive ovarian disease it was only 37% to 40%. Preoperative use of danazol facilitated surgical removal of disease and probably reduced the risk of postoperative adhesions. Pregnancy rates, though reported, are not analyzed because of the brevity of follow-up to date.

Danazol↗
PubMed1980

Organ chemiluminescence: noninvasive assay for oxidative radical reactions.

In situ and perfused rat livers showed a spontaneous chemiluminescence of 7-12 counts/sec . cm2 (corresponding to 7-12 x 10(3) photons/sec . cm2); chemiluminescence was increased up to 30 times by infusion of exogenous hydroperoxides. The chemiluminescence of the perfused liver was oxygen dependent. Ethyl, t-butyl, and cumene hydroperoxides were almost equally effective in inducing light emission in the perfused liver. Glutathione release and chemiluminescence showed a parallel increase upon hydroperoxide supply to the perfused liver. A partial spectral analysis of the chemiluminescence of the perfused liver showed a predominance of red-light-emitting species, presumably arising from the singlet oxygen dimol-emission peaks. Many side reactions derived from the complex free radical sequence of lipid peroxidation could afford the chemistry leading to light emission, which represents only about 10(-14) of the utilization of peroxide.

Animals↗
PubMed1979

Chemiluminescence of Acanthamoeba castellanii.

1. Chemiluminescence of Acanthomoeba castellanii in the presence of O2 was of similar intensity in organisms harvested early or late during exponential growth [when cyanide (1 mM) stimulates or inhibits respiration respectively]. 2. Cyanide (up to 1.5 mM) stimulated photoemission in both types of organism by 250--300 photons/s per 10(7) cells above the value observed under aerobic conditions. 3. 'Dibromothymoquinone' (2,5-dibromo-6-isopropyl-3-methyl-p-benzoquinone) (up to 80 microM) further increased chemiluminescence. 4. Similar responses were also demonstrated in whole homogenates and in subcellular fractions; 36% of the chemiluminescence was provided by a fraction sedimenting at 100000g-min, and 20% in that fraction that was non-sedimentable at 200000g-min. 5. Mitochondrial substrates (succinate, 2-oxoglutarate, NADH) in the presence or absence of ADP and Pi or peroxisomal substrates (glycollate, urate or ethanol) gave no increases in light emission by whole homogenates or in any of the fractions. 6. It is suggested that reactions responsible for production of chemiluminescence are those primarily producing superoxide anions and leading to lipid peroxidation and singlet-oxygen formation. Photoemission enhancement and superoxide dismutase inhibition showed similar cyanide concentration-dependencies.

Amoeba↗
PubMed1979

Increase in levels of cyclic AMP during avian limb chondrogenesis in vitro.

In the present study the level of cAMP was measured during in vitro chondrogenesis of wing mesenchyme of stage 24 chick embryos and was found to increase significantly from 6.3 pmol/mg protein at the end of the first day of culture to 9.7 pmol/mg protein on the second day, when chondrogenic expression is first detected by the appearance of an Alcian blue staining extracellular matrix. Nonchondrogenic cultures derived from wings of stage 19 embryos had a lower level of cAMP (4.4 +/- 0.07 pmol/mg protein). The level of cAMP in intact wings was 4.5 +/- 0.4 pmol/mg protein and did not change between stages 19 through 25. The correlatin between increased levels of cAMP and the onset of chondrogenesis is consistent with a role of cAMP in the expression of differentiated functions in chondrocytes, as well as in some other cell types.

Animals↗
PubMed1976

[Silent hip dysplasias (author's transl)].

Clinical and X-ray examinations for hip dysplasias in 500 babies in one ward showed 40% wrongly positive and 5.6% wrongly negativ (silent or masked) results, control of which necessiates roentgenograms in the second or third month or coltrolled spreading immediately after birth.

Age Factors↗