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Biomedical subjects

A Sevanian

Publications and source records attributed to A Sevanian.

At least 127 records · Page 7Linked to original sources
PubMed1985

Superoxide dismutase in ocular structures.

Specific immunohistochemical localization of superoxide dismutase in ocular tissue of Lewis rats revealed the presence of this enzyme predominantly in the corneal epithelium, endothelium, apical regions of the posterior epithelium of the iris, nonpigmented inner ciliary epithelium, lens epithelium, inner segments of photoreceptor cell layer of the retina, and retinal pigment epithelium. This enzyme is distributed primarily in those ocular structures which may be frequently exposed to superoxide or its metabolites under physiologic conditions and in such pathologic processes as intraocular inflammations. It thus appears that superoxide dismutase and other antioxidants may play a protective role in preventing the damaging effects of oxygen radicals.

Animals↗
PubMed1984

Measurement of uric acid, ascorbic acid, and related metabolites in biological fluids.

A rapid and quantitative method for the simultaneous measurement of uric acid, ascorbic acid, and related metabolites in biological fluids is described. This method makes use of anion-exchange extraction columns to isolate the desired compounds from a wide range of biological fluids, and anion-exchange HPLC with ultraviolet detection for their separation and measurement. By this procedure the contents of uric and ascorbic acids in human serum and urine were estimated. Furthermore, the oxidation of uric acid to allantoin and ascorbic acid to dehydroascorbic acid could be readily monitored.

Allantoin↗
PubMed1984

Cholesterol epoxide is a direct-acting mutagen.

A 24-hr treatment of V79 Chinese hamster lung fibroblasts with 12.4 microM cholesterol 5 alpha, 6 alpha-epoxide induced 8-azaguanine-resistant mutants at frequencies 4.6- to 11.8-fold higher than the spontaneous mutation rate. We show that cholesterol epoxide, which is produced by in vivo cholesterol oxidation, is a weak direct-acting mutagen. Cholesterol epoxide was found to be accumulated by cells and transformed to cholestane-3 beta, 5 alpha, 6 beta-triol, which was more toxic and a more potent inhibitor of DNA synthesis than the epoxide but, at concentrations less than 17.8 microM, was not significantly mutagenic. Consideration of the rates of cholesterol epoxide conversion to cholestane triol shows that this conversion can result in abolition of the mutagenicity of the epoxide. Conditions under which conversion of the epoxide to the triol is low, as in the case of low epoxide hydrolase activity, favor mutagenicity whereas rapid conversion to triol favors cytotoxicity.

Animals↗
PubMed1983

The influence of phospholipase A2 and glutathione peroxidase on the elimination of membrane lipid peroxides.

The relationship between release of membrane lipid peroxidation products and phospholipase action was examined. Rat liver microsomes and phosphatidylcholine liposome-phospholipase A2 preparations were subjected to iron ascorbate-induced lipid peroxidation. Peroxidation products were characterized by measurement of malondialdehyde and lipid peroxides. Experiments were designed to demonstrate phospholipase dependent removal of peroxidation products origination in the membrane. Increased lysophosphatidylcholine formation was evident following lipid peroxidation in phospholipase A2-containing liposomes which was inhibited by p-bromophenacyl bromide and mepacrine. Lipoxygenase-dependent oxygen consumption, as well as peroxide transfer from microsomes to the incubation medium, was largely dependent on phospholipase and could be diminished by phospholipase inhibitors. Furthermore, lipid hydroperoxides formed by subjecting phosphatidylcholine liposomes to iron ascorbate-induced peroxidation, or those present in aged liposomes, were effectively reduced by glutathione peroxidase when phospholipase A2 was present in the assay. Low level glutathione peroxidase activity was observed in the absence of phospholipase A2.

Animals↗
PubMed1982

Influence of vitamin E and nitrogen dioxide on lipid peroxidation in rat lung and liver microsomes.

Rat lung and liver microsomes were used to examine the effects of dietary vitamin E deficiency on membrane lipid peroxidation. Microsomes from vitamin-E-deficient rats displayed increased lipid peroxidation in comparison to microsomes from vitamin-E-supplemented controls. The extent of lipid peroxidation, as determined by measurement of thiobarbituric acid reacting materials, was enhanced by addition of reduced iron and ascorbate (or NADPH). Rats fed a vitamin-E-supplemented diet and exposed to 3 ppm NO2 for 7 days did not exhibit increases in microsomal lipid peroxidation compared to air-breathing controls. However, increase were found in microsomes prepared from rats fed a vitamin-E-deficient diet and exposed to NO2. Lung microsomes from vitamin-E-fed rats contained almost 10 times as much vitamin E as liver microsomes when expressed in terms of polyunsaturated fatty acid content. The extent of lipid peroxidation was, in turn, considerably less in lung than in liver microsomes. Lipid peroxidation in lung microsomes from vitamin-E-deficient rats comparable to liver microsomes from vitamin-E-supplemented rats as was the content of vitamin E in these respective microsomal samples. A combination of vitamin E deficiency and NO2 exposure resulted in the greatest increases in lung and liver microsomal lipid peroxidation with the largest relative increases occurring in lung microsomes. An inverse relationship was found between the extent of lipid peroxidation and vitamin E content. Most of the peroxidation in lung microsomes appeared to proceed nonenzymatically whereas peroxidation in liver was largely enzymatic. Vitamin E appears to be assimilated by the lung during oxidant inhalation, but with dietary vitamin E deprivation, the margin for protection in lung may be less than in liver.

Animals↗
PubMed1981

Phospholipid synthesis in fetal lung organotypic cultures and isolated type II pneumocytes.

Type II pneumocytes from fetal rabbit lungs were grown in an organotypic system and used to study surfactant phospholipid synthesis. This organotypic system was further employed as a means for isolating purified type II cells which were grown in monolayer cultures. Phospholipid synthetic properties for these purified type II cells at different stages of culture were studied using the radioactivity labeled substances: palmitate, choline and acetate. Additionally, fibroblasts were recovered from the organotypic system and grown in isolated cultures or in combination with type II cells. A comparison of the phospholipid composition and biosynthesis for these cell preparations indicated that in all instances, with the exception of fetal lung fibroblasts, the cultures were capable of producing saturated phosphatidylcholine as a major phospholipid product. The relative molar incorporation into phospholipids for the substrates studied differed depending on the type cell preparation being examined. The formation of surfactant phospholipids appeared most similar for the organotypic system and mixed fibroblast/type II cell preparations. Furthermore, a mixed culture of fibroblasts and type II cells produced larger proportions of surfactant phospholipids than type II cells alone. These observations indicate that the organotypic system is a useful model for examining fetal lung surfactant phospholipid synthesis and may also be employed as a simple means or isolating fetal type II pneumocytes.

Acetates↗
PubMed1981

Metabolism of epoxidized phosphatidylcholine by phospholipase A2 and epoxide hydrolase.

The isolation and measurement of phospholipid epoxides as major peroxidation products in biomembrane preparations prompted an investigation of enzymatic mechanisms which may be responsible for their elimination. Analysis of microsomal epoxide hydrolase and phospholipase A2 activity against a phospholipid epoxide commonly encountered in tissues indicated it to be a poor substrate for epoxide hydrolase, but rapidly hydrolyzed by phospholipase A2. Microsomal and purified phospholipase A2 preparations hydrolyzed the phospholipid epoxide at rates 2-fold greater than were observed with a monoenoic phospholipid from which the epoxide would be derived. The product fatty acid epoxide, cis-9,10-epoxystearic acid, was rapidly hydrated by microsomal and cytosolic epoxide hydrolase. On the basis of earlier reports demonstrating increased phospholipase activity against oxidized phospholipids, and on the results of the present study, a model for the metabolism of oxidized membrane phospholipids is proposed.

Animals↗
PubMed1981

The effect of oxygen exposure on erythrocyte phospholipid composition.

Phospholipids in plasma and erythrocytes of rats exposed to 100% oxygen for 3 days were analyzed. Exposed rats contained lower quantities of several phospholipids in both plasma and erythrocytes than in matched controls. Pronounced decreases were found in phosphatidylcholine and lysophosphatidyl choline. The proportion of disaturated species in erythrocyte phosphatidylcholine was significantly greater after oxygen exposure. There was an increase in percentage of saturated fatty acids with a proportionate decrease in percentage of unsaturated fatty acids. The increase in saturation was associated primarily with palmitate while decreased unsaturation involved primarily linoleic acid. In plasma the proportions of stearic acid increased while those of linoleic, arachidonic and docosahexaenoic acids decreased in phosphatidylcholine. Damage to cell lipids may account for increased hemolysis which occurs after exposure to high oxygen concentrations. Erythrocytes recovered following oxygen exposure contained phospholipid species commonly found in immature red blood cells.

Animals↗
PubMed1980

Lipid epoxide hydrolase in rat lung preparations.

The activity of rat lung epoxide hydrolase (epoxide hydrolase, EC 3.3.2.3) was studied using two lipid epoxides which can be isolated from lung tissue. These epoxides displayed different Km,app and hydration rates. Methyl cis-9,10-epoxystearate was hydrated 20-times more rapidly than cholest-5 alpha,6 alpha-epoxy-3 beta-ol. The Km for the lung microsomal enzyme was variable and dependent on the microsome concentration in the medium. A soluble epoxide hydrolase was also detected in both lung and liver. This enzyme appears similar to the microsomal enzyme in its activity toward methyl epoxystearate. The measured activities for liver microsomal epoxide hydrolase were over 8-times those for lung microsomes; activity against cholesterol epoxide was 40-times greater for liver. In spite of the slow rates measured with cholesterol epoxide in lung preparations, this compound was an effective competitive inhibitor against methyl epoxystearate over a wide concentration range. This suggests that cholesterol epoxide readily binds to epoxide hydrolase and is an effective competitive inhibitor against a much more actively metabolized substrate, methyl epoxystearate. Such circumstances indicate that cholesterol epoxide binds with a high degree of nonproductivity to lung microsomal epoxide hydrolase. This attribute of lung epoxide hydrolase may relate to the relatively high concentrations of cholesterol epoxide found in lung tissue.

Animals↗
PubMed1979

Epoxides as products of lipid autoxidation in rat lungs.

The nature and content of lipid epoxides in rat lung were examined in air-breathing control rats and those exposed to nitrogen dioxide. Exposure to 6.5 ppm NO2 for 24 hr resulted in significantly greater epoxide content in a number of lipid classes. It is proposed that lipid autoxidation in lung tissues may contribute to the levels of epoxide-containing lipids. Furthermore, the processes involved in epoxide formation may be predicted from autoxidation studies utilizing a system of unsaturated fatty acid monolayers on silica gel which serves as a model for biomembranes. The findings indicate that exposure to oxidizing gases can lead to an accumulation of lipid epoxides in both lung parenchymal tissue and on the alveolar surface.

Animals↗
PubMed1979

Inhibition of surfactant production by insulin in fetal rabbit lung slices.

Incorporation of labeled glucose and fatty acid residues into saturated phosphatidylcholine was significantly reduced in lung slices from 27.5 days of gestation fetal rabbits during 90 min incubation in the presence of 100 microU/ml insulin. When 14C-glucose was used as substrate, incorporation into both phosphatidylcholine and saturated phosphatidylcholine was reduced by insulin. This occurred despite an increase in overall glucose utilization by the lung from 11.3 +/- 3.9 to 16.3 +/- 5.2 nmole/g tissue in the presence of insulin (P less than 0.05). A decrease in incorporation of fatty acid residues into saturated phosphatidylcholine was also observed when 14C-palmitate was used as substrate, from 102 +/- 4 to 90 +/- 5 nmole palmitate/g tissue (P less than 0.01). In the presence of insulin, there were significant reductions of both substrates appearing in lysophosphatidylcholine, a precursor of saturated phosphatidylcholine. There was no significant change in incorporation of glucose residues into glycogen or lactate under these conditions.

Animals↗
PubMed1979

Enhancement of fetal lung surfactant production by aminophylline.

Antepartum administration of aminophylline to pregnant rabbits resulted in accelerated formation of phospholipids regarded to be important components of pulmonary surfactant. Increases in the tissue content and synthesis of saturated phosphatidylcholine and phosphatidylinositol were found in lung slice preparations obtained from fetuses previously treated with aminophylline. Synthesis of phospholipids was measured using labeled palmitate, oleate, and glucose as precursors. The results showed increased de novo production of these lipids, and that glucose and glycogen may serve as important precursors. There was a significant reduction in triglyceride content while free fatty acids increased suggesting increased lipolysis in the aminophylline-treated groups, but this did not measurably affect the rate of labeled palmitate incorporation into total phospholipids.

Aminophylline↗
PubMed1978

Effects of cortisol and aminophylline upon survival, pulmonary mechanics, and secreted phosphatidyl choline of prematurely delivered rabbits.

Rabbits delivered at 27.0 days of gestation were studied after administration of cortisol (2 mg/kg/day), aminophylline (6.25 mg/kg/day), or sterile saline to the does on days 24-26 of gestation. Survival at 60 min was 52.9% in the aminophylline-treated group and 22.2% in the control and cortisol-treated groups with all animals being in a warm, oxygen-enriched environment and receiving frequent tactile stimulation. Lung volume at 30 cm H2O was lower in the cortisol-treated group than in the controls or aminophylline-treated group in animals surviving for 60 min (Table 2). The aminophylline-treated group retained significantly more gas at low pressures on the deflation curve (Table 2) and had significantly more phosphatidylcholine recovered in lung lavage fluid (Table 3) than the other groups. Aminophylline appears to have enhanced lung maturation better than cortisol in this experimental model.

Adenosine Monophosphate↗
PubMed1977

Regulation of fetal lung phosphatidyl choline synthesis by cortisol: role of glycogen and glucose.

Twenty pregnant rabbits were studied in pairs. Half were given cortisol subcutaneously on days 24, 25, and 26 of gestation in dosage of 2 mg/kg/day. Half served as controls and received saline. The fetal lungs were studied on the 27th day of gestation by incubating lung slices in the presence of [6-14C]glucose. Glucose consumption significantly increased in the tissue from animals treated with cortisol, 17.61 "/- 5.56 (SD) mumol/g in the controls (P less than 0.05). The glycogen content of tissue treated with cortisol was significantly reduced compared to the controls, 2.42 +/- 0.97 (SD) mg/g wet lung versus 3.81 +/- 1.05 (SD) mg/g (P less than 0.05). Treatment with cortisol resulted in significantly enhanced incorporation of the 14C label into glycogen and phosphatidyl choline (Tables 3 and 4). These data suggest that glucocorticoids affect fetal lung phosphatidyl choline production by promoting glycogenolysis and increasing glucose incorporation into phosphatidyl choline.

Animals↗
PubMed1976

Role of adenosine 3', 5'-monophosphate in maturation of fetal lungs.

Fetal lung cyclic AMP phosphodiesterase, cyclic AMP, phosphatidyl choline, and incorporation of precursors into phosphatidyl choline were measured in rabbits after maternal administration of hydrocortisone phosphate and aminophylline. Both agents inhibited lung phosphodiesterase activity and augmented cyclic AMP concentrations (Table 1). Aminophylline administration was associated with a significant increase in lung saturated phosphatidyl choline (Table 2). Incorporation of [14C] choline and [3H] methionine was increased by both aminophylline and hydrocortisone (Table 3).

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMedDate not supplied

Role of free radicals in uveitis.

In acute inflammation, the tissue damage is generally mediated through polymorphonuclear leukocytes and macrophages. Recent studies on the mechanism of this leukocyte-mediated cytolysis have demonstrated that these cells, on stimulation, release a variety of reactive products. These metabolic products consist of superoxide and hydrogen peroxide, which in turn can form highly reactive species such as hydroxyl radicals. It is believed that these oxygen products play an important role in the tissue damage that occurs in inflammations such as uveitis. The ocular structures contain various antioxidant enzymes that normally protect against free radical mediated injury. In experimental animal models of uveitis, it has been shown that antioxidants and free radical scavengers can function as antiinflammatory agents and can protect the eye from inflammation-mediated tissue damage.

Animals↗