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S M Deneke

Publications and source records attributed to S M Deneke.

29 records · Page 2Linked to original sources
PubMed1985

Effects of low protein diets or feed restriction on rat lung glutathione and oxygen toxicity.

Male rats weighing 200-250 g were fed a 25% casein diet in restricted amounts or ad libitum or one of two low protein diets (3 and 0% casein) ad libitum. Decreased tolerance to hyperoxic stress was observed only in the rats fed low protein diets. These animals had a median death time of 49-50 h compared to 58-69 h for feed-restricted or normal control groups. Death was due to accelerated development of lung edema. Changes in total lung levels of glutathione reductase, glucose-6-phosphate dehydrogenase or catalase did not correlate with oxygen sensitivity. Lung glutathione levels were related to the amount of sulfur-containing amino acids in the diet and were depressed in the feed-restricted as well as the protein-restricted groups. However, feed restriction alone did not enhance oxygen toxicity. We conclude that a decrease in lung glutathione may be partially responsible for the increased oxygen sensitivity in the protein-deficient rats, but that other factors are necessary for explanation of the relative oxygen tolerance of the feed-restricted animals with reduced levels of glutathione in the lung.

Amino Acids↗
PubMed1985

Transient depletion of lung glutathione by diethylmaleate enhances oxygen toxicity.

Diethylmaleate (DEM) decreases glutathione (GSH) levels in various organs by enzymatic conjugation with reduced GSH catalyzed by GSH transferase. We have examined levels of GSH, glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PD) in lungs of 200-250-g rats after intraperitoneal injection of 0.5 or 1 g DEM/kg body wt. The GSH levels are severely depressed at 2 and 4 h but have essentially recovered by 12 and 24 h after either dose of DEM. The GR and G6PD activities in the 1 g/kg group are depressed at 4 h to a lesser extent than the GSH levels and also return to normal by 12 and 24 h. These enzymes are not affected in the 0.5 g/kg group. To determine whether these transient decreases in GSH and related enzymes affected O2 tolerance, we exposed rats injected with DEM to greater than 98% O2 and found that halftime (t1/2) for survival was decreased in rats receiving both 0.5 and 1 g DEM/kg body wt when compared with untreated or saline-injected controls (t1/2 control, 74 h; 0.5 g DEM, 59 h; 1 g DEM, 53 h). No deaths occurred in air controls at 1 mg/kg DEM for up to 5 days. DEM, in itself, caused no morphological alteration of the lung. Thus a decrease in lung GSH and related enzymes, occurring by 4 h and reversed by 12 h, has a significant effect on the subsequent progression of lung pathology and indicates that early biochemical events occurring in lungs exposed to hyperoxia may be very important in determining the degree of longer-term damage to rat lungs.

Animals↗
PubMed1983

Ultrastructural changes in bovine pulmonary artery endothelial cells exposed to 80% O2 in vitro.

Bovine pulmonary artery endothelial cells in culture were exposed for up to 7 d to a gas mixture containing 80% O2, 5% CO2, and 15% N2 (hyperoxia) and were compared by phase contrast and electron microscopy to cells exposed to a gas mixture containing 20% O2, 5% CO2, and 75% N2. Cells exposed to hyperoxia became enlarged and showed vacuolization and increased lysosomes within 24 to 48 h. These changes were progressive over the 7 d period of exposure. Between 3 and 7 d of exposure to hyperoxia the cells showed reductions in polysomes and endoplasmic reticulum. Despite the other marked cytoplasmic changes, the appearance of mitochondria of oxygen-exposed cells remained unchanged from those of air-exposed cells throughout the 7 d period. Preconfluent and confluent cells responded qualitatively similarly to hyperoxia, but morphological evidence of injury occurred more rapidly for preconfluent cells. We conclude that the initial early structural injury of the endothelial cell exposed to hyperoxia occurs in lysosomes and that the mitochondrial structure is relatively resistant to injury.

Animals↗
PubMed1983

Potentiation of oxygen toxicity in rats by dietary protein or amino acid deficiency.

Rats fed 3% casein diets for 6 days showed an increased susceptibility to greater than 98% oxygen [mean survival time 46.9 +/- 4.1 (SD) h] compared with animals fed 25% casein diets (mean survival time 60 +/- 5 h). The 3% casein diet did not reduce the responses to hyperoxia of lung glucose-6-phosphate dehydrogenase, glutathione peroxidase, and glutathione reductase (NAD(P)H), which maintain tissue levels of reduced glutathione or lung superoxide dismutase levels. While supplementation of the 3% casein diet with the sulfur-containing amino acids (cysteine, cystine, or methionine) prevented the increased oxygen toxicity, supplementation with leucine, a nonsulfur-containing amino acid, had no effect on potentiation of toxicity. Animals fed the unsupplemented 3% casein diet failed to show an elevation of lung glutathione in response to hyperoxia. When the 3% casein diet was supplemented with cysteine, total lung glutathione levels increased normally during oxygen exposure. Supplementation of the 25% protein diet with cysteine did not further protect these animals. We conclude that potentiation of oxygen toxicity by dietary protein deficiency in the rat is due to the low sulfur-containing amino acid content of the diet; the mechanism of increased toxicity by hyperoxia is probably related to an inability to increase glutathione levels due to a shortage of the cysteine component of the glutathione tripeptide.

Amino Acids↗
PubMed1982

Interaction of oxygen and oxy-radicals with carotenoids.

Dye-sensitized photo-oxidations of liposomes are inhibited by the presence of carotenoids in the membrane. Some carotenoid bleaching occurs during the reaction. It was shown that carotenoids are capable of inhibiting free-radical-induced lipid peroxidation in liposomes as well as singlet oxygen-induced lipid peroxidation. There is little direct effect of lipid peroxides on carotenoid bleaching during the photo-oxidative reactions. The carotenoid bleaching observed during the dye-photosensitized oxidations of the liposomes appears to be due to interactions between the carotenoid pigments and either radical intermediates from type I reactions or direct chemical reaction with singlet oxygen in a type II reaction. It was concluded that carotenoid pigments function as protective agents by quenching triplet sensitizers, singlet oxygen, and radical intermediates.

Carotenoids↗
PubMed1979

Enhancement by disulfiram (Antabuse) of toxic effects of 95 to 97% O2 on the rat lung.

Disulfiram (Antabuse), a drug used in alcohol aversion therapy, has been demonstrated to protect various species against hyperbaric O2 toxicity. In contrast, we have found that disulfiram accelerates the onset of pulmonary edema and death of rats exposed to normobaric 95 to 97% O2. When rats were given 200 mg of disulfiram per kg b.wt., 100% of the rats died at 24 to 48 hr of O2 exposure whereas only 5% of the rats died when exposed to O2 without disulfiram. This effect was not seen with an equal dose of diethyldithiocarbamate, the reduced monomer of disulfiram. The toxic effect was not due to an inhibition of superoxide dismutase, nor did disulfiram significantly affect the level of glutathione or change the reduced to oxidized glutathione ratio in the lung. Concurrent administration of 200 mg per kg b.wt. of ascorbate, vitamin E or reduced glutathione or 100 mg/kg of catalase did not affect the toxic response.

Animals↗
PubMed1978

Absence of inductive effect of hyperoxia on superoxide dismutase activity in rat alveolar macrophages.

Mammalian cells may be protected from damage by hyperoxia through the induction of enzymes that reduce destructive oxygen-free radicals. One such enzyme is superoxide dismutase, which reduces superoxide to form hydrogen peroxide and O2. We studied the concentration of this enzyme in rat alveolar macrophages exposed to 85 to 90 per cent O2 in vitro for as long as 6 days and in macrophages obtained from rats exposed to 85 to 97 per cent O2 in vivo for as long as 7 days. In no case was there an increase in superoxide dismutase in rat alveolar macrophages, despite a doubling of superoxide dismutase in whole lungs of rats exposed to 85 to 90 per cent O2 for 7 days in vivo. We concluded that the macrophage of the adult rat does not defent itself against hyperoxia by the induction of superoxide dismutase and does not participate in the increased superoxide dismutase activity of lungs of these animals exposed to hyperoxia.

Animals↗