Biochemical aspects of chronic hyperoxia in mammals
The primary objective of the work described in this thesis was to investigate some of the effects of chronic oxygen toxicity in mammals. This thesis describes in vivo changes in certain metabolites and enzymes following the exposure of mice and rats to increased concentrations of oxygen at atmospheric pressure. The introductory section reviews the historical background to oxygen toxicity, delineates its two forms and describes their aetiology. The physical and chemical properties of oxygen which contribute to its unusual reactivity are discussed, together with the reactive species of oxygen which may be responsible for its toxicity. To complete the introduction, the known effects of oxygen on metabolism are reviewed. In order to pursue these studies it was necessary to design an apparatus capable of providing a controlled high oxygen atmosphere. Its construction and operation is described. Results obtained indicated that the levels of the protective enzymes superoxide dismutase and catalase varied in lung, liver and brain of mice following exposure to increased oxygen levels. Overall protein levels were also found to vary, so an experiment involving a polyacrylamide gel separation was performed to reveal any qualitative differences. Another experiment monitored the changes in free amino acids in brain, liver, lung and muscle. A few possible deviations from normal were detected but these changes were not consistent between the tissues studied. Results are presented of the changes in some gross physical parameters and the effect of 3 prostaglandin inhibitors on these in vivo changes. Other experiments revealed the changes in haematocrit, in retinol and in haemoglobin levels. For comparative purposes some of the above measurements were also applied to samples of body fluids from men suffering a mild experimental oxygen toxicity. The relevance of these results to the toxic effects of oxygen in mammals is discussed.