There is increasing evidence that the deteriorative reaction of lipid peroxidation is involved in oxidant-chemical toxicities, inflammatory disease states, and normal metabolic activities. The research proposed will emphasize use of the method developed in this laboratory for measurement of in vivo lipid peroxidation by analysis of respiratory hydrocarbon gas products of lipid hydroperoxide decomposition. Pentane, deriving from omega 6-unsaturated fatty acid hydroperoxides, and ethane, deriving from omega 3-unsaturated fatty acid hydroperoxides, have been focused on in past research. Future work will include measurement of other hydrocarbon gases and acetone, which can arise form lipid peroxidation as well as impaired carbohydrate metabolism caused by damage to microsomal enzymes by peroxidation in vivo. Experimental systems to test lipid peroxidation induced by strong chemical oxidants over short time periods will be investigated. Hydrocarbon gas and acetone production via lipid peroxidation will be related to known activities of the microsomal monooxygenase system. Stimulators and depressors of this system will be used in vivo to relate the biochemical reactions to lipid peroxidation, as measured by the respiratory gases indicated. The involvement of toxic compounds, such as halogenated hydrocarbons, hydroperoxides, heavy metals, and carcinogens, in induction of lipid peroxidation will be determined. Widely used animal models of inflammatory diseases, such as arthritis, diabetes, and atheroschlerosis will be studied to determine in vivo the involvement of lipid peroxidation in the initiation and the course of these diseases. In all experiments where lipid peroxidation is found to occur, the ameliorative effect of the dietary antioxidants vitamin E and selenium, or injected vitamin E will be ascertained. The biological activities of alpha- and gamma-tocopherol will be compared with their effectiveness in inhibition of pentane production.