Exhaled ethane and pentane have been used as indices of lipid peroxidation to examine the importance of this process in pathological conditions. Recent studies have demonstrated that these compounds are metabolized by the rat and that the liver plays a major role in this. Thus, exhaled hydrocarbon depends on metabolism of these compounds as well as on the formation rate which is the parameter related to lipid peroxidation. This proposal will develop and validate a pharmacokinetic model which can measure metabolism of hydrocarbons and correct exhaled hydrocarbon values to yield formation rates, thus improving measurement of lipid peroxidation. This will be carried out by measuring disappearance of the hydrocarbons from the atmosphere of a closed chamber containing the rat and, at the same time, measuring blood levels of the hydrocarbons. A second major approach to the problem will be to develop inhibitors of metabolism of the hydrocarbons which do not influence their formation. When such inhibitors are given, exhaled hydrocarbon should represent the formation rate. The metabolism of the hydrocarbons by isolated cel fractions and isolated liver cells will be used to determine the mechanism of inhibitors such as 4-methylpyrazole. The effect of the inhibitors will be studied in rats in the chamber to determine: (1) their effectiveness as inhibitors of hydrocarbon metabolism and (2) their effect on hydrocarbon formation. An ideal inhibitor would inhibit metabolism without affecting formation.
| Burk, R F; Ludden, T M (1989) Exhaled alkanes as indices of in vivo lipid peroxidation. Biochem Pharmacol 38:1029-32 |
| Daugherty, M S; Ludden, T M; Burk, R F (1988) Metabolism of ethane and pentane to carbon dioxide by the rat. Drug Metab Dispos 16:666-71 |
| Allerheiligen, S R; Ludden, T M; Burk, R F (1987) The pharmacokinetics of pentane, a by-product of lipid peroxidation. Drug Metab Dispos 15:794-800 |
| Reiter, R; Burk, R F (1987) Effect of oxygen tension on the generation of alkanes and malondialdehyde by peroxidizing rat liver microsomes. Biochem Pharmacol 36:925-9 |
