Evidence from in vivo 31-phosphorus magnetic resonance spectroscopy phosphodiesters that exhaled ethane is a biomarker of cerebral n-3 polyunsaturated fatty acid peroxidation in humans

Abstract

Background: This study tested the hypothesis that exhaled ethane is a biomarker of cerebral n-3 polyunsaturated fatty acid peroxidation in humans. Ethane is released specifically following peroxidation of n-3 polyunsaturated fatty acids. We reasoned that the cerebral source of ethane would be the docosahexaenoic acid component of membrane phospholipids. Breakdown of the latter also releases phosphorylated polar head groups, giving rise to glycerophosphorylcholine and glycerophosphorylethanolamine, which can be measured from the 31-phosphorus neurospectroscopy phosphodiester peak. Schizophrenia patients were chosen because of evidence of increased free radical-mediated damage and cerebral lipid peroxidation in this disorder.

Methods: Samples of alveolar air were obtained from eight patients and ethane was analyzed and quantified by gas chromatography and mass spectrometry (m/z = 30). Cerebral 31-phosphorus spectra were obtained from the same patients at a magnetic field strength of 1.5 T using an image-selected in vivo spectroscopy sequence (TR = 10 s; 64 signal averages localized on a 70 x 70 x 70 mm3 voxel). The quantification of the 31-phosphorus signals using prior knowledge was carried out in the temporal domain after truncating the first 1.92 ms of the signal to remove the broad component present in the 31-phosphorus spectra.

Results: The ethane and phosphodiester levels, expressed as a percentage of the total 31-phosphorus signal, were positively and significantly correlated (rs = 0.714, p < 0.05).

Conclusion: Our results support the hypothesis that the measurement of exhaled ethane levels indexes cerebral n-3 lipid peroxidation. From a practical viewpoint, if human cerebral n-3 polyunsaturated fatty acid catabolism can be measured by ethane in expired breath, this would be more convenient than determining the area of the 31-phosphorus neurospectroscopy phosphodiester peak.

Figure 1

Levels of ethane (in ppb) in the expired breath of patients with schizophrenia plotted against their cerebral percentage PDE values, together with the straight line of best fit. The 95 per cent confidence interval for this regression line is also shown.