Striatal metabolism of hexanal, a lipid peroxidation product, in the rat

Free radical induced lipid peroxidation may play a role in neurodegeneration and peroxidation leads to the formation of hexanal from omega-6 fatty acids. We have previously demonstrated in vitro that pyruvate dehydrogenase (PDH) catalyzes the condensation of saturated aldehydes with pyruvate to form acyloins. We have further shown in perfused rat heart that hexanal, presumably via PDH, is converted to 3-hydroxyoctan-2-one and that it in turn can be reduced to 2,3-octanediol. We now extend this work using intra-striatal microdialysis to show that this reaction also occurs in rat brain. The reduction of hexanal to hexanol was also evaluated. Microdialysis probes were implanted bilaterally in the striatum and were infused with hexanal with and in the absence of added pyruvate. Analysis of microdialysis samples showed a release of 3-hydroxyoctan-2-one (9.5-10.5 pmol/min), 2,3-octanediol (2.2-2.7 pmol/min) and hexanol (64-74 pmol/min). Pyruvate addition did not increase 3-hydroxyoctan-2-one or 2,3-octanediol production. In a second series of experiments where no exogenous hexanal was infused, endogenous production of 3-hydroxyoctan-2-one (1.0-1.3 pmol/min) and 2,3-octanediol (1.0-1.2 pmol/min) was still observed, although no hexanol was detected. We also investigated the possibility that oxidative stress induced by 1-methyl-4-phenylpyridinium (MPP+) would increase lipid peroxidation resulting in increased production of 3-hydroxyoctan-2-one. Analysis of samples collected following MPP+ infusion indicated no additional increase suggesting that brief exposure to MPP+ does not increase hexanal formation over baseline levels during the experimental period.