Abstract: 4-Hydroxy-2-nonenal (HNE) is an endogenous product of lipid
peroxidation, which is believed to play a biological role in the pathogenesis
of various diseases. HNE is formed as a racemic mixture of (R)- and (S)-
enantiomers. These enantiomers differ in their biological properties. The aim
of this study was to investigate separately the in vivo metabolism of the two
HNE enantiomers in male rats after intravenous administration of the
corresponding radiolabeled compounds and to compare the results with those
obtained with the racemic mixture. Although the difference in the excretion
rates was not statistically significant, the HPLC profiles of urinary
metabolites showed qualitative and quantitative differences between the two
enantiomers. The level of 3-mercapturic acid-1,4-dihydroxynonane, which is
considered as the major urinary metabolite of HNE, was significantly lower in
the case of (S)-HNE injected rats. In vitro studies using rat liver cytosolic
incubations and HNE-glutathione conjugate as substrate were performed to
clarify the intermediate pathways involved in their metabolism. Large
differences were obtained in the reduction and retro-Michael conversion steps
of the metabolism between the conjugates originating from the two
enantiomers.
