Time-course of oxidation of lipids in human cerebrospinal fluid in vitro

Oxidative mechanisms play an important role in the pathogenesis of Alzheime r's disease, Parkinson's disease and other neurodegenerative diseases. To a ssess whether the oxidation of brain lipoproteins plays a role in the devel opment of these pathologies; we investigated whether the lipoproteins of hu man cerebrospinal fluid (CSF) are susceptible to oxidative modification in vitro. We studied oxidation time-course for up to 100 h of human CSF in the absence (autooxidation) or presence of exogenous oxidants. Autooxidation o f diluted CSF was found to result in a slow accumulation of lipid peroxidat ion products. The time-course of lipid hydroperoxide accumulation revealed three consecutive phases, lag-phase, propagation phase and plateau phase. Q ualitatively similar time-course has been typically found in human plasma a nd plasma lipoproteins. Autooxidation of CSF was accelerated by adding exog enous oxidants, delayed by adding antioxidants and completely inhibited by adding a chelator of transition metal ions. Autooxidation of CSF also resul ted in the consumption of endogenous ascorbate, ol-tocopherol, urate and li noleic and arachidonic acids. Taking into account that (i) lipid peroxidati on products measured in our study are known to be derived from fatty acids, and (ii) lipophilic antioxidants and fatty acids present in CSF are likely to be located in CSF lipoproteins, we conclude that lipoproteins of human CSF are modified in vitro during its autooxidation. This autooxidation appe ars to be catalyzed by transition metal ions, such as Cu(II) and Fe(III), w hich are present in native CSF. These data suggest that the oxidation of CS F lipoproteins might occur in vivo and play a role in the pathogenesis of n eurodegenerative diseases.