Objective: To test the hypothesis that enhanced oxidative stress during pregnancies complicated by preeclampsia is associated with improper copper (Cu) binding by plasma albumin, resulting in enhanced Cu redox-cycling activity and that altered Cu binding, in turn, is caused by interactions of excessive amounts of free fatty acids with albumin.
Study design: We studied binding and redox-cycling activity of Cu in 17 normal pregnancy and 17 preeclampsia plasma samples. Binding of exogenous Cu in plasma samples was quantified indirectly using spectrophotometric measurements of its complex with a specific chelator of Cu(I), bathocuproine disulfonate. Redox-cycling activity of Cu in plasma samples was estimated by electron paramagnetic resonance (EPR) spectroscopy of ascorbate radicals formed during one-electron oxidation of ascorbate by redox-active catalytic Cu. Formation of Cu/albumin complexes in model systems in the presence and absence of fatty acids was studied using EPR spectroscopy of Cu(II)/albumin.
Results: We found that preeclampsia plasma (as compared to normal pregnancy plasma) (1) displays elevated endogenous ascorbate redox-cycling that is normalized by a Cu(II) chelator, cuprizone I, (2) has lowered capacity to bind and redox-regulate exogenously added Cu, and (3) responds to treatment with fatty-acid-free albumin by diminished ascorbate oxidizing activity. Conversely, addition of free fatty acid (oleic acid) to normal pregnancy plasma sample yields increased ascorbate redox-cycling activity. Our model experiments showed that Cu-dependent redox-cycling activity of purified human serum albumin is significantly increased by excess free fatty acids.
Conclusion: Mishandling of Cu by albumin contributes to oxidative stress in preeclampsia. Cu chelators may represent promising mechanism-based antioxidants to attenuate oxidative stress in preeclampsia.