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- W2095200069 abstract "Plasma iron (Fe) increases after H/R and the Fe-chelator deferoxamine (Df)-starch decreases hepatic injury after H/R. However, Tf normally supplies ample binding capacity for iron in the central circulation and the benefit of Df might derive from its access to microenvironments minimally available to Tf or from changes in the binding capacity of Tf within the microcirculation. We have recently shown that H is associated with the accumulation of nitric oxide-adducts (J. Appl Physiol, 2006), which are available for the formation of peroxynitrite (Prx) during R. Tf may be particularly susceptible Prx damage due to its iron ligand structure. To address these questions we studied Fe binding to Tf in both plasma and mesenteric lymph before and after H/R. We also determined if the iron binding to Tf is altered by Prx. Animal studies used an isobaric model of H in which anesthetized rats were H to 40-50 mmHg and held at this pressure until it could no longer be maintained by blood withdrawal. They were then R with 3x shed blood volume with lactated Ringer's solution. Free-radical formation and Tf saturation with iron was assessed by electron paramagnetic resonance spectroscopy. H/R resulted in the generation of freeradicals, and an increase in Tf-Fe. However, plasma Tf was not fully saturated in plasma after H/R. By comparison, Tf was fully saturated in mesenteric lymph after H/R and this was associated with in an increase in non-Tf Fe. Tf exposed to Prx-donor SIN-1 in vitro released Fe to Df. Tf exposed to Prx also had changes in its UV-Vis absorbance spectra consistent with damage to the iron binding site. We conclude that there are substantive changes in Fe-handling after H/R and that the benefit of Df may derive from effects within the local microcirculations where Tf can be fully saturated with Fe and its binding to Fe may be altered by Prx. The results help to provide a rational framework for the development of more effective chelator therapies. Supported by DoD PRMRG 033201" @default.
- W2095200069 created "2016-06-24" @default.
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- W2095200069 date "2006-06-01" @default.
- W2095200069 modified "2023-09-28" @default.
- W2095200069 title "CHANGES IN TRANSFERRIN (Tf) AND IRON HANDLING IN HEMORRHAGE/RESUSCITATION (H/R) IN RATS" @default.
- W2095200069 doi "https://doi.org/10.1097/00024382-200606001-00162" @default.
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