Differential effects of sodium selenite in reducing tissue damage caused by three hemoglobin-based oxygen carriers

Three "blood substitutes," a diaspirin cross-linked human hemoglobin (DBBF-Hb), a bovine polymerized hemoglobin (PolyHbBv), and a human polymerized hemoglobin (O-R-PolyHbA(0)), that have undergone clinical trials are used in this study. Previously, we showed in the rat that coadministration of sodium selenite (Na(2)SeO(3)) and DBBF-Hb significantly decreased mesenteric venular leakage and epithelial disruption produced by DBBF-Hb alone but did not reduce mast cell degranulation unless given orally. The purpose of this study was to determine whether Na(2)SeO(3) produced similar beneficial responses when used with PolyHbBv and O-R-PolyHbA(0). In anesthetized Sprague-Dawley rats, the mesenteric microvasculature was perfused with PolyHbBv or O-R-PolyHbA(0), with and without Na(2)SeO(3) in the perfusate and suffusate, for 10 min, followed by FITC-albumin for 3 min, and then fixed for microscopy. Na(2)SeO(3) did not reduce leak number or area in preparations perfused with PolyHbBv and only reduced leak number (but not significantly) in preparations perfused with O-R-PolyHbA(0). Na(2)SeO(3) significantly increased mesenteric mast cell degranulation and impaired epithelial integrity in animals treated with PolyHbBv. In vitro, Na(2)SeO(3) significantly reduced the oxidation rate of DBBF-Hb in the presence of oxidants, had little effect on PolyHbBv, and increased the oxidation rate of O-R-PolyHbA(0). These results suggest that Na(2)SeO(3) moderates hemoglobin-induced damage, at least partly, through its redox interactions with the heme sites in the hemoglobin molecules studied and that accessibility of the heme site to Na(2)SeO(3) governs those interactions.