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

¹Department of Physiology, College of Medicine, University of Arizona, Tucson, Arizona 85724-5051; and ²Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892

Submitted 16 June 2003 ; accepted in final form 6 October 2003

Three "blood substitutes," a diaspirin cross-linked human hemoglobin (DBBF-Hb), a bovine polymerized hemoglobin (PolyHbBv), and a human polymerized hemoglobin (O-R-PolyHbA₀), that have undergone clinical trials are used in this study. Previously, we showed in the rat that coadministration of sodium selenite (Na₂SeO₃) 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 Na₂SeO₃ produced similar beneficial responses when used with PolyHbBv and O-R-PolyHbA₀. In anesthetized Sprague-Dawley rats, the mesenteric microvasculature was perfused with PolyHbBv or O-R-PolyHbA₀, with and without Na₂SeO₃ in the perfusate and suffusate, for 10 min, followed by FITC-albumin for 3 min, and then fixed for microscopy. Na₂SeO₃ 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-PolyHbA₀. Na₂SeO₃ significantly increased mesenteric mast cell degranulation and impaired epithelial integrity in animals treated with PolyHbBv. In vitro, Na₂SeO₃ 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-PolyHbA₀. These results suggest that Na₂SeO₃ 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 Na₂SeO₃ governs those interactions.

rat mesentery; mast cell degranulation; intestinal mucosal epithelium

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