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.
Baldwin
Ann L
AL
Department of Physiology, College of Medicine, University of Arizona, Tucson, Arizona 85724-5051, USA. abaldwin@u.arizona.edu
Wiley
Elizabeth B
EB
Alayash
Abdu I
AI
D000818:Animals; D001802:Blood Substitutes / Q000633:toxicity*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D006454:Hemoglobins / Q000633:toxicity; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018038:Sodium Selenite / Q000494:pharmacology*
D001802:Blood Substitutes; D006454:Hemoglobins; D018038:Sodium Selenite